Recent News https://biology.ucdavis.edu/articles.rss Recent News for College of Biological Sciences en Grains in the Rain: Study Opens the Door to Flood-Resistant Crops https://biology.ucdavis.edu/news/grains-rain-study-opens-door-flood-resistant-crops <span class="field field--name-title field--type-string field--label-hidden">Grains in the Rain: Study Opens the Door to Flood-Resistant Crops</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span lang="" about="/user/19386" typeof="schema:Person" property="schema:name" datatype="" content="Jules Bernstein and Greg Watry">Jules Bernstein and Greg Watry</span> </span> <span class="field field--name-created field--type-created field--label-hidden">September 19, 2019</span> <div class="field field--name-field-sf-primary-image field--type-image field--label-hidden field__item"> <img src="/sites/g/files/dgvnsk2646/files/styles/sf_landscape_16x9/public/images/article/Brady%2520and%2520Sinha.png?h=9edec8e5&amp;itok=mKmif8Vy" width="1280" height="720" alt="Siobhan Brady and Neelima Sinha" title="Associate Professor Siobhan Brady and Professor Neelima Sinha, both of the Department of Plant Biology, co-authored the study with colleagues from their labs, UC Riverside and Emory University. David Slipher/UC Davis" typeof="foaf:Image" class="image-style-sf-landscape-16x9" /> </div> <div class="addthis_toolbox addthis_default_style addthis_32x32_style" addthis:url="https://biology.ucdavis.edu/articles.rss" addthis:title="Recent News" addthis:description="Quick Summary The genes involved in flooding adaptations in plants are called submergence up-regulated families (SURFs)  In rice, these genes respond to flooding in a way that allows the food crop to thrive New research has revealed that rice share 68 SURFs with other plants, potentially opening the door to flood-resistant crops  Of the major food crops, only rice (Oryza sativa) is currently able to survive flooding. Thanks to new research, that could soon change -- good news for a world in which rains are increasing in both frequency and intensity. The research, published today in Science, shows how other crops compare to rice when submerged in water. It found that the plants – a wild-growing tomato (Solanum pennellii), the garden tomato (Solanum lycopersicum) and a plant similar to alfalfa (Medicago truncatula) – all share at least 68 families of genes with rice that are activated in response to flooding.  Rice was domesticated from wild species that grew in tropical regions, where it adapted to endure monsoons and waterlogging. Some of the genes involved in that adaptation exist in the other plants but have not evolved to switch on when the roots are flooded.  “We hope to take advantage of what we learned about rice in order to help activate the genes in other plants that could help them survive waterlogging,” said study lead Julia Bailey-Serres, a UC Riverside professor of genetics. “In the face of an unpredictable climate, we’re really focused on drought but flooding is just as bad and has devastating effects when it happens,” added study co-author Neelima Sinha, a professor of plant biology at UC Davis.  Of the major food crops, only rice (Oryza sativa) is currently able to survive flooding. IgnisSURF responses to flooding waters In the study, the team examined cells that reside at the tips of plant roots, as roots are the first responders to a flood. Root tips and shoot buds are also where a plant’s prime growing potential resides. These regions contain cells with the ability to become other types of cells in the plant. The team looked at the genes in these root tip cells to understand how they responded when flooded with water and deprived of oxygen. “We looked at the way that DNA instructs a cell to create particular stress response in a level of unprecedented detail,” said UC Riverside’s Mauricio Reynoso, one of the study’s lead researchers. “This is the first time that a flooding response has been looked at in a way that was this comprehensive, across evolutionarily different species,” added study co-author Siobhan Brady, an associate professor of plant biology at UC Davis. “Historically, people would pick one gene and say, ‘This gene is important.’ But if you look at the conserved response here, there are 68 conserved gene families that respond.”  The genes involved in flooding adaptations are called submergence up-regulated families (SURFs). “Since evolution separated the ancestors of rice and these other species as many as 180 million years ago, we did not expect to find 68 SURFs in common,” said Sinha. While UC Riverside researchers conducted flooding experiments and analysis of rice plant genomes, scientists at Davis did the same with the tomato species while the alfalfa-type plant work was done at Emory University. Though the SURFs were activated in all the plants during the flooding experiments, their genetic responses weren’t as effective as in rice. Brady noted that the genes of the garden tomato and Medicago truncatula responded to flooding in a similar way. The wild tomato, however, withered and died.  “When you try to pick it out of soil, it just crumbles,” said Brady. “It’s wet and just so mushy.”  UC Davis graduate students Donnelly West and Joel Rodriguez-Medina and postdoctoral researcher Kaisa Kajala also co-authored the study.  Preparing crops for future floods The group is now planning additional studies to improve the survival rates of the plants that currently die and rot from excess water.   This year is not the first in which excessive rains have kept farmers from being able to plant crops like corn, soybeans and alfalfa. Floods have also damaged the quality of the crops. As the climate continues to change, this trend will likely continue. Without efforts to ensure our crops adapt, the security of the world’s food supply is at risk.  “Imagine a world where kids do not have enough calories to develop,” said Bailey-Serres. “We as scientists have an urgency to help plants withstand floods, to ensure food security for the future.” The study was an international collaboration funded by the National Science Foundation’s Plant Genome Research Program. Researchers from Argentina’s National University of La Plata and Netherland’s Utrecht University participated. This article was produced in collaboration with UC Riverside.  Stay Informed! Sign up for our monthly email newsletter  “Since evolution separated the ancestors of rice and these other species as many as 180 million years ago, we did not expect to find 68 SURFs in common,” said Professor Neelima Sinha. David Slipher/UC Davis  "> <a class="addthis_button_facebook"></a> <a class="addthis_button_linkedin"></a> <script> var addthis_share = { templates: { twitter: "Of the major food crops, only rice is currently able to survive flooding. Thanks to new research, that could soon change -- good news for a world in which rains are increasing in both frequency and intensity. " } } </script> <a class="addthis_button_twitter"></a> <a class="addthis_button_email"></a> <a class="addthis_button_compact"></a> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><aside class="wysiwyg-feature-block u-width--half u-align--right"><h3 class="wysiwyg-feature-block__title">Quick Summary</h3> <div class="wysiwyg-feature-block__body"> <ul><li><strong><em>The genes involved in flooding adaptations in plants are called submergence up-regulated families (SURFs) </em></strong></li> <li><em><strong>In rice, these genes respond to flooding in a way that allows the food crop to thrive</strong></em></li> <li><strong><em>New research has revealed that rice share 68 SURFs with other plants, potentially opening the door to flood-resistant crops </em></strong></li> </ul></div> </aside><p><span><span><span>Of the major food crops, only rice (<em>Oryza sativa)</em> is currently able to survive flooding. Thanks to new research, </span></span></span><span><span><span>that could soon change -- good news for a world in which rains are increasing in both frequency and intensity.</span></span></span></p> <p><span><span><span>The research, published today in <a href="https://science.sciencemag.org/content/365/6459/1291"><em>Science</em></a>, shows how other crops compare to rice when submerged in water. It found that the plants – a wild-growing tomato (<em>Solanum pennellii</em>), the garden tomato (<em>Solanum lycopersicum</em>) and a plant similar to alfalfa (<em>Medicago truncatula</em>) – all share at least 68 families of genes with rice that are activated in response to flooding. </span></span></span></p> <p><span><span><span>Rice was domesticated from wild species that grew in tropical regions, where it adapted to endure monsoons and waterlogging. Some of the genes involved in that adaptation exist in the other plants but have not evolved to switch on when the roots are flooded. </span></span></span></p> <p><span><span><span>“We hope to take advantage of what we learned about rice in order to help activate the genes in other plants that could help them survive waterlogging,” said study lead Julia Bailey-Serres, a UC Riverside professor of genetics.</span></span></span></p> <p><span><span><span>“In the face of an unpredictable climate, we’re really focused on drought but flooding is just as bad and has devastating effects when it happens,” added study co-author Neelima Sinha, a professor of plant biology at UC Davis. </span></span></span></p> <figure role="group" class="caption caption-img align-right"><img alt="Rice" data-entity-type="file" data-entity-uuid="6b2ab443-4b27-491d-8399-b5c5924334a0" src="/sites/g/files/dgvnsk2646/files/inline-images/Rice.jpg" /><figcaption>Of the major food crops, only rice (<em>Oryza sativa)</em> is currently able to survive flooding. Ignis</figcaption></figure><h4><span><span><strong><span>SURF responses to flooding waters</span></strong></span></span></h4> <p><span><span><span>In the study, the team examined cells that reside at the tips of plant roots, as roots are the first responders to a flood. Root tips and shoot buds are also where a plant’s prime growing potential resides. These regions contain cells with the ability to become other types of cells in the plant.</span></span></span></p> <p><span><span><span>The team looked at the genes in these root tip cells to understand how they responded when flooded with water and deprived of oxygen.</span></span></span></p> <p><span><span><span>“We looked at the way that DNA instructs a cell to create particular stress response in a level of unprecedented detail,” said UC Riverside’s Mauricio Reynoso, one of the study’s lead researchers.</span></span></span></p> <p><span><span><span>“This is the first time that a flooding response has been looked at in a way that was this comprehensive, across evolutionarily different species,” added study co-author Siobhan Brady, an associate professor of plant biology at UC Davis. “Historically, people would pick one gene and say, ‘This gene is important.’ But if you look at the conserved response here, there are 68 conserved gene families that respond.” </span></span></span></p> <p><span><span><span>The genes involved in flooding adaptations are called submergence up-regulated families (SURFs). “Since evolution separated the ancestors of rice and these other species as many as 180 million years ago, we did not expect to find 68 SURFs in common,” said Sinha.</span></span></span></p> <p><span><span><span>While UC Riverside researchers conducted flooding experiments and analysis of rice plant genomes, scientists at Davis did the same with the tomato species while the alfalfa-type plant work was done at Emory University. Though the SURFs were activated in all the plants during the flooding experiments, their genetic responses weren’t as effective as in rice. Brady noted that the genes of the garden tomato and <em>Medicago truncatula</em> responded to flooding in a similar way. The wild tomato, however, withered and died. </span></span></span></p> <p><span><span><span>“When you try to pick it out of soil, it just crumbles,” said Brady. “It’s wet and just so mushy.” </span></span></span></p> <p><span><span><span>UC Davis graduate students Donnelly West and Joel Rodriguez-Medina and postdoctoral researcher Kaisa Kajala also co-authored the study. </span></span></span></p> <h4><span><span><strong><span>Preparing crops for future floods</span></strong></span></span></h4> <p><span><span><span>The group is now planning additional studies to improve the survival rates of the plants that currently die and rot from excess water.  </span></span></span></p> <p><span><span><span>This year is not the first in which excessive rains have </span><a href="https://www.post-gazette.com/business/pittsburgh-company-news/2019/07/01/Saxonburg-farmer-Al-Vettori-struggles-planting-weather-rain-harvest-agriculture-Pennsylvania/stories/201907010009"><span>kept farmers from being able to plant crops</span></a><span> like corn, soybeans and alfalfa. Floods have also damaged the quality of the crops. As the climate continues to change, this trend will likely continue. Without efforts to ensure our crops adapt, the security of the world’s food supply is at risk. </span></span></span></p> <p><span><span><span>“Imagine a world where kids do not have enough calories to develop,” said Bailey-Serres. “We as scientists have an urgency to help plants withstand floods, to ensure food security for the future.”</span></span></span></p> <p><span><span><span>The study was an international collaboration funded by the National Science Foundation’s Plant Genome Research Program. Researchers from Argentina’s National University of La Plata and Netherland’s Utrecht University participated.</span></span></span></p> <p><em><strong>This article was produced in collaboration with UC Riverside. </strong></em></p> <p class="text-align-center"><a class="btn--lg btn--primary" href="https://biology.ucdavis.edu/form/tell-us-more-about-yourself-2">Stay Informed! Sign up for our monthly email newsletter</a><span><span><span><span><span><span> </span></span></span></span></span></span></p> <figure role="group" class="caption caption-img align-center"><img alt="Neelima Sinha" data-entity-type="file" data-entity-uuid="dc3836f9-17cd-4c40-9070-510606815985" height="618" src="/sites/g/files/dgvnsk2646/files/inline-images/Neelima-Sinha-College-of-Biological-Sciences-UC-Davis.jpg" width="618" /><figcaption>“Since evolution separated the ancestors of rice and these other species as many as 180 million years ago, we did not expect to find 68 SURFs in common,” said Professor Neelima Sinha. David Slipher/UC Davis</figcaption></figure><p> </p> </div> <div class="field field--name-field-sf-article-category field--type-entity-reference field--label-above"> <div class="field__label">Category</div> <div class="field__item"><a href="/articles/food-agriculture-plants" hreflang="en">Food, Agriculture and Plant Biology</a></div> </div> <div class="field field--name-field-sf-tags field--type-entity-reference field--label-above"> <div class="field__label">Tags</div> <div class="field__items"> <div class="field__item"><a href="/tags/plant-biology-0" hreflang="en">Department of Plant Biology</a></div> <div class="field__item"><a href="/tags/genome-center" hreflang="en">Genome Center</a></div> <div class="field__item"><a href="/tags/crops" hreflang="en">crops</a></div> <div class="field__item"><a href="/tags/agriculture" hreflang="en">agriculture</a></div> <div class="field__item"><a href="/tags/climate-change" hreflang="en">climate change</a></div> <div class="field__item"><a href="/tags/genetics" hreflang="en">genetics</a></div> <div class="field__item"><a href="/tags/adaptation" hreflang="en">adaptation</a></div> <div class="field__item"><a href="/tags/evolution" hreflang="en">evolution</a></div> <div class="field__item"><a href="/tags/integrative-genetics-and-genomics-graduate-group" hreflang="en">Integrative Genetics and Genomics Graduate Group</a></div> <div class="field__item"><a href="/tags/women-stem" hreflang="en">Women in STEM</a></div> </div> </div> Thu, 19 Sep 2019 17:10:43 +0000 Jules Bernstein and Greg Watry 3466 at https://biology.ucdavis.edu Microbes Make Chemicals for Scent Marking in a Cat https://biology.ucdavis.edu/news/microbes-make-chemicals-scent-marking-cat <span class="field field--name-title field--type-string field--label-hidden">Microbes Make Chemicals for Scent Marking in a Cat </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span lang="" about="/user/5461" typeof="schema:Person" property="schema:name" datatype="">Andy Fell</span> </span> <span class="field field--name-created field--type-created field--label-hidden">September 13, 2019</span> <div class="field field--name-field-sf-primary-image field--type-image field--label-hidden field__item"> <img src="/sites/g/files/dgvnsk2646/files/styles/sf_landscape_16x9/public/images/article/gettyimages-1085400324.jpg?h=992afc23&amp;itok=DsG8mkjh" width="1280" height="720" alt="Cat" title="Cats and many other mammals use secretions from anal sacs for scent marking. A new study from UC Davis shows that these smelly compounds are made not by the cat, but by bacteria living in the anal sacs. Getty Images" typeof="foaf:Image" class="image-style-sf-landscape-16x9" /> </div> <div class="addthis_toolbox addthis_default_style addthis_32x32_style" addthis:url="https://biology.ucdavis.edu/articles.rss" addthis:title="Recent News" addthis:description=" Domestic cats, like many other mammals, use smelly secretions from anal sacs to mark territory and communicate with other animals. A new study from the Genome Center at the University of California, Davis, shows that many odiferous compounds from a male cat are actually made not by the cat, but by a community of bacteria living in the anal sacs. The work is published Sept. 13 in PLOS ONE.  “Cats use a lot of volatile chemicals for signaling, and they probably don’t make them all,” said David Coil, project scientist at the Genome Center and an author on the paper.  Many species — including cats, dogs, bears, pandas, skunks and hyenas — use anal sac secretions as a chemical language. Skunks, of course, also use them as a means of defense. The experiment grew out of the KittyBiome Project started at the Genome Center by Holly Ganz, a postdoctoral researcher working with Coil and Jonathan Eisen, professor of evolution and ecology in the UC Davis College of Biological Sciences. The KittyBiome Project has since been spun off as AnimalBiome, a company with Ganz as CEO. The researchers obtained anal sac secretions from a single male Bengal cat volunteered to participate by its owner. They extracted DNA for sequencing to identify types of bacteria, and also took samples for chemical odor analysis in Professor Cristina Davis’ laboratory in the UC Davis Department of Mechanical and Aerospace Engineering.  Sequencing showed that the microbial community was not very diverse and dominated by a small number of bacterial genera.  “There are not a lot of players there,” Coil said.  Analyzing volatile organics The most abundant bacteria from the screen were grown in culture. Mei Yamaguchi, a postdoctoral researcher in Davis’ lab, analyzed the volatile chemicals given off by the bacteria.  Davis’ lab focuses on technology for detecting and characterizing low levels of volatile organic compounds that can be markers of health and disease, from influenza in humans to citrus greening in fruit trees.  Yamaguchi and Davis were able to detect 67 volatile compounds released by the bacterial cultures. Fifty-two of these compounds were also found directly in the anal sac secretions.  The results support the idea that the bacterial community, not the cat itself, produces many of the scents used by the cat to communicate.  Coil and colleagues want to follow up by looking at more cats. If these scents are made by bacteria, why do cats smell different to each other? How do cats acquire the bacteria and do they change over life? Understanding how microbes influence their scent could have wide implications for understanding scent communication in animals.  Additional authors on the paper are Adrienne Cho, Thant Zaw and Guillaume Jospin at the UC Davis Genome Center and Mitchell McCartney at the Department of Mechanical and Aerospace Engineering. The work was partly supported by the KittyBiome Project and grants from the National Institutes of Health.  This story originally appeared on the UC Davis News website.  Media contact(s) Andy Fell, News and Media Relations, 530-752-4533, ahfell@ucdavis.edu David Coil, Genome Center, dcoil@ucdavis.edu Media Resources The KittyBiome Project Read the paper (PLOS ONE) Stay Informed! Sign up for our monthly email newsletter  "> <a class="addthis_button_facebook"></a> <a class="addthis_button_linkedin"></a> <script> var addthis_share = { templates: { twitter: "A new study from the Genome Center at the University of California, Davis, shows that many odiferous compounds from a male cat are actually made not by the cat, but by a community of bacteria living in the anal sacs. " } } </script> <a class="addthis_button_twitter"></a> <a class="addthis_button_email"></a> <a class="addthis_button_compact"></a> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><div> <div> <div> <div> <div> <p>Domestic cats, like many other mammals, use smelly secretions from anal sacs to mark territory and communicate with other animals. A new study from the Genome Center at the University of California, Davis, shows that many odiferous compounds from a male cat are actually made not by the cat, but by a community of bacteria living in the anal sacs. The work is published Sept. 13 in <a href="https://doi.org/10.1371/journal.pone.0216846"><em>PLOS ONE</em></a>. </p> <p>“Cats use a lot of volatile chemicals for signaling, and they probably don’t make them all,” said David Coil, project scientist at the Genome Center and an author on the paper. </p> <p>Many species — including cats, dogs, bears, pandas, skunks and hyenas — use anal sac secretions as a chemical language. Skunks, of course, also use them as a means of defense.</p> <p>The experiment grew out of the KittyBiome Project started at the Genome Center by Holly Ganz, a postdoctoral researcher working with Coil and Jonathan Eisen, professor of evolution and ecology in the UC Davis College of Biological Sciences. The KittyBiome Project has since been spun off as AnimalBiome, a company with Ganz as CEO.</p> <p>The researchers obtained anal sac secretions from a single male Bengal cat volunteered to participate by its owner. They extracted DNA for sequencing to identify types of bacteria, and also took samples for chemical odor analysis in Professor Cristina Davis’ laboratory in the UC Davis Department of Mechanical and Aerospace Engineering. </p> <p>Sequencing showed that the microbial community was not very diverse and dominated by a small number of bacterial genera. </p> <p>“There are not a lot of players there,” Coil said. </p> <h4>Analyzing volatile organics</h4> <p>The most abundant bacteria from the screen were grown in culture. Mei Yamaguchi, a postdoctoral researcher in Davis’ lab, analyzed the volatile chemicals given off by the bacteria. </p> <p>Davis’ lab focuses on technology for detecting and characterizing low levels of volatile organic compounds that can be markers of health and disease, from influenza in humans to citrus greening in fruit trees. </p> <p>Yamaguchi and Davis were able to detect 67 volatile compounds released by the bacterial cultures. Fifty-two of these compounds were also found directly in the anal sac secretions. </p> <p>The results support the idea that the bacterial community, not the cat itself, produces many of the scents used by the cat to communicate. </p> <p>Coil and colleagues want to follow up by looking at more cats. If these scents are made by bacteria, why do cats smell different to each other? How do cats acquire the bacteria and do they change over life? Understanding how microbes influence their scent could have wide implications for understanding scent communication in animals. </p> <p>Additional authors on the paper are Adrienne Cho, Thant Zaw and Guillaume Jospin at the UC Davis Genome Center and Mitchell McCartney at the Department of Mechanical and Aerospace Engineering. The work was partly supported by the KittyBiome Project and grants from the National Institutes of Health. </p> <p><em><strong>This story originally appeared on the <a href="https://www.ucdavis.edu/news/microbes-make-chemicals-scent-marking-in-cat">UC Davis News website</a>. </strong></em></p> </div> </div> </div> </div> </div> <div> <div> <div> <h4>Media contact(s)</h4> <p class="media-contacts"><a href="https://www.ucdavis.edu/person/articles/432">Andy Fell</a>, News and Media Relations, 530-752-4533, ahfell@ucdavis.edu</p> <p class="media-contacts"><a href="https://www.ucdavis.edu/person/articles/25989">David Coil</a>, Genome Center, dcoil@ucdavis.edu</p> </div> </div> </div> <div> <h4><span>Media</span> Resources</h4> <div> <div> <ul><li><a href="https://www.kittybiome.com/">The KittyBiome Project</a></li> <li><a href="https://doi.org/10.1371/journal.pone.0216846">Read the paper (PLOS ONE)</a></li> </ul><p class="text-align-center"><a class="btn--lg btn--primary" href="https://biology.ucdavis.edu/form/tell-us-more-about-yourself-2">Stay Informed! Sign up for our monthly email newsletter</a><span><span><span><span><span><span> </span></span></span></span></span></span></p> </div> </div> </div> </div> <div class="field field--name-field-sf-article-category field--type-entity-reference field--label-above"> <div class="field__label">Category</div> <div class="field__item"><a href="/articles/human-animal-health" hreflang="en">Human and Animal Health</a></div> </div> <div class="field field--name-field-sf-tags field--type-entity-reference field--label-above"> <div class="field__label">Tags</div> <div class="field__items"> <div class="field__item"><a href="/tags/microbiomes" hreflang="en">microbiomes</a></div> <div class="field__item"><a href="/tags/microbes" hreflang="en">microbes</a></div> <div class="field__item"><a href="/tags/genome-center" hreflang="en">Genome Center</a></div> <div class="field__item"><a href="/tags/college-engineering" hreflang="en">College of Engineering</a></div> </div> </div> Fri, 13 Sep 2019 18:25:35 +0000 Andy Fell 3456 at https://biology.ucdavis.edu VIDEO: Building Mini-Organs to Fight Pancreatic Cancer https://biology.ucdavis.edu/news/mini-organs <span class="field field--name-title field--type-string field--label-hidden">VIDEO: Building Mini-Organs to Fight Pancreatic Cancer</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span lang="" typeof="schema:Person" property="schema:name" datatype=""> (not verified)</span> </span> <span class="field field--name-created field--type-created field--label-hidden">September 10, 2019</span> <div class="field field--name-field-sf-primary-image field--type-image field--label-hidden field__item"> <img src="/sites/g/files/dgvnsk2646/files/styles/sf_landscape_16x9/public/images/article/Chang-Il-Hwang-College-of-Biological-Sciences-UC-Davis-4%5B1%5D.jpg?h=4beaf1e4&amp;itok=4GJHtmfZ" width="1280" height="720" alt="Chang-il Hwang" title="Assistant Professor Chang-il Hwang looks at a pancreatic organoid. David Slipher/UC Davis" typeof="foaf:Image" class="image-style-sf-landscape-16x9" /> </div> <div class="addthis_toolbox addthis_default_style addthis_32x32_style" addthis:url="https://biology.ucdavis.edu/articles.rss" addthis:title="Recent News" addthis:description="Assistant Professor Chang-il Hwang, Department of Microbiology and Molecular Genetics, studies pancreatic cancer, one of deadliest cancers. While it only accounts for 3 percent of cancers nationwide, 91 percent of patients succumb to the illness within five years of diagnosis. The problem is compounded because pancreatic cancer isn’t detectable until its late stages, when it’s spread to other organs. Since the pancreas is situated deep in the abdomen, tumors often escape detection, and physical symptoms usually don’t manifest until it’s too late. Learn more about Assistant Professor Hwang in his Discovering Curiosity profile When a healthy cell turns cancerous a cascade of events enables the cancer to spread throughout the body. But its origin lies within a single progenitor cell. Hwang is on the hunt to find methods to aid early cancer detection and better therapeutic treatments. Stay Informed! Sign up for our monthly email newsletter "> <a class="addthis_button_facebook"></a> <a class="addthis_button_linkedin"></a> <script> var addthis_share = { templates: { twitter: "Assistant Professor Chang-il Hwang, Department of Microbiology and Molecular Genetics, studies pancreatic cancer, one of deadliest cancers. Learn more about how Hwang and his lab colleagues are fighting pancreatic cancer with the help of organoids. " } } </script> <a class="addthis_button_twitter"></a> <a class="addthis_button_email"></a> <a class="addthis_button_compact"></a> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Assistant Professor Chang-il Hwang, Department of Microbiology and Molecular Genetics, studies pancreatic cancer, one of deadliest cancers. While it only accounts for 3 percent of cancers nationwide, 91 percent of patients succumb to the illness within five years of diagnosis. The problem is compounded because pancreatic cancer isn’t detectable until its late stages, when it’s spread to other organs. Since the pancreas is situated deep in the abdomen, tumors often escape detection, and physical symptoms usually don’t manifest until it’s too late.</p> <div class="responsive-embed" style="padding-bottom: 56.25%"><iframe width="480" height="270" src="https://www.youtube.com/embed/CEaAA9b8cuw?feature=oembed" frameborder="0" allow="accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture" allowfullscreen=""></iframe></div> <a href="https://biology.ucdavis.edu/news/discovering-curiosity-building-mini-organs-fight-pancreatic-cancer-new-faculty-chang-il-hwang" class="media-link"><div class="media-link__wrapper" data-url="https://biology.ucdavis.edu/news/discovering-curiosity-building-mini-organs-fight-pancreatic-cancer-new-faculty-chang-il-hwang"> <div class="media-link__figure"><img alt="&quot;Chang-Il Hwang" data-entity-type="file" data-entity-uuid="833dc5bb-8e17-47ef-b747-66b75b16b32b" src="/sites/g/files/dgvnsk2646/files/inline-images/Chang-Il-Hwang-College-of-Biological-Sciences-UC-Davis-Full-5.jpg" /></div> <div class="media-link__body"> <h3 class="media-link__title">Learn more about Assistant Professor Hwang in his Discovering Curiosity profile</h3> <div class="media-link__content"> <p>When a healthy cell turns cancerous a cascade of events enables the cancer to spread throughout the body. But its origin lies within a single progenitor cell. Hwang is on the hunt to find methods to aid early cancer detection and better therapeutic treatments.</p> </div> </div> </div></a> <p class="text-align-center"><a class="btn--lg btn--primary" href="https://biology.ucdavis.edu/form/tell-us-more-about-yourself-2">Stay Informed! Sign up for our monthly email newsletter</a></p> </div> <div class="field field--name-field-sf-article-category field--type-entity-reference field--label-above"> <div class="field__label">Category</div> <div class="field__item"><a href="/articles/human-animal-health" hreflang="en">Human and Animal Health</a></div> </div> <div class="field field--name-field-sf-tags field--type-entity-reference field--label-above"> <div class="field__label">Tags</div> <div class="field__items"> <div class="field__item"><a href="/tags/microbiology-and-molecular-genetics" hreflang="en">Department of Microbiology and Molecular Genetics</a></div> <div class="field__item"><a href="/tags/pancreatic-cancer" hreflang="en">pancreatic cancer</a></div> <div class="field__item"><a href="/tags/pancreas" hreflang="en">pancreas</a></div> <div class="field__item"><a href="/tags/organoids" hreflang="en">organoids</a></div> <div class="field__item"><a href="/tags/genetics" hreflang="en">genetics</a></div> <div class="field__item"><a href="/tags/mouse-biology" hreflang="en">mouse biology</a></div> <div class="field__item"><a href="/tags/video" hreflang="en">video</a></div> </div> </div> Tue, 10 Sep 2019 18:03:43 +0000 Anonymous 3446 at https://biology.ucdavis.edu A Chemical Lure That Sticks: New Trapping Methods for Citrus Greening Pest https://biology.ucdavis.edu/news/chemical-lure-sticks-new-trapping-methods-citrus-greening-pest <span class="field field--name-title field--type-string field--label-hidden">A Chemical Lure That Sticks: New Trapping Methods for Citrus Greening Pest</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span lang="" about="/user/5451" typeof="schema:Person" property="schema:name" datatype="">Greg Watry</span> </span> <span class="field field--name-created field--type-created field--label-hidden">September 09, 2019</span> <div class="field field--name-field-sf-primary-image field--type-image field--label-hidden field__item"> <img src="/sites/g/files/dgvnsk2646/files/styles/sf_landscape_16x9/public/images/article/Diaphorina-Citri-College-of-Biological-Sciences-UC-Davis.png?h=984abd09&amp;itok=rEA481f9" width="1280" height="720" alt="Asian citrus psyllid" title="The Asian citrus psyllid (Diaphorina citri) is the bogeyman of the citrus industry. Its appearance in fields is a dark harbinger for farmers, for carried within this insect is the bacteria Candidatus Liberibacter, the cause of citrus greening disease. USGS" typeof="foaf:Image" class="image-style-sf-landscape-16x9" /> </div> <div class="addthis_toolbox addthis_default_style addthis_32x32_style" addthis:url="https://biology.ucdavis.edu/articles.rss" addthis:title="Recent News" addthis:description="Quick Summary In California, around 1,100 cases of citrus greening have been found in urban orchards Walter Leal and colleagues report a new trapping method for the Asian citrus psyllid, a vector for the bacteria that causes the disease The new method combines sticky traps and an acetic acid-based chemical lure. According to the research, the trap captures 3X more male insects than naked sticky traps  The Asian citrus psyllid (Diaphorina citri) is the bogeyman of the citrus industry. Its appearance in fields is a dark harbinger for farmers, for carried within this insect is the bacteria Candidatus Liberibacter, the cause of citrus greening disease. “This is a worldwide problem,” said Distinguished Professor Walter Leal, Department of Molecular and Cellular Biology, who’s devoted his research to combating citrus greening. In Leal’s home country of Brazil, the state of São Paulo has eradicated around one-fourth of its citrus trees since 2004 in an attempt to control citrus greening outbreaks. China’s been hit with the disease, as has the United States. In California—which produced 51 percent of Unites State’s citrus during the 2018-2019 season—about 1,100 cases of citrus greening have been reported in urban orchards. “This is the most serious problem to citriculture throughout the world, because the psyllid is very effective in transmitting it from infected to non-infected plants,” said Leal. “And the bug is ‘invisible’ until the population is too high and too late to act.” While infections haven’t yet hopped to California’s commercial orchards, Leal and his colleagues aren’t waiting. In a study published in Scientific Reports, they report that an acetic acid-based, slow-release trap is capable of capturing Asian citrus psyllids even when the insect populations are low. The team worked with the pest management company ChemTica Internacional to design the sticky, chemical lure trap. “It’s very important to be able to detect these insects when they’re at low levels,” said Leal, who noted that current sticky traps (which don’t use chemical lures) aren’t very effective. During tests, the acetic acid-based trap captured on average three times more male insects than the sticky traps, which are colored yellow to attract insects. What’s more, acetic acid is a simple compound and can be found in household vinegar. “You can buy this thing by the ton, very cheap,” said Leal. “It’s very good for the farmers because the price becomes low.”    In Leal’s home country of Brazil, the state of São Paulo has forcibly eradicated around one-fourth of its citrus trees since 2004 in an attempt to control citrus greening outbreaks. David Slipher/UC DavisBetter together? During the experiments, Leal and his colleagues tested the efficacy of three different chemical attractants on Asian citrus psyllids, including formic acid, proprionic acid and acetic acid. They tested the chemicals by themselves and in various combinations. “What we do normally is when we have multiple attractants, we hope that attractants are going to synergize, so chemical A and B may be better together than A and B alone,” said Leal. “But unfortunately in this case, these compounds attract but they do no synergize with each other, so we pick the best one of them and we stick to that one.” Acetic acid, a reputed sex pheromone of the Asian citrus psyllids, won the efficacy contest. ChemTica’s slow-release chemical traps were designed to last for two weeks, the usual amount of time sticky traps last. A notable finding from the study was that acetic acid’s efficacy as an attractant was dependent on the dosage amount. “That’s one thing that I want to emphasize,” said Leal. “This is a very simple compound that we encounter in vinegar, but if you put vinegar in the field, the insects are not going to be attracted to it because there’s a certain dose that’s required to be effective.”   Citrus infected with citrus greening disease. USDA APHISNot too much, not too little According to Leal, it’s very common for chemicals to act as attractants at certain doses and as repellents at higher doses. “What seems to happen is that the insect olfactory systems get so overwhelmed with information, that they start to send the wrong information to the brain,” said Leal. “It upsets the olfactory systems in such a way that they no longer are able to respond the same.” Finding the right dosage amount required patience and meticulousness. While previous research helped Leal and his colleagues make educated guesses about what amounts to start with, the experimental process was contingent on trial and error. Leal hopes the publication of this research will help kick-start interest in acetic acid-based traps. The research was supported by the Fund for Citrus Protection. Stay Informed! Sign up for our monthly email newsletter  Leal hopes the publication of this research will help kick-start interest in acetic acid-based traps. David Slipher/UC Davis  "> <a class="addthis_button_facebook"></a> <a class="addthis_button_linkedin"></a> <script> var addthis_share = { templates: { twitter: "The Asian citrus psyllid is the bogeyman of the citrus industry. Its appearance in fields is a dark harbinger for farmers, for carried within this insect is the bacteria Candidatus Liberibacter, the cause of citrus greening disease. In a study published in Scientific Reports, UC Davis researchers report that an acetic acid-based, slow-release trap is capable of capturing Asian citrus psyllids even when the insect populations are low. " } } </script> <a class="addthis_button_twitter"></a> <a class="addthis_button_email"></a> <a class="addthis_button_compact"></a> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><aside class="wysiwyg-feature-block u-width--half u-align--right"><h3 class="wysiwyg-feature-block__title">Quick Summary</h3> <div class="wysiwyg-feature-block__body"> <ul><li><em><strong>In California, around 1,100 cases of citrus greening have been found in urban orchards</strong></em></li> <li><strong><em>Walter Leal and colleagues report a new trapping method for the Asian citrus psyllid, a vector for the bacteria that causes the disease</em></strong></li> <li><strong><em>The new method combines sticky traps and an acetic acid-based chemical lure. According to the research, the trap captures 3X more male insects than naked sticky traps </em></strong></li> </ul></div> </aside><p><span><span><span><span><span><span>The Asian citrus psyllid (<em>Diaphorina citri</em>) is the bogeyman of the citrus industry. Its appearance in fields is a dark harbinger for farmers, for </span></span></span></span></span></span><span><span><span><span><span><span>carried within this insect is the bacteria <em>Candidatus Liberibacter</em>, the cause of citrus greening disease.</span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“This is a worldwide problem,” said Distinguished Professor Walter Leal, Department of Molecular and Cellular Biology, who’s devoted his research to combating citrus greening. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>In Leal’s home country of Brazil, the state of <span><span>São Paulo</span></span> has eradicated around one-fourth of its citrus trees since 2004 in an attempt to control citrus greening outbreaks. China’s been hit with the disease, as has the United States. In California—which produced </span></span></span><a href="https://www.nass.usda.gov/Publications/Todays_Reports/reports/cfrt0819.pdf"><span><span><span>51 percent of Unites State’s citrus during the 2018-2019 season</span></span></span></a><span><span><span>—about 1,100 cases of citrus greening have been reported in urban orchards. </span></span></span></span></span></span></p> <blockquote> <p class="MsoCommentText"><span><span><span><span>“This is the most serious problem to citriculture throughout the world, because the psyllid is very effective in transmitting it from infected to non-infected plants,” said Leal. “And the bug is ‘invisible’ until the population is too high and too late to act.”</span></span></span></span></p> </blockquote> <p><span><span><span><span><span><span>While infections haven’t yet hopped to California’s commercial orchards, Leal and his colleagues aren’t waiting. In a study published in </span></span></span><a href="https://www.nature.com/articles/s41598-019-49469-3"><em><span><span><span>Scientific Reports</span></span></span></em></a><em><span><span><span>,</span></span></span></em><span><span><span> they report that an acetic acid-based, slow-release trap is capable of capturing Asian citrus psyllids even when the insect populations are low. The team worked with the pest management company ChemTica Internacional to design the sticky, chemical lure trap. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“It’s very important to be able to detect these insects when they’re at low levels,” said Leal, who noted that current sticky traps (which don’t use chemical lures) aren’t very effective.</span></span></span></span></span></span></p> <p><span><span><span><span><span><span>During tests, the acetic acid-based trap captured on average three times more male insects than the sticky traps, which are colored yellow to attract insects. What’s more, acetic acid is a simple compound and can be found in household vinegar. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“You can buy this thing by the ton, very cheap,” said Leal. “It’s very good for the farmers because the price becomes low.”   </span></span></span></span></span></span></p> <figure role="group" class="caption caption-img"><img alt="Walter Leal" data-entity-type="file" data-entity-uuid="be94df15-18a5-4162-b0c5-d1b5731b3d7d" src="/sites/g/files/dgvnsk2646/files/inline-images/Walter-Leal-College-of-Biologcial-Sciences-1.png" /><figcaption>In Leal’s home country of Brazil, the state of São Paulo has forcibly eradicated around one-fourth of its citrus trees since 2004 in an attempt to control citrus greening outbreaks. David Slipher/UC Davis</figcaption></figure><h4><span><span><span><strong><span><span><span>Better together? </span></span></span></strong></span></span></span></h4> <p><span><span><span><span><span><span>During the experiments, Leal and his colleagues tested the efficacy of three different chemical attractants on Asian citrus psyllids, including formic acid, proprionic acid and acetic acid. They tested the chemicals by themselves and in various combinations. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“What we do normally is when we have multiple attractants, we hope that attractants are going to synergize, so chemical A and B may be better together than A and B alone,” said Leal. “But unfortunately in this case, these compounds attract but they do no synergize with each other, so we pick the best one of them and we stick to that one.”</span></span></span></span></span></span></p> <p><span><span><span><span><span><span>Acetic acid, a reputed sex pheromone of the Asian citrus psyllids, won the efficacy contest. ChemTica’s slow-release chemical traps were designed to last for two weeks, the usual amount of time sticky traps last. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>A notable finding from the study was that acetic acid’s efficacy as an attractant was dependent on the dosage amount. </span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“That’s one thing that I want to emphasize,” said Leal. “This is a very simple compound that we encounter in vinegar, but if you put vinegar in the field, the insects are not going to be attracted to it because there’s a certain dose that’s required to be effective.”  </span></span></span></span></span></span></p> </blockquote> <figure role="group" class="caption caption-img"><img alt="Citrus" data-entity-type="file" data-entity-uuid="3eb266a8-0e24-424b-8b57-0728f96efdb4" src="/sites/g/files/dgvnsk2646/files/inline-images/CitrusGreening1.jpg" /><figcaption>Citrus infected with citrus greening disease. USDA APHIS</figcaption></figure><h4><span><span><span><strong><span><span><span>Not too much, not too little</span></span></span></strong></span></span></span></h4> <p><span><span><span><span><span><span>According to Leal, it’s very common for chemicals to act as attractants at certain doses and as repellents at higher doses. </span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“What seems to happen is that the insect olfactory systems get so overwhelmed with information, that they start to send the wrong information to the brain,” said Leal. “It upsets the olfactory systems in such a way that they no longer are able to respond the same.” </span></span></span></span></span></span></p> </blockquote> <p><span><span><span><span><span><span>Finding the right dosage amount required patience and meticulousness. While previous research helped Leal and his colleagues make educated guesses about what amounts to start with, the experimental process was contingent on trial and error. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>Leal hopes the publication of this research will help kick-start interest in acetic acid-based traps. The research was supported by the Fund for Citrus Protection.</span></span></span></span></span></span></p> <p class="text-align-center"><a class="btn--lg btn--primary" href="https://biology.ucdavis.edu/form/tell-us-more-about-yourself-2">Stay Informed! Sign up for our monthly email newsletter</a><span><span><span><span><span><span> </span></span></span></span></span></span></p> <figure role="group" class="caption caption-img"><img alt="Leal in the lab" data-entity-type="file" data-entity-uuid="a13babd3-857c-49d4-a0ce-858bb722df83" src="/sites/g/files/dgvnsk2646/files/inline-images/Walter-Leal-College-of-Biologcial-Sciences-3.png" /><figcaption>Leal hopes the publication of this research will help kick-start interest in acetic acid-based traps. David Slipher/UC Davis</figcaption></figure><p> </p> </div> <div class="field field--name-field-sf-article-category field--type-entity-reference field--label-above"> <div class="field__label">Category</div> <div class="field__item"><a href="/articles/food-agriculture-plants" hreflang="en">Food, Agriculture and Plant Biology</a></div> </div> <div class="field field--name-field-sf-tags field--type-entity-reference field--label-above"> <div class="field__label">Tags</div> <div class="field__items"> <div class="field__item"><a href="/tags/molecular-and-cellular-biology" hreflang="en">Department of Molecular and Cellular Biology</a></div> <div class="field__item"><a href="/tags/insects" hreflang="en">insects</a></div> <div class="field__item"><a href="/tags/agriculture" hreflang="en">agriculture</a></div> <div class="field__item"><a href="/tags/ecology" hreflang="en">ecology</a></div> <div class="field__item"><a href="/tags/fruits" hreflang="en">fruits</a></div> <div class="field__item"><a href="/tags/citrus" hreflang="en">citrus</a></div> <div class="field__item"><a href="/tags/citrus-greening-disease" hreflang="en">citrus greening disease</a></div> <div class="field__item"><a href="/tags/pests" hreflang="en">pests</a></div> <div class="field__item"><a href="/tags/olfaction" hreflang="en">olfaction</a></div> </div> </div> Mon, 09 Sep 2019 22:12:05 +0000 Greg Watry 3441 at https://biology.ucdavis.edu Chloroplasts, β-Barrel Proteins and Traversing through Graduate School https://biology.ucdavis.edu/news/chloroplasts-b-barrel-proteins-and-traversing-through-graduate-school <span class="field field--name-title field--type-string field--label-hidden">Chloroplasts, β-Barrel Proteins and Traversing through Graduate School</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span lang="" about="/user/5616" typeof="schema:Person" property="schema:name" datatype="">Ann Filmer</span> </span> <span class="field field--name-created field--type-created field--label-hidden">September 09, 2019</span> <div class="field field--name-field-sf-primary-image field--type-image field--label-hidden field__item"> <img src="/sites/g/files/dgvnsk2646/files/styles/sf_landscape_16x9/public/images/article/Philip-Day-Theg-Lab-College-of-Biological-Sciences-UC-Davis-8.jpg?h=2d36e1ed&amp;itok=alRgxAIm" width="1280" height="720" alt="Philip Day and Steven Theg " title="This story of how a graduate student and his two major professors made a significant find didn’t follow a straightforward path. David Slipher/UC Davis" typeof="foaf:Image" class="image-style-sf-landscape-16x9" /> </div> <div class="addthis_toolbox addthis_default_style addthis_32x32_style" addthis:url="https://biology.ucdavis.edu/articles.rss" addthis:title="Recent News" addthis:description="In a new publication in The Plant Cell — “Chloroplast Outer Membrane β-Barrel Proteins Use Components of the General Import Apparatus” — authors Philip Day, Steven Theg, and Kentaro Inoue, all at University of California, Davis, determined how β-barrel proteins are sorted to the correct location in plant chloroplast envelopes, which have two membranes. Chloroplasts, which are responsible for photosynthesis in plants, evolved about a billion years ago from an ancient endosymbiotic relationship between a cyanobacteria species and a eukaryotic cell. This story of how a graduate student and his two major professors made a significant find didn’t follow a straightforward path. It ended up being a testament to great research, resilience, perseverance, and keen mentoring. “In both my labs at UC Davis — Steven Theg’s lab, and Kentaro Inoue’s lab — everybody was really interested in how proteins are correctly sorted to different places within the chloroplast,” said Philip Day, who co-published this paper just as he was finishing his Ph.D. at UC Davis. Theg and Inoue both served as Day’s major professors. “The chloroplast is a complex structure,” added Day. “It has two envelope membranes, and a thylakoid membrane, and in between all of these membranes there are aqueous areas. To get the proteins to their specified locations, there are a lot of signals and machinery needed to make this happen, which is what we’re trying to understand.” Day’s work was about a very specific type of protein — β-barrel proteins, which are inserted into biological membranes. This type of protein is found only in a few other types of organism membranes, including bacteria outer membranes and mitochondria outer membranes. He and his major professors had to figure out how the β-barrels, which are transmembrane proteins, are specifically sorted to the chloroplast outer membrane. Switching Professors Midway through a Ph.D. Program Philip Day started as a graduate student in the Plant Biology Graduate Group at UC Davis in 2012, and joined Kentaro Inoue’s research lab in the Department of Plant Sciences in 2013. Day was making headway in his research, when Kentaro Inoue, his major professor who was an avid bicyclist and known for his sense of humor, was tragically killed in a bike accident in 2016. Kentaro Inoue, Department of Plant Sciences, UC Davis. (courtesy photo)The loss of Inoue, who was originally from Japan, was felt across UC Davis and by his many global colleagues. Within Inoue’s lab, three graduate students (Philip Day, Lucas Mckinnon, and Laura Klasek), all working on chloroplasts, were suddenly adrift following the loss of their major professor. Steven Theg, a professor in the Department of Plant Biology at UC Davis, who also works on protein translocation across chloroplast membranes, stepped in to see how he could help with Inoue’s graduate students and their research. “I already knew the research that Philip was doing with Kentaro,” said Theg. “Through our shared interests we knew each other’s students and research quite well. At the time, I already had a full load of graduate students, but when Kentaro passed away so unexpectedly, it made complete sense for them to join my group. “Not only were they doing important work, but this was a critical time during their graduate studies. I hoped that if his students joined my group, we could continue Kentaro’s research with a minimum of interruption. This would be Kentaro’s legacy.&quot; It was only possible to do this with the commitment from Plant Sciences chairs Joe DiTomaso, and later, Gail Taylor, along with Dee Madderra, to continue their departmental student support until they graduated. Day notes that the switch to Steve Theg as a major professor went as smoothly as could be expected at a time of sadness and upheaval, and that he will forever be grateful to Theg for helping him and his two graduate student colleagues continue their original research. Philip Day started as a graduate student in the Plant Biology Graduate Group at UC Davis in 2012, and joined Kentaro Inoue’s research lab in the Department of Plant Sciences in 2013. David Slipher/UC DavisWhy Chloroplasts? “The evolutionary history of chloroplasts is one area I wanted to explore when I started graduate school at UC Davis,” said Day. “As an undergrad at University of Nebraska, I learned about this theory of endosymbiosis, and about how both chloroplasts and mitochondria arose from bacteria that basically took up residence inside of a eukaryotic cell. That just blew my mind, and I set my sights on doing graduate research on chloroplasts.” He stuck with his plan and succeeded quite well. “What I’m proudest about in this research is my work on the OEP80 protein,” said Day. “It uses a transit peptide, which is uncommon for outer membrane proteins and was unexpected. That was one of the first discoveries that I made, and it’s included in this paper.” In imagining how his current work on β-barrel proteins might one day have application, Day said that just about everything we learn in biology could have different sorts of application, or uses beyond our present understanding. “β-barrel proteins, found on the outside of bacteria, might be good targets for vaccine production,” said Day. “In chloroplasts, people can express bacterial proteins, which they can use to make vaccines, so they don’t have to make a vaccine using the pathogen. They can take the protein and accumulate it in plant cells.” Looking ahead, Day says that a possible application of his research would be to produce bacterial or pathogen β-barrels in plant cells.  Moving Forward Philip Day left UC Davis this summer, after completing his Ph.D. with Professor Theg. He moved north to Pullman, Washington to take a postdoctoral research position with Professor Henning Kunz at Washington State University. Day will continue working on chloroplast research there, moving beyond his research at UC Davis. “What I did in my Ph.D. was mostly about how these proteins are sorted to the correct location,” said Day. “For my postdoc, I’ll be working on the chloroplast and the chloroplast envelope which has two membranes, and how ions and other solutes are transported through the envelopes. “During my graduate studies at UC Davis, I became a better scientist and gained a passion for studying plant cells and plant biochemistry due to the mentoring of both professors, Kentaro Inoue and Steve Theg. This experience opened the path for me to continue researching chloroplasts and grow as a scientist.” Added Professor Theg, “With his Ph.D. work, Philip has added important missing information about chloroplasts, not only concerning their biogenesis and maintenance, but their evolution as well. I expect his paper will be widely read and cited by our colleagues around the world who are interested in this essential plant organelle.” Contacts: Philip Day, Department of Molecular Plant Sciences, Washington State University, philip.day@wsu.edu Steven Theg, Department of Plant Biology, UC Davis, smtheg@ucdavis.edu Ann Filmer, Communications, Department of Plant Sciences, UC Davis, afilmer@ucdavis.edu (Article by Ann Filmer, Department of Plant Sciences, UC Davis. Photos by David Slipher, College of Biological Sciences, UC Davis.) This article originally appeared on the Department of Plant Sciences website.  Stay Informed! Sign up for our monthly email newsletter  “During my graduate studies at UC Davis, I became a better scientist and gained a passion for studying plant cells and plant biochemistry due to the mentoring of both professors, Kentaro Inoue and Steve Theg,&quot; said Day. David Slipher/UC Davis  "> <a class="addthis_button_facebook"></a> <a class="addthis_button_linkedin"></a> <script> var addthis_share = { templates: { twitter: "In a new publication in The Plant Cell — “Chloroplast Outer Membrane β-Barrel Proteins Use Components of the General Import Apparatus” — authors Philip Day, Steven Theg, and Kentaro Inoue, all at University of California, Davis, determined how β-barrel proteins are sorted to the correct location in plant chloroplast envelopes, which have two membranes. " } } </script> <a class="addthis_button_twitter"></a> <a class="addthis_button_email"></a> <a class="addthis_button_compact"></a> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p><span><span><span>In a new publication in <a href="http://www.plantcell.org/content/31/8/1845"><em>The Plant Cell</em></a> — “Chloroplast Outer Membrane β-Barrel Proteins Use Components of the General Import Apparatus” — authors Philip Day, Steven Theg, and Kentaro Inoue, all at University of California, Davis, determined how β-barrel proteins are sorted to the correct location in plant chloroplast envelopes, which have two membranes. Chloroplasts, which are responsible for photosynthesis in plants, evolved about a billion years ago from an ancient endosymbiotic relationship between a cyanobacteria species and a eukaryotic cell.</span></span></span></p> <p><span><span><span>This story of how a graduate student and his two major professors made a significant find didn’t follow a straightforward path. It ended up being a testament to great research, resilience, perseverance, and keen mentoring.</span></span></span></p> <p><span><span><span>“In both my labs at UC Davis — Steven Theg’s lab, and Kentaro Inoue’s lab — everybody was really interested in how proteins are correctly sorted to different places within the chloroplast,” said Philip Day, who co-published this paper just as he was finishing his Ph.D. at UC Davis. Theg and Inoue both served as Day’s major professors.</span></span></span></p> <blockquote> <p><span><span><span>“The chloroplast is a complex structure,” added Day. “It has two envelope membranes, and a thylakoid membrane, and in between all of these membranes there are aqueous areas. To get the proteins to their specified locations, there are a lot of signals and machinery needed to make this happen, which is what we’re trying to understand.”</span></span></span></p> </blockquote> <p><span><span><span>Day’s work was about a very specific type of protein — β-barrel proteins, which are inserted into biological membranes. This type of protein is found only in a few other types of organism membranes, including bacteria outer membranes and mitochondria outer membranes. He and his major professors had to figure out how the β-barrels, which are transmembrane proteins, are specifically sorted to the chloroplast outer membrane.</span></span></span></p> <h4><span><span><span><strong><span>Switching Professors Midway through a Ph.D. Program</span></strong></span></span></span></h4> <p><span><span><span>Philip Day started as a graduate student in the <a href="https://pbi.ucdavis.edu/">Plant Biology Graduate Group</a> at UC Davis in 2012, and joined Kentaro Inoue’s research lab in the <a href="https://www.plantsciences.ucdavis.edu/">Department of Plant Sciences</a> in 2013. Day was making headway in his research, when <a href="https://www.plantsciences.ucdavis.edu/news/kentaro-inoue-killed-bicycle-accident">Kentaro Inoue</a>, his major professor who was an avid bicyclist and known for his sense of humor, was tragically killed in a bike accident in 2016.</span></span></span></p> <figure role="group" class="caption caption-img align-right"><img alt="Kentaro Inoue" data-entity-type="file" data-entity-uuid="9fe56196-e222-4b76-be73-cdb72e731ab0" height="351" src="/sites/g/files/dgvnsk2646/files/inline-images/0299.09c%2520339px%2520cropped.png" width="291" /><figcaption>Kentaro Inoue, Department of Plant Sciences, UC Davis. (courtesy photo)</figcaption></figure><p><span><span><span>The loss of Inoue, who was originally from Japan, was felt across UC Davis and by his many </span></span></span><span><span><span>global colleagues. Within Inoue’s lab, three graduate students (Philip Day, Lucas Mckinnon, and Laura Klasek), all working on chloroplasts, were suddenly adrift following the loss of their major professor.</span></span></span></p> <p><span><span><span><a href="https://biology.ucdavis.edu/people/steven-theg">Steven Theg</a>, a professor in the <a href="http://www-plb.ucdavis.edu/">Department of Plant Biology</a> at UC Davis, who also works on protein translocation across chloroplast membranes, stepped in to see how he could help with Inoue’s graduate students and their research.</span></span></span></p> <p><span><span><span>“I already knew the research that Philip was doing with Kentaro,” said Theg. “Through our shared interests we knew each other’s students and research quite well. At the time, I already had a full load of graduate students, but when Kentaro passed away so unexpectedly, it made complete sense for them to join my group.</span></span></span></p> <blockquote> <p><span><span><span>“Not only were they doing important work, but this was a critical time during their graduate studies. I hoped that if his students joined my group, we could continue Kentaro’s research with a minimum of interruption. This would be Kentaro’s legacy."</span></span></span></p> </blockquote> <p><span><span><span>It was only possible to do this with the commitment from Plant Sciences chairs <a href="https://www.plantsciences.ucdavis.edu/people/joseph-ditomaso">Joe DiTomaso</a>, and later, <a href="https://www.plantsciences.ucdavis.edu/people/gail-taylor">Gail Taylor</a>, along with <a href="https://www.plantsciences.ucdavis.edu/people/deidra-madderra">Dee Madderra</a>, to continue their departmental student support until they graduated.</span></span></span></p> <p><span><span><span>Day notes that the switch to Steve Theg as a major professor went as smoothly as could be expected at a time of sadness and upheaval, and that he will forever be grateful to Theg for helping him and his two graduate student colleagues continue their original research.</span></span></span></p> <figure role="group" class="caption caption-img"><img alt="Philip Day" data-entity-type="file" data-entity-uuid="1eba1b29-f6d9-46a1-8d2b-ef38c92bc0d6" src="/sites/g/files/dgvnsk2646/files/inline-images/Philip-Day-Theg-Lab-College-of-Biological-Sciences-UC-Davis-11.jpg" /><figcaption>Philip Day started as a graduate student in the <a href="https://pbi.ucdavis.edu/">Plant Biology Graduate Group</a> at UC Davis in 2012, and joined Kentaro Inoue’s research lab in the <a href="https://www.plantsciences.ucdavis.edu/">Department of Plant Sciences</a> in 2013. David Slipher/UC Davis</figcaption></figure><h4><span><span><span><strong><span>Why Chloroplasts?</span></strong></span></span></span></h4> <p><span><span><span>“The evolutionary history of chloroplasts is one area I wanted to explore when I started graduate school at UC Davis,” said Day. “As an undergrad at University of Nebraska, I learned about this theory of endosymbiosis, and about how both chloroplasts and mitochondria arose from bacteria that basically took up residence inside of a eukaryotic cell. That just blew my mind, and I set my sights on doing graduate research on chloroplasts.”</span></span></span></p> <p><span><span><span>He stuck with his plan and succeeded quite well. </span></span></span></p> <blockquote> <p><span><span><span>“What I’m proudest about in this research is my work on the OEP80 protein,” said Day. “It uses a transit peptide, which is uncommon for outer membrane proteins and was unexpected. That was one of the first discoveries that I made, and it’s included in this paper.”</span></span></span></p> </blockquote> <p><span><span><span>In imagining how his current work on β-barrel proteins might one day have application, Day said that just about everything we learn in biology could have different sorts of application, or uses beyond our present understanding.</span></span></span></p> <p><span><span><span>“β-barrel proteins, found on the outside of bacteria, might be good targets for vaccine production,” said Day. “In chloroplasts, people can express bacterial proteins, which they can use to make vaccines, so they don’t have to make a vaccine using the pathogen. They can take the protein and accumulate it in plant cells.”</span></span></span></p> <p><span><span><span>Looking ahead, Day says that a possible application of his research would be to produce bacterial or pathogen β-barrels in plant cells. </span></span></span></p> <p><span><span><span><img alt="Plants" data-entity-type="file" data-entity-uuid="cb785686-59a3-4852-a9ac-d4ed60cd78a4" src="/sites/g/files/dgvnsk2646/files/inline-images/Philip-Day-Theg-Lab-College-of-Biological-Sciences-UC-Davis-10.jpg" /></span></span></span></p> <h4><span><span><span><strong><span>Moving Forward</span></strong></span></span></span></h4> <p><span><span><span>Philip Day left UC Davis this summer, after completing his Ph.D. with Professor Theg. He moved north to Pullman, Washington to take a postdoctoral research position with Professor <a href="https://mps.wsu.edu/dr-hans-henning-kunz/">Henning Kunz</a> at Washington State University. Day will continue working on chloroplast research there, moving beyond his research at UC Davis.</span></span></span></p> <p><span><span><span>“What I did in my Ph.D. was mostly about how these proteins are sorted to the correct location,” said Day. “For my postdoc, I’ll be working on the chloroplast and the chloroplast envelope which has two membranes, and how ions and other solutes are transported through the envelopes.</span></span></span></p> <blockquote> <p><span><span><span>“During my graduate studies at UC Davis, I became a better scientist and gained a passion for studying plant cells and plant biochemistry due to the mentoring of both professors, Kentaro Inoue and Steve Theg. This experience opened the path for me to continue researching chloroplasts and grow as a scientist.”</span></span></span></p> </blockquote> <p><span><span><span>Added Professor Theg, “With his Ph.D. work, Philip has added important missing information about chloroplasts, not only concerning their biogenesis and maintenance, but their evolution as well. I expect his paper will be widely read and cited by our colleagues around the world who are interested in this essential plant organelle.”</span></span></span></p> <h4><span><span><span><strong><span>Contacts:</span></strong></span></span></span></h4> <ul><li><span><span><span>Philip Day, Department of Molecular Plant Sciences, Washington State University, <a href="mailto:philip.day@wsu.edu">philip.day@wsu.edu</a> </span></span></span></li> <li><span><span><span>Steven Theg, Department of Plant Biology, UC Davis, <a href="mailto:smtheg@ucdavis.edu">smtheg@ucdavis.edu</a> </span></span></span></li> <li><span><span><span>Ann Filmer, Communications, Department of Plant Sciences, UC Davis, <a href="mailto:afilmer@ucdavis.edu">afilmer@ucdavis.edu</a> </span></span></span></li> </ul><p><span><span><span>(<em>Article by </em><a href="https://www.plantsciences.ucdavis.edu/people/ann-filmer"><em>Ann Filmer</em></a><em>, Department of Plant Sciences, UC Davis. Photos by </em><a href="https://biology.ucdavis.edu/people/david-slipher"><em>David Slipher</em></a><em>, College of Biological Sciences, UC Davis.</em>)</span></span></span></p> <p><em><strong>This article originally appeared on the<a href="https://www.plantsciences.ucdavis.edu/news/chloroplasts-b-barrel-proteins-and-traversing-through-graduate-school"> Department of Plant Sciences website</a>. </strong></em></p> <p class="text-align-center"><a class="btn--lg btn--primary" href="https://biology.ucdavis.edu/form/tell-us-more-about-yourself-2">Stay Informed! Sign up for our monthly email newsletter</a><span><span><span><span><span><span> </span></span></span></span></span></span></p> <figure role="group" class="caption caption-img"><img alt="Philip Day" data-entity-type="file" data-entity-uuid="7ece7f34-bfef-4487-aeec-2673130caaf8" src="/sites/g/files/dgvnsk2646/files/inline-images/Philip-Day-Theg-Lab-College-of-Biological-Sciences-UC-Davis-9.jpg" /><figcaption>“During my graduate studies at UC Davis, I became a better scientist and gained a passion for studying plant cells and plant biochemistry due to the mentoring of both professors, Kentaro Inoue and Steve Theg," said Day. David Slipher/UC Davis</figcaption></figure><p> </p> </div> <div class="field field--name-field-sf-article-category field--type-entity-reference field--label-above"> <div class="field__label">Category</div> <div class="field__item"><a href="/articles/food-agriculture-plants" hreflang="en">Food, Agriculture and Plant Biology</a></div> </div> <div class="field field--name-field-sf-tags field--type-entity-reference field--label-above"> <div class="field__label">Tags</div> <div class="field__items"> <div class="field__item"><a href="/tags/plant-biology-0" hreflang="en">Department of Plant Biology</a></div> <div class="field__item"><a href="/tags/chloroplasts" hreflang="en">chloroplasts</a></div> <div class="field__item"><a href="/tags/chlorophyll" hreflang="en">chlorophyll</a></div> <div class="field__item"><a href="/tags/graduate-student-news" hreflang="en">Graduate Student News</a></div> <div class="field__item"><a href="/tags/plant-biology-graduate-group" hreflang="en">Plant Biology Graduate Group</a></div> </div> </div> Mon, 09 Sep 2019 15:39:53 +0000 Ann Filmer 3436 at https://biology.ucdavis.edu Remembering Kendra Chan https://biology.ucdavis.edu/news/chancellors-statement-kendra-chan-0 <span class="field field--name-title field--type-string field--label-hidden">Remembering Kendra Chan</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span lang="" typeof="schema:Person" property="schema:name" datatype=""> (not verified)</span> </span> <span class="field field--name-created field--type-created field--label-hidden">September 04, 2019</span> <div class="field field--name-field-sf-primary-image field--type-image field--label-hidden field__item"> <img src="/sites/g/files/dgvnsk2646/files/styles/sf_landscape_16x9/public/images/article/IMG_5942.JPG?h=c673cd1c&amp;itok=sm0cnQbD" width="1280" height="720" alt="Chancellor Gary May " title="Chancellor Gary S. May. UC Davis" typeof="foaf:Image" class="image-style-sf-landscape-16x9" /> </div> <div class="addthis_toolbox addthis_default_style addthis_32x32_style" addthis:url="https://biology.ucdavis.edu/articles.rss" addthis:title="Recent News" addthis:description=" Chancellor Gary S. May issued the following statement today (Sept. 4): ChanWe have learned that Kendra Chan, a UC Davis alumna, and her father Raymond “Scott” Chan, of Los Altos, were among the victims of the tragic Conception dive boat fire off the coast of Southern California. Our entire UC Davis community mourns with their family and friends.  Kendra’s fascination with marine ecology will continue to inspire everyone she touched. She pursued her scientific curiosity with great zest at UC Davis, from working at our Bodega Marine Lab for two summers to studying biodiversity in the Stachowicz Lab. As the co-president of Davis SEEDS, she supported fellow students in making the transition from college to career. Kendra made her mark at UC Davis. We are grateful for her contributions to our campus community and her dedication to creating a healthier planet. We will remember her. Learn more about Kendra Chan and her impact on UC Davis.  Media contact(s) Melissa Blouin, News and Media Relations, 530-752-2542, cell 530-564-2698, mlblouin@ucdavis.edu This post originally appeared on the UC Davis website.  "> <a class="addthis_button_facebook"></a> <a class="addthis_button_linkedin"></a> <script> var addthis_share = { templates: { twitter: "Chancellor Gary S. May issued the following statement on Kendra Chan, a UC Davis alumna, and her father Raymond “Scott” Chan, of Los Altos, who were among the victims of the tragic Conception dive boat fire off the coast of Southern California. " } } </script> <a class="addthis_button_twitter"></a> <a class="addthis_button_email"></a> <a class="addthis_button_compact"></a> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><div class="responsive-embed" style="padding-bottom: 56.25%"><iframe width="480" height="270" src="https://www.youtube.com/embed/zPz5lbVengU?feature=oembed" frameborder="0" allow="accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture" allowfullscreen=""></iframe></div> <p><em>Chancellor Gary S. May issued the following statement today (Sept. 4):</em></p> <figure role="group" class="caption caption-img align-right"><img alt="Kendra Chan" data-entity-type="file" data-entity-uuid="5e8cd11a-a6e6-465d-912f-13f58bf65988" src="/sites/g/files/dgvnsk2646/files/inline-images/Kendra.jpg" /><figcaption>Chan</figcaption></figure><p>We have learned that Kendra Chan, a UC Davis alumna, and her father Raymond “Scott” Chan, of Los Altos, were among the victims of the tragic Conception dive boat fire off the coast of Southern California. Our entire UC Davis community mourns with their family and friends. </p> <p>Kendra’s fascination with marine ecology will continue to inspire everyone she touched. She pursued her scientific curiosity with great zest at UC Davis, from working at our Bodega Marine Lab for two summers to studying biodiversity in the Stachowicz Lab. As the co-president of Davis SEEDS, she supported fellow students in making the transition from college to career.</p> <p>Kendra made her mark at UC Davis. We are grateful for her contributions to our campus community and her dedication to creating a healthier planet. We will remember her.</p> <p><a href="https://www.ucdavis.edu/news/memoriam-margery-magill-kendra-chan/">Learn more about Kendra Chan and her impact on UC Davis</a>. </p> <h2>Media contact(s)</h2> <p><a href="https://www.ucdavis.edu/person/articles/24853">Melissa Blouin</a>, News and Media Relations, 530-752-2542, cell 530-564-2698, mlblouin@ucdavis.edu</p> <p><em><strong>This post originally appeared on the <a href="https://www.ucdavis.edu/news/chancellors-statement-kendra-chan">UC Davis website</a>. </strong></em></p> </div> <div class="field field--name-field-sf-article-category field--type-entity-reference field--label-above"> <div class="field__label">Category</div> <div class="field__item"><a href="/articles/campus-community" hreflang="en">Campus and Community</a></div> </div> Thu, 05 Sep 2019 00:52:40 +0000 Anonymous 3431 at https://biology.ucdavis.edu Ancient Splices of Biology: Tracing the Evolution of Insect Sexual Development https://biology.ucdavis.edu/news/ancient-splices-biology-tracing-evolution-insect-sexual-development <span class="field field--name-title field--type-string field--label-hidden">Ancient Splices of Biology: Tracing the Evolution of Insect Sexual Development </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span lang="" about="/user/5451" typeof="schema:Person" property="schema:name" datatype="">Greg Watry</span> </span> <span class="field field--name-created field--type-created field--label-hidden">September 04, 2019</span> <div class="field field--name-field-sf-primary-image field--type-image field--label-hidden field__item"> <img src="/sites/g/files/dgvnsk2646/files/styles/sf_landscape_16x9/public/images/article/German-Cockroach-College-of-Biologcial-Sciences-UC-Davis.jpg?h=266a183a&amp;itok=0cH1sGX3" width="1280" height="720" alt="German cockroach" title="In the study, the researchers studied three hemimetabolous insect species: the kissing bug, the louse and the German cockroach (pictured). Pixabay " typeof="foaf:Image" class="image-style-sf-landscape-16x9" /> </div> <div class="addthis_toolbox addthis_default_style addthis_32x32_style" addthis:url="https://biology.ucdavis.edu/articles.rss" addthis:title="Recent News" addthis:description="Quick Summary Unlike sexual development in vertebrates, like mammals and fish, insects use an RNA splicing-based mode of sexual development In a study appearing in eLife, UC Davis researchers trace this sexual development strategy to hemimetabolous insect orders, or those that develop from larvae to adults without a pupal stage The team studied three hemimetabolous insect species: the kissing bug (Rhodnius prolixus), the louse (Pediculus humanus) and the German cockroach (Blattella germanica) Sexual determination and differentiation work in myriad ways across the animal kingdom. In vertebrates, like mammals and fish, sexual determination leads to the development of either ovaries or testis. These organs then secrete hormones that go on to govern the sexual development of the rest of the organism’s body. Insects are a completely different beast. “The way that insects develop male versus female characteristics is using different kinds of RNA splicing and processing,” said Judy Wexler, who graduated from UC Davis in 2018 with a Ph.D. in Population Biology. “The same genes are used to direct male development or female development; it’s just how those genes and RNA are processed that will tell a cell, ‘You’re a male cell, or you’re a female cell.’” According to Wexler, insects are the only known animal to perform sexual determination and differentiation via this toggle-like system, which makes use of the biological phenomenon known as “alternative splicing.” Even their closest arthropod relatives, crustaceans, don’t use this sexual development strategy. So it begs the question, how old is the splicing-based mode of sexual differentiation?  “It really is radically different from the way other animal groups manage their sexual differentiation,” said Professor Artyom Kopp, Department of Evolution and Ecology and director of the Center for Population Biology. “The canonical insect sex pathway is in every developmental biology textbook, but nobody has ever looked at how that pathway came about.” In a study appearing in eLife, Wexler and her colleagues, including Kopp, trace this splicing-based sexual development strategy to hemimetabolous insect orders, or those that develop from larvae to adults without a pupal stage. These types of insects are more ancient than holometabolous insects, which have a pupal stage.   “The main finding from all of the insects we studied is that together, they represent an intermediate state between what we know to be true in crustaceans and then what we know to be true about sexual development in holometabolous insects,” said Wexler. “These three hemimetabolous insects we studied gave us a snapshot of what the evolution of that sexual differentiation pathway could have looked like.” A pupil without the pupal The team found that splicing patterns seen in the louse were similar to the German cockroach. CDCWexler and her colleagues studied three hemimetabolous insect species: the kissing bug (Rhodnius prolixus), the louse (Pediculus humanus) and the German cockroach (Blattella germanica). These insects, like their holometabolous relatives, use a gene regulatory pathway known as transformer (tra)-doublesex (dsx) for sexual determination and differentiation.  “Transformer (tra) and doublesex (dsx) are genes that are present in both males and females,” said Wexler. Tra has two separate versions, called isoforms, which determine the insect’s sex. Dsx, which also has two isoforms, then goes on to influence sexual differentiation, or the development of each sex’s specific physical characteristics. “They have different effects on development depending on the isoforms present and tra controls dsx splicing,” said Wexler. To look at the underlying genetics of sexual determination and differentiation of hemimetabolous insects, the team extracted RNA from each insect species and used a combination of techniques to characterize their tra and dsx splicing patterns. Like their holometabolous relatives, the German cockroaches boasted two isoforms of the dsx gene. But something was missing in their tra-dsx pathway.   “We were expecting that if we saw male and female forms of dsx, we would also see male and female forms of tra, but we failed to detect any different forms of tra that were male-specific or female-specific,” said Wexler. “That was mystery from the paper,” she added. Knockdown genes and sex splicing Wexler and her colleagues made this discovery in the lab by using a technique called RNA interference (RNAi), which allows them to knockdown genes. The functional experiments of the study were performed on the German cockroach.  “We were really puzzled because we could see that just like in holometabolous insects, tra is controlling dsx splicing,” said Wexler. But “we don’t know how it controls dsx splicing because we could not find a female-specific form of tra.” In the lab, Wexler and her colleagues interrupted German cockroach sexual development through the RNAi technique. “We separated them by sex and then we injected males and females with RNAi for either tra or dsx,” said Wexler. “With the females that we injected with RNAi targeting tra, when these females molted into adults, we were like, ‘Oh my god, they look like male cockroaches.’” The team also found that female cockroaches injected with tra produced broods of solely male cockroaches. “We have strong reason to believe that when we interfere with tra, all the females die, so it’s female-specific lethal,” said Wexler.   The splicing patterns seen in the kissing bug were similar to holometabolous insects. Erwin Huebner/University of ManitobaWorking out experimental bugs While no functional experiments were performed in the kissing bug and louse, the team found that splicing patterns seen in the louse were similar to the German cockroach, while the splicing patterns seen in the kissing bug were similar to holometabolous insects. Wexler, who started a postdoctoral position at the Hebrew University of Jerusalem this month, is excited to investigate the origins of this sexual splicing strategy further. “What I really want to do when I start a lab is to try and validate some of the RNAi findings using CRISPR,” said Wexler. But experimenting with CRISPR will prove difficult, as German cockroaches seem to be resistant to the experimental process. “When they’re using CRISPR, most insect biologists take an insect egg and they inject the CRISPR reagents in the egg and then the egg will develop and some of its cells will have mutations,” said Wexler. “German cockroaches don’t lay eggs and walk away from them.” Instead, females carry their eggs in an egg case. “If you remove the case from the female, the eggs die,” said Wexler. “Nobody to my knowledge has done CRISPR in a German cockroach, but I really want to try,” she added.  Stay Informed! Sign up for our monthly email newsletter  "> <a class="addthis_button_facebook"></a> <a class="addthis_button_linkedin"></a> <script> var addthis_share = { templates: { twitter: "Sexual determination and differentiation work in myriad ways across the animal kingdom. In vertebrates, like mammals and fish, sexual determination leads to the development of either ovaries or testis. These organs then secrete hormones that go on to govern the sexual development of the rest of the organism’s body. Insects are a completely different beast. " } } </script> <a class="addthis_button_twitter"></a> <a class="addthis_button_email"></a> <a class="addthis_button_compact"></a> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><aside class="wysiwyg-feature-block u-width--half u-align--right"><h3 class="wysiwyg-feature-block__title">Quick Summary</h3> <div class="wysiwyg-feature-block__body"> <ul><li><strong><em>Unlike sexual development in vertebrates, like mammals and fish, insects use an RNA splicing-based mode of sexual development</em></strong></li> <li><strong><em><span><span><span><span><span><span>In a study appearing in </span></span></span></span></span></span><a href="https://elifesciences.org/articles/47490">eLife</a>, UC Davis researchers <span><span><span><span><span><span>trace this sexual development strategy to hemimetabolous insect </span></span></span></span></span></span></em></strong><span><span><span><span><span><span><strong><em>orders,</em></strong></span></span></span></span></span></span><strong><em><span><span><span><span><span><span> or those that develop from larvae to adults without a pupal stage</span></span></span></span></span></span></em></strong></li> <li><span><span><span><span><span><span><em><strong>The team studied three hemimetabolous insect species: the kissing bug (Rhodnius </strong><strong><em>prolixus</em></strong><strong>), the louse (Pediculus humanus) and the German cockroach (<em>Blattella germanica</em></strong>)</em></span></span></span></span></span></span></li> </ul></div> </aside><p><span><span><span><span><span><span>Sexual determination and differentiation work in myriad ways across the animal kingdom. In vertebrates, like mammals and fish, sexual </span></span></span></span></span></span><span><span><span><span><span><span>determination leads to the development of either ovaries or testis. These organs then secrete hormones that go on to govern the sexual development of the rest of the organism’s body. Insects are a completely different beast.</span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“The way that insects develop male versus female characteristics is using different kinds of RNA splicing and processing,” said Judy Wexler, who graduated from UC Davis in 2018 with a Ph.D. in Population Biology. “The same genes are used to direct male development or female development; it’s just how those genes and RNA are processed that will tell a cell, ‘You’re a male cell, or you’re a female cell.’”</span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span>According to Wexler, insects are the only known animal to perform sexual determination and differentiation via this toggle-like system, which makes use of the biological phenomenon known as “alternative splicing.” Even their closest arthropod relatives, crustaceans, don’t use this sexual development strategy. So it begs the question, how old is the splicing-based mode of sexual differentiation? </span></span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“It really is radically different from the way other animal groups manage their sexual differentiation,” said Professor Artyom Kopp, Department of Evolution and Ecology and director of the Center for Population Biology. “The canonical insect sex pathway is in every developmental biology textbook, but nobody has ever looked at how that pathway came about.”</span></span></span></span></span></span></p> </blockquote> <p><span><span><span><span><span><span>In a study appearing in <em><a href="https://elifesciences.org/articles/47490">eLife</a>, </em>Wexler and her colleagues, including Kopp, trace this splicing-based sexual development strategy to hemimetabolous insect orders, or those that develop from larvae to adults without a pupal stage. These types of insects are more ancient than holometabolous insects, which have a pupal stage.   </span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“The main finding from all of the insects we studied is that together, they represent an intermediate state between what we know to be true in crustaceans and then what we know to be true about sexual development in holometabolous insects,” said Wexler. “These three hemimetabolous insects we studied gave us a snapshot of what the evolution of that sexual differentiation pathway could have looked like.” </span></span></span></span></span></span></p> </blockquote> <h4><span><span><span><strong><span><span><span>A pupil without the pupal </span></span></span></strong></span></span></span></h4> <figure role="group" class="caption caption-img align-right"><img alt="Louse" data-entity-type="file" data-entity-uuid="96956381-df2d-4706-bfc7-1b1e928b44f0" height="328" src="/sites/g/files/dgvnsk2646/files/inline-images/Louse-College-of-Biological-Sciences-UC-Davis.jpg" width="487" /><figcaption>The team found that splicing patterns seen in the louse were similar to the German cockroach. CDC</figcaption></figure><p><span><span><span><span><span><span>Wexler and her colleagues studied three hemimetabolous insect species: the kissing bug (<em>Rhodnius prolixus</em>), the louse (<em>Pediculus humanus</em>) and the German cockroach (<em>Blattella germanica</em>). These insects, like their holometabolous relatives, use a gene regulatory pathway known as <em>transformer</em> (<em>tra</em>)<em>-doublesex </em>(<em>dsx</em>) for sexual determination and differentiation.  </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“<em>Transformer </em>(<em>tra</em>) and <em>doublesex </em>(<em>dsx</em>) are genes that are present in both males and females,” said Wexler. <em>Tra </em>has two separate versions, called isoforms, which determine the insect’s sex. <em>Dsx</em>, which also has two isoforms, then goes on to influence sexual differentiation, or the development of each sex’s specific physical characteristics. “They have different effects on development depending on the isoforms present and <em>tra </em>controls <em>dsx </em>splicing,” said Wexler. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>To look at the underlying genetics of sexual determination and differentiation of hemimetabolous insects, the team extracted RNA from each insect species and used a combination of techniques to characterize their <em>tra</em> and <em>dsx</em> splicing patterns. Like their holometabolous relatives, the German cockroaches boasted two isoforms of the <em>dsx </em>gene. But something was missing in their <em>tra-dsx </em>pathway.<em> </em> </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“We were expecting that if we saw male and female forms of <em>dsx</em>, we would also see male and female forms of <em>tra, </em>but we failed to detect any different forms of <em>tra </em>that were male-specific or female-specific,” said Wexler. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“That was mystery from the paper,” she added. </span></span></span></span></span></span></p> <h4><span><span><span><strong><span><span><span>Knockdown genes and sex splicing</span></span></span></strong></span></span></span></h4> <p><span><span><span><span><span><span>Wexler and her colleagues made this discovery in the lab by using a technique called RNA interference (RNAi), which allows them to knockdown genes. The functional experiments of the study were performed on the German cockroach.  </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“We were really puzzled because we could see that just like in holometabolous insects, <em>tra </em>is controlling <em>dsx </em>splicing,” said Wexler. But “we don’t know how it controls <em>dsx </em>splicing because we could not find a female-specific form of <em>tra.</em>”</span></span></span></span></span></span></p> <p><span><span><span><span><span><span>In the lab, Wexler and her colleagues interrupted German cockroach sexual development through the RNAi technique. </span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“We separated them by sex and then we injected males and females with RNAi for either <em>tra </em>or <em>dsx</em>,” said Wexler. “With the females that we injected with RNAi targeting <em>tra, </em>when these females molted into adults, we were like, ‘Oh my god, they look like male cockroaches.’”</span></span></span></span></span></span></p> </blockquote> <p><span><span><span><span><span><span>The team also found that female cockroaches injected with <em>tra</em> produced broods of solely male cockroaches. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“We have strong reason to believe that when we interfere with <em>tra, </em>all the females die, so it’s female-specific lethal,” said Wexler.  </span></span></span></span></span></span></p> <figure role="group" class="caption caption-img align-left"><img alt="Kissing bug" data-entity-type="file" data-entity-uuid="28256ae9-2dc9-4764-a705-692ba1fe7e3f" height="344" src="/sites/g/files/dgvnsk2646/files/inline-images/Kissing-Bug-College-of-Biological-Sciences-UC-Davis_0.jpg" width="368" /><figcaption>The splicing patterns seen in the kissing bug were similar to holometabolous insects. Erwin Huebner/University of Manitoba</figcaption></figure><h4><span><span><span><strong><span><span><span>Working out experimental bugs</span></span></span></strong></span></span></span></h4> <p><span><span><span><span><span><span>While no functional experiments were performed in the kissing bug and louse, the team found that splicing patterns seen in the louse were similar to the German cockroach, while the splicing patterns seen in the kissing bug were similar to holometabolous insects. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>Wexler, who started a postdoctoral position at the Hebrew University of Jerusalem this month, is excited to investigate the origins of this sexual splicing strategy further.</span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“What I really want to do when I start a lab is to try and validate some of the RNAi findings using CRISPR,” said Wexler. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>But experimenting with CRISPR will prove difficult, as German cockroaches seem to be resistant to the experimental process.</span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“When they’re using CRISPR, most insect biologists take an insect egg and they inject the CRISPR reagents in the egg and then the egg will develop and some of its cells will have mutations,” said Wexler. “German cockroaches don’t lay eggs and walk away from them.” </span></span></span></span></span></span></p> </blockquote> <p><span><span><span><span><span><span>Instead, females carry their eggs in an egg case. “If you remove the case from the female, the eggs die,” said Wexler. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“Nobody to my knowledge has done CRISPR in a German cockroach, but I really want to try,” she added.  </span></span></span></span></span></span></p> <p class="text-align-center"><a class="btn--lg btn--primary" href="https://biology.ucdavis.edu/form/tell-us-more-about-yourself-2">Stay Informed! Sign up for our monthly email newsletter</a><span><span><span><span><span><span> </span></span></span></span></span></span></p> </div> <div class="field field--name-field-sf-article-category field--type-entity-reference field--label-above"> <div class="field__label">Category</div> <div class="field__item"><a href="/articles/ecology-environment" hreflang="en">Ecology and Environment</a></div> </div> <div class="field field--name-field-sf-tags field--type-entity-reference field--label-above"> <div class="field__label">Tags</div> <div class="field__items"> <div class="field__item"><a href="/tags/evolution-and-ecology" hreflang="en">Department of Evolution and Ecology</a></div> <div class="field__item"><a href="/tags/center-population-biology" hreflang="en">Center for Population Biology</a></div> <div class="field__item"><a href="/tags/population-biology" hreflang="en">population biology</a></div> <div class="field__item"><a href="/tags/women-stem" hreflang="en">Women in STEM</a></div> <div class="field__item"><a href="/tags/evolution" hreflang="en">evolution</a></div> <div class="field__item"><a href="/tags/sexual-development" hreflang="en">sexual development</a></div> <div class="field__item"><a href="/tags/insects" hreflang="en">insects</a></div> <div class="field__item"><a href="/tags/population-biology-graduate-group" hreflang="en">Population Biology Graduate Group</a></div> <div class="field__item"><a href="/tags/genetics" hreflang="en">genetics</a></div> <div class="field__item"><a href="/tags/crispr" hreflang="en">CRISPR</a></div> <div class="field__item"><a href="/tags/rna" hreflang="en">RNA</a></div> </div> </div> Wed, 04 Sep 2019 16:36:17 +0000 Greg Watry 3421 at https://biology.ucdavis.edu Mitochondrial Chitter-Chatter: Unveiling the Molecular Structures of Cellular Respiration https://biology.ucdavis.edu/news/mitochondrial-chitter-chatter-unveiling-molecular-structures-cellular-respiration <span class="field field--name-title field--type-string field--label-hidden">Mitochondrial Chitter-Chatter: Unveiling the Molecular Structures of Cellular Respiration </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span lang="" about="/user/5451" typeof="schema:Person" property="schema:name" datatype="">Greg Watry</span> </span> <span class="field field--name-created field--type-created field--label-hidden">September 03, 2019</span> <div class="field field--name-field-sf-primary-image field--type-image field--label-hidden field__item"> <img src="/sites/g/files/dgvnsk2646/files/styles/sf_landscape_16x9/public/images/article/James-Letts-College-of-Biological-Sciences-UC-Davis-3.jpg?h=53a98096&amp;itok=sNnoNknT" width="1280" height="720" alt="James Letts" title="In a Molecular Cell study, Assistant Professor James Letts and colleagues revealed that the function between the complexes in the respiratory supercomplex is more nuanced and variable than previously hypothesized. David Slipher/UC Davis " typeof="foaf:Image" class="image-style-sf-landscape-16x9" /> </div> <div class="addthis_toolbox addthis_default_style addthis_32x32_style" addthis:url="https://biology.ucdavis.edu/articles.rss" addthis:title="Recent News" addthis:description="Quick Summary Dysfunction of the mitochondrial electron transport chain (ETC) is one of the leading causes of metabolic disease The ETC, which comprises four large membrane protein complexes, allows us to generate energy from the food we eat A new study published in Molecular Cell reveals the molecular structure of some of these complexes, uncovering further nuance in the relationship between them In order to generate energy, our bodies transfer electrons from food—sugars, fats and proteins—to molecular oxygen, which allows our cells to respire and function. Performed by the mitochondrial electron transport chain (ETC), this process creates energy-storing and -transporting adenosine triphosphate (ATP), the “molecular currency” for energy in the cell. “It’s a highly interconnected chain of events that basically provides you with this energy source in the end that can be used throughout the cell,” said Assistant Professor James Letts, Department of Molecular and Cellular Biology, of the ETC process leading to ATP. “That’s the main form of energy.” The ETC comprises four large membrane protein complexes, which transfer electrons between one another via electron carrier molecules. In their natural membrane environment, these complexes come together in defined ratios to form what are called “supercomplexes.” Unstable outside of the cell, these supercomplexes and their molecular functionality have long been invisible, but new technologies are providing a glimpse of them.  In a Molecular Cell study, Letts and colleagues revealed that the function between the complexes in the respiratory supercomplex is more nuanced and variable than previously hypothesized. “We are now for the first time able to purify a stable version of the supercomplex that’s functional,” said Letts. “We can now ask, “What is going on?” and ‘Why could it potentially be beneficial for bioenergetic metabolism?’”     Letts and colleagues found unexpectedly that two of the complexes in the respiratory supercomplex actively communicate, relaying information about their molecular structure to each other. The research is unveiling interactions of the ETC at high resolutions, which could provide clues to how ETC dysfunction leads to disease. “Dysfunction of the mitochondrial ETC is one of the leading causes of metabolic disease and largely the prognosis is poor,” said Letts. “In general, 50% of patients with ETC deficiencies die within the first two years of life and only 25% reach 10 years old. Despite this large medical need, currently there are no effective treatments.” A high-pressure cell homogenizer helps Letts bring cellular samples to a state where all properties of the sample are equal in composition. David Slipher/UC DavisProtein complex, let my molecules go! In the study, Letts and colleagues isolated the supercomplex made up of two of the four ETC complexes, known as complex I and complex III, from the cells of sheep hearts. The heart’s constant pumping requires a lot of energy, meaning its muscle tissue is brimming with mitochondria. The red color of the heart is actually due to the high amount of mitochondria. A previous hypothesis suggested that, when bound together in the supercomplex,  complex I and complex III shuttle ubiquinone molecules—essential to energy transfer—back and forth in a trapped manner. “If they trap ubiquinone between complex I and complex III and prevent it from exchanging with the broader ubiquinone pool in the membrane it might allow for quicker electron transfer overall,” said Letts, explaining the previous hypothesis. “There are other enzyme systems where this is the case.”      When the team trapped ubiquinone between the complexes in their assays, however, they found the overall rate of the system declined. “Complex III becomes rate limiting and therefore complex I can’t turn over as fast as it could if ubiquinone was free to exchange with the broader pool,” said Letts. When the team freed the ubiquinone, the supercomplex performed much faster, showing that trapping ubiquinone decreases the rate of electron transfer and disproving the previous hypothesis. A technique called single-particle cryo-electron microscopy gave the team an unprecedented look at the structure of complex I and complex III together. This allowed them to create 3-D reconstructions of the molecular structures.   “One thing we’re able to do with electron microscopy maps is we’re able to look at what’s called local resolution and that’s a measure of the flexibility of different regions of the complexes,” said Letts.       A technique called single-particle cryo-electron microscopy gave Letts and his team an unprecedented look at the structure of complex I and complex III together. David Slipher/UC Davis Unexpected crosstalk between regions  The team also found that complex I exhibited “open” and “closed” conformations and that these conformations affected the functionality and conformation of complex III.  Based on the experiments, the team solved four different structures of the respiratory supercomplex. One of the standout findings was that complex I can affect the symmetry of complex III, which is a dimer, meaning it’s made from two identical proteins. Complex III has four ubiquinone binding sites. The researchers found that when complex III was attached to complex I, the ubiquinone binding site on complex III closest to complex I, unlike the other three sites, did not have ubiquinone bound. “There seems to be functionally relevant symmetry breaking of complex III,” said Letts.      The findings indicate that there’s crosstalk between complex I and complex III. Letts said the asymmetric ubiquinone binding site could be interacting with complex I somehow. “Complex III is talking to complex I essentially and complex I is talking to complex III and they’re telling each other about what catalytic states they’re in,” he said. “We don’t exactly understand how that communication is going on but complex III clearly can sense the state of complex I based on this data.” “It’s really remarkable,” he added. “Nobody had predicted such a nuanced role for these supercomplexes. It makes us have to rethink everything we thought we knew about how they work and why they evolved.”   The team also found that complex I exhibited “open” and “closed” conformations and that these conformations affected the functionality and conformation of complex III. David Slipher/UC Davis Detergents? Who needs ‘em? One of the difficult things about working with membrane proteins, like complex I and complex III, is they’re hydrophobic, or repelled by water. They prefer oily membrane-like environments, like their home inside the cell. Outside of the cell membrane, they clump together and are useless. To work with membrane proteins in the lab, molecular biologists usually use detergents, which work similarly to laundry detergents. In the lab, Letts runs tests to identify the molecular composition of the green fluorescent protein he uses in his experiments. David Slipher/UC Davis “They’re obviously a little more sophisticated, but it’s basically the same thing,” said Letts. “They go into the membrane and they stabilize the hydrophobic parts of the membrane protein and allow it to come into solution so that you can work with it in solution.” While advantageous, these detergents can also get in the way of science, sometimes making it difficult to perform activity assays r glean molecular structures. Letts bypassed these molecular hiccups in the Molecular Cell study by using amphipols, a polymer that can wrap around membrane proteins and stabilize them in a solution.   “You can remove all the detergent that normally you need around to keep it soluble,” said Letts. “That’s what we were able to do with this supercomplex.” “This is the first time anyone has ever been able to purify it,” he added. The research was supported by the European Research Council through the Marie Skłodowska Curie Individual Fellowship. Stay Informed! Sign up for our monthly email newsletter  Letts&#039; research is unveiling interactions of the ETC at high resolutions, which could provide clues to how ETC dysfunction leads to disease. David Slipher/UC Davis  "> <a class="addthis_button_facebook"></a> <a class="addthis_button_linkedin"></a> <script> var addthis_share = { templates: { twitter: "In order to generate energy, our bodies transfer electrons from food—sugars, fats and proteins—to molecular oxygen, which allows our cells to respire and function. Performed by the mitochondrial electron transport chain (ETC), this process creates ATP, the “molecular currency” for energy in the cell. In a Molecular Cell study, Assistant Professor James Letts, Department of Molecular and Cellular Biology, and colleagues reveal further nuances of the ETC. " } } </script> <a class="addthis_button_twitter"></a> <a class="addthis_button_email"></a> <a class="addthis_button_compact"></a> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><aside class="wysiwyg-feature-block u-width--half u-align--right"><h3 class="wysiwyg-feature-block__title">Quick Summary</h3> <div class="wysiwyg-feature-block__body"> <ul><li><em><strong>Dysfunction of the mitochondrial electron transport chain (ETC) is one of the leading causes of metabolic disease</strong></em></li> <li><em><em><strong>The ETC, which comprises four large membrane protein complexes, allows us to generate energy from the food we eat</strong></em></em></li> <li><strong><em>A new study published in Molecular Cell reveals the molecular structure of some of these complexes, uncovering further nuance in the relationship between them</em></strong></li> </ul></div> </aside><p><span><span><span><span><span><span>In order to generate energy, our bodies transfer electrons from food—sugars, fats and proteins—to molecular oxygen, which allows our cells </span></span></span></span></span></span><span><span><span><span><span><span>to respire and function. Performed by the mitochondrial electron transport chain (ETC), this process creates energy-storing and -transporting adenosine triphosphate (ATP), the “molecular currency” for energy in the cell.</span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“It’s a highly interconnected chain of events that basically provides you with this energy source in the end that can be used throughout the cell,” said Assistant Professor James Letts, Department of Molecular and Cellular Biology, of the ETC process leading to ATP. “That’s the main form of energy.” </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>The ETC comprises four large membrane protein complexes, which transfer electrons between one another via electron carrier molecules. In their natural membrane environment, these complexes come together in defined ratios to form what are called “supercomplexes.” Unstable outside of the cell, these supercomplexes and their molecular functionality have long been invisible, but new technologies are providing a glimpse of them.  </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>In a <em><a href="https://www.cell.com/molecular-cell/fulltext/S1097-2765(19)30552-0">Molecular Cell</a> </em>study, Letts and colleagues revealed that the function between the complexes in the respiratory supercomplex is more nuanced and variable than previously hypothesized. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“We are now for the first time able to purify a stable version of the supercomplex that’s functional,” said Letts. “We can now ask, “What is going on?” and ‘Why could it potentially be beneficial for bioenergetic metabolism?’”    </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>Letts and colleagues found unexpectedly that two of the complexes in the respiratory supercomplex actively communicate, relaying information about their molecular structure to each other. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>The research is unveiling interactions of the ETC at high resolutions, which could provide clues to how ETC dysfunction leads to disease. </span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“Dysfunction of the mitochondrial ETC is one of the leading causes of metabolic disease and largely the prognosis is poor,” said Letts. “In general, 50% of patients with ETC deficiencies die within the first two years of life and only 25% reach 10 years old. Despite this large medical need, currently there are no effective treatments.”</span></span></span></span></span></span></p> </blockquote> <figure role="group" class="caption caption-img"><img alt="Cell homogenizer" data-entity-type="file" data-entity-uuid="cb6e0077-9f6b-421d-a19b-2fdd43e620c9" src="/sites/g/files/dgvnsk2646/files/inline-images/James-Letts-College-of-Biological-Sciences-UC-Davis-2.jpg" /><figcaption>A high-pressure cell homogenizer helps Letts bring cellular samples to a state where all properties of the sample are equal in composition. David Slipher/UC Davis</figcaption></figure><h4><span><span><span><strong><span><span><span>Protein complex, let my molecules go!</span></span></span></strong></span></span></span></h4> <p><span><span><span><span><span><span>In the study, Letts and colleagues isolated the supercomplex made up of two of the four ETC complexes, known as complex I and complex III, from the cells of sheep hearts. The heart’s constant pumping requires a lot of energy, meaning its muscle tissue is brimming with mitochondria. The red color of the heart is actually due to the high amount of mitochondria. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>A previous hypothesis suggested that, when bound together in the supercomplex,  complex I and complex III shuttle ubiquinone molecules—essential to energy transfer—back and forth in a trapped manner. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“If they trap ubiquinone between complex I and complex III and prevent it from exchanging with the broader ubiquinone pool in the membrane it might allow for quicker electron transfer overall,” said Letts, explaining the previous hypothesis. “There are other enzyme systems where this is the case.”     </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>When the team trapped ubiquinone between the complexes in their assays, however, they found the overall rate of the system declined. “Complex III becomes rate limiting and therefore complex I can’t turn over as fast as it could if ubiquinone was free to exchange with the broader pool,” said Letts. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>When the team freed the ubiquinone, the supercomplex performed much faster, showing that trapping ubiquinone decreases the rate of electron transfer and disproving the previous hypothesis.</span></span></span></span></span></span></p> <p><span><span><span><span><span><span>A technique called single-particle cryo-electron microscopy gave the team an unprecedented look at the structure of complex I and complex III together. This allowed them to create 3-D reconstructions of the molecular structures.  </span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“One thing we’re able to do with electron microscopy maps is we’re able to look at what’s called local resolution and that’s a measure of the flexibility of different regions of the complexes,” said Letts.      </span></span></span></span></span></span></p> </blockquote> <figure role="group" class="caption caption-img"><img alt="James Letts at the computer" data-entity-type="file" data-entity-uuid="0bd0a28b-5d90-4f62-81d3-3a8c25814ffa" src="/sites/g/files/dgvnsk2646/files/inline-images/James-Letts-College-of-Biological-Sciences-UC-Davis-5.jpg" /><figcaption>A technique called single-particle cryo-electron microscopy gave Letts and his team an unprecedented look at the structure of complex I and complex III together. David Slipher/UC Davis </figcaption></figure><h4><span><span><span><strong><span><span><span>Unexpected crosstalk between regions </span></span></span></strong></span></span></span></h4> <p><span><span><span><span><span><span> The team also found that complex I exhibited “open” and “closed” conformations and that these conformations affected the functionality and conformation of complex III.  Based on the experiments, the team solved four different structures of the respiratory supercomplex. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>One of the standout findings was that complex I can affect the symmetry of complex III, which is a dimer, meaning it’s made from two identical proteins. Complex III has four ubiquinone binding sites. The researchers found that when complex III was attached to complex I, the ubiquinone binding site on complex III closest to complex I, unlike the other three sites, did not have ubiquinone bound. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“There seems to be functionally relevant symmetry breaking of complex III,” said Letts.     </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>The findings indicate that there’s crosstalk between complex I and complex III. Letts said the asymmetric ubiquinone binding site could be interacting with complex I somehow.</span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“Complex III is talking to complex I essentially and complex I is talking to complex III and they’re telling each other about what catalytic states they’re in,” he said. “We don’t exactly understand how that communication is going on but complex III clearly can sense the state of complex I based on this data.” </span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“It’s really remarkable,” he added. “Nobody had predicted such a nuanced role for these supercomplexes. It makes us have to rethink everything we thought we knew about how they work and why they evolved.” </span></span></span></span></span></span></p> </blockquote> <figure role="group" class="caption caption-img"><img alt="Lab machine" data-entity-type="file" data-entity-uuid="50d74186-65ab-4f64-95da-bce898a9b9c6" src="/sites/g/files/dgvnsk2646/files/inline-images/James-Letts-College-of-Biological-Sciences-UC-Davis-6_0.jpg" /><figcaption> The team also found that complex I exhibited “open” and “closed” conformations and that these conformations affected the functionality and conformation of complex III. David Slipher/UC Davis </figcaption></figure><h4><span><span><span><strong><span><span><span>Detergents? Who needs ‘em? </span></span></span></strong></span></span></span></h4> <p><span><span><span><span><span><span>One of the difficult things about working with membrane proteins, like complex I and complex III, is they’re hydrophobic, or repelled by water. They prefer oily membrane-like environments, like their home inside the cell. Outside of the cell membrane, they clump together and are useless. To work with membrane proteins in the lab, molecular biologists usually use detergents, which work similarly to laundry detergents.</span></span></span></span></span></span></p> <figure role="group" class="caption caption-img align-right"><img alt="Green fluorescent protein" data-entity-type="file" data-entity-uuid="5729ad87-ffda-4d7b-bd93-689f3c620377" height="367" src="/sites/g/files/dgvnsk2646/files/inline-images/James-Letts-College-of-Biological-Sciences-UC-Davis-7.jpg" width="367" /><figcaption>In the lab, Letts runs tests to identify the molecular composition of the green fluorescent protein he uses in his experiments. David Slipher/UC Davis</figcaption></figure><blockquote> <p><span><span><span><span><span><span>“They’re obviously a little more sophisticated, but it’s basically the same thing,” said Letts. “They go into the membrane and they stabilize the hydrophobic parts of the membrane protein and allow it to come into solution so that you can work with it in solution.” </span></span></span></span></span></span></p> </blockquote> <p><span><span><span><span><span><span>While advantageous, these detergents can also get in the way of science, sometimes making it difficult to perform activity assays r glean molecular structures. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>Letts bypassed these molecular hiccups in the <em>Molecular Cell </em>study by using amphipols, a polymer that can wrap around membrane proteins and stabilize them in a solution.   </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“You can remove all the detergent that normally you need around to keep it soluble,” said Letts. “That’s what we were able to do with this supercomplex.” </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“This is the first time anyone has ever been able to purify it,” he added. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>The research was supported by the European Research Council through the Marie Skłodowska Curie Individual Fellowship. </span></span></span></span></span></span></p> <p class="text-align-center"><a class="btn--lg btn--primary" href="https://biology.ucdavis.edu/form/tell-us-more-about-yourself-2">Stay Informed! Sign up for our monthly email newsletter</a><span><span><span><span><span><span> </span></span></span></span></span></span></p> <figure role="group" class="caption caption-img"><img alt="James Letts" data-entity-type="file" data-entity-uuid="bd819658-b4ec-4514-adb2-b5b28a6c9a1c" src="/sites/g/files/dgvnsk2646/files/inline-images/James-Letts-College-of-Biological-Sciences-UC-Davis.jpg" /><figcaption>Letts' research is unveiling interactions of the ETC at high resolutions, which could provide clues to how ETC dysfunction leads to disease. David Slipher/UC Davis</figcaption></figure><p> </p> </div> <div class="field field--name-field-sf-article-category field--type-entity-reference field--label-above"> <div class="field__label">Category</div> <div class="field__item"><a href="/articles/genetics-microbiology" hreflang="en">Cellular and Microbiology</a></div> </div> <div class="field field--name-field-sf-tags field--type-entity-reference field--label-above"> <div class="field__label">Tags</div> <div class="field__items"> <div class="field__item"><a href="/tags/molecular-and-cellular-biology" hreflang="en">Department of Molecular and Cellular Biology</a></div> <div class="field__item"><a href="/tags/biophysics-graduate-group" hreflang="en">Biophysics Graduate Group</a></div> <div class="field__item"><a href="/tags/biochemistry-molecular-cellular-and-developmental-biology-graduate-group" hreflang="en">Biochemistry, Molecular, Cellular and Developmental Biology Graduate Group</a></div> <div class="field__item"><a href="/tags/electron-transport-chain" hreflang="en">electron transport chain</a></div> <div class="field__item"><a href="/tags/proteins" hreflang="en">proteins</a></div> <div class="field__item"><a href="/tags/mitochondria" hreflang="en">mitochondria</a></div> <div class="field__item"><a href="/tags/human-health" hreflang="en">human health</a></div> <div class="field__item"><a href="/tags/human-disease" hreflang="en">human disease</a></div> </div> </div> Tue, 03 Sep 2019 15:37:21 +0000 Greg Watry 3401 at https://biology.ucdavis.edu Gatekeeper of the Cellular Highway: Study Reveals Novel Behaviors of the Alzheimer’s Disease Protein Tau https://biology.ucdavis.edu/news/gatekeeper-cellular-highway-study-reveals-novel-behaviors-alzheimers-disease-protein-tau <span class="field field--name-title field--type-string field--label-hidden">Gatekeeper of the Cellular Highway: Study Reveals Novel Behaviors of the Alzheimer’s Disease Protein Tau</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span lang="" about="/user/5451" typeof="schema:Person" property="schema:name" datatype="">Greg Watry</span> </span> <span class="field field--name-created field--type-created field--label-hidden">September 02, 2019</span> <div class="field field--name-field-sf-primary-image field--type-image field--label-hidden field__item"> <img src="/sites/g/files/dgvnsk2646/files/styles/sf_landscape_16x9/public/images/article/Tau-Tangles-College-of-Biological-Sciences-UC-Davis_Page_1.jpg?h=d6378a9e&amp;itok=LBlU6W4T" width="1280" height="720" alt="Microtubule" title="In a new study appearing in Nature Cell Biology, UC Davis researchers found that tau molecules can congregate together in a novel, reversible way, which appears to be distinct from the irreversible tangle formation observed in neurodegenerative disease. N Molecular Systems, Inc." typeof="foaf:Image" class="image-style-sf-landscape-16x9" /> </div> <div class="addthis_toolbox addthis_default_style addthis_32x32_style" addthis:url="https://biology.ucdavis.edu/articles.rss" addthis:title="Recent News" addthis:description="Quick Summary Neurofibrillary tangles called &quot;tau tangles&quot; are characteristic of those with Alzheimer&#039;s disease or traumatic brain injury The natural physiological function of tau in healthy brains remains a mystery In a new study, UC Davis researchers found tau molecules congregate together in a reversible way that appears to be distinct from the tau tangles seen in  neurodegenerative diseases In the brains of those with Alzheimer’s disease, traumatic brain injury and other neurodegenerative disorders, insoluble fibers composed of a protein called tau build up inside of neurons, eventually creating a tangled mess characteristic of these diseases. “These tangles grow and grow and grow inside of the cells and at some point that gums up the works so much that the cell just dies,” said Assistant Professor Richard McKenney, Department of Molecular and Cellular Biology. “But (after death) the protein plaques are left behind and can possibly spread to other cells in the brain.” Tau tangles (or ‘neurofibrillary tangles’) have become a litmus test for Alzheimer’s disease. But are they the cause of it or the result? The physiological function of tau inside of neurons remains a mystery, hampering an understanding of what tau normally does, and what goes wrong when tau tangles form inside of neurons.   In a new study appearing in Nature Cell Biology, McKenney, Assistant Professor Kassandra Ori-McKenney and their colleagues found that tau molecules can congregate together in a novel,  reversible way, which appears to be distinct from the irreversible tangle formation observed in neurodegenerative diseases. Once they come together, groups of tau molecules act like gatekeepers along the cell’s microtubules, the highways of the cell’s molecular transport system. “Using a technique that allows us to visualize the behavior of single tau molecules, we directly observed that tau can self-associate even in the absence of a disease state,” said McKenney. “We’re proposing that self-association of tau molecules is actually a normal thing that can somehow go wrong and cause these neurodegenerative diseases.” The new research upends the dogma that tau typically exists as a single molecule along the cell’s highways and that tau self-association is only present in diseased brain cells. “There must be a physiological function for this protein, even though most studies focus on it in the diseased state,” said Ori-McKenney. “The problem with that is if you only focus on the disease states there’s only so far you can go. In order to really understand how it goes awry, you need to understand its normal function.”  In the experiments, the tau molecules congregated together in specific regions along the microtubules, which McKenney and Ori-McKenney refer to as “condensates.”  David Slipher/UC DavisA molecular traffic light Tau belongs to a large group of proteins called microtubule-associated proteins (MAPs), which bind to intracellular microtubules and can affect the transport functions of the motor proteins dynein and kinesin. Using a technique called single-molecule microscopy, Ori-McKenney, McKenney and their team directly observed interactions between purified tau molecules and purified microtubules outside of the cell environment. “We immediately saw that they were behaving differently than other types of MAPs that we had looked at in the lab,” said McKenney. In the experiments, the tau molecules congregated together in specific regions along the microtubules, which McKenney and Ori-McKenney refer to as “condensates.” Compartmentalizing the microtubule, these condensates, according to the researchers, were formed through the dynamic self-association of tau molecules. The researchers believe this novel behavior of tau was driven by a process known as phase separation. “The most simple way to think about this is oil and water,” said McKenney. “When you mix oil and water, the oil separates itself out from the water. This is due to the self-association of the oil molecules with each other, akin to the self-association of tau molecules that we observe in our experiments.” To uncover the function of these tau condensates, the team tested their effects on molecular motor proteins and another protein called spastin, a severing enzyme that cuts and remodels microtubules within cells. The researchers found that the condensates acted like a selective molecular sieve, allowing some motor proteins, but not others, to pass through, fully protecting the microtubule from spastin’s severing activity.  “By forming a selectively permeable sheath around the microtubule, the condensate is saying to these other molecules, ‘Okay, you can act there and there, but you can’t act here,’” said McKenney. The condensates, the researchers found, acted like directional traffic lights for the motor proteins dynein and kinesin. “I think that tau is a really excellent candidate for being one of the major traffic lights within the axon of the neuron in terms of its direction of motor transport and the other enzymes that act on the microtubule,” said Ori-McKenney. Protein talk on the patio Discovers like this drive the curiosity and after-hours discussions between Ori-McKenney and McKenney. Now that they understand tau naturally forms these condensates, Ori-McKenney and McKenney have many new questions. What leads to the unwieldy tau tangles present in neurodegenerative diseases? Are they a byproduct of some kind of dysfunction of tau’s condensation? An intriguing possibility since self-association of tau molecules underlies both processes.   “This paper, like much of our work, just kind of sprung out of our collective interest in the biology of the cell’s cytoskeleton,” said Ori-McKenney. “We sit on our patio at night and discuss what are the most interesting directions we can take in order to understand this protein and others in more depth.” The researchers hope to partner with the UC Davis Alzheimer’s Disease Center in an effort to obtain patient brain samples and expand their research on tau behavior to include tau in a genuinely pathological-state. The research was carried out by Biochemistry, Molecular, Cellular and Developmental Biology graduate students Ruensern Tan, with help from Tracy Tan, and also undergraduate Aileen Lam, who is the recipient of the 2019 Hanson Family Undergraduate Research Publication Award. The research was funded by grants from the National Institutes of Health and the Pew Foundation.    Stay Informed! Sign up for our monthly email newsletter  “This paper, like much of our work, just kind of sprung out of our collective interest in the biology of the cell’s cytoskeleton,” said Ori-McKenney. “We sit on our patio at night and discuss what are the most interesting directions we can take in order to understand this protein and others in more depth.”  David Slipher/UC Davis  "> <a class="addthis_button_facebook"></a> <a class="addthis_button_linkedin"></a> <script> var addthis_share = { templates: { twitter: "In a new study appearing in Nature Cell Biology, UC Davis researchers found that tau molecules can congregate together in a novel, reversible way, which appears to be distinct from the irreversible tangle formation observed in neurodegenerative disease. " } } </script> <a class="addthis_button_twitter"></a> <a class="addthis_button_email"></a> <a class="addthis_button_compact"></a> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><aside class="wysiwyg-feature-block u-width--half u-align--right"><h3 class="wysiwyg-feature-block__title">Quick Summary</h3> <div class="wysiwyg-feature-block__body"> <ul><li><em><strong>Neurofibrillary tangles called "tau tangles" are characteristic of those with Alzheimer's disease or traumatic brain injury</strong></em></li> <li><em><strong>The natural physiological function of tau in healthy brains remains a mystery</strong></em></li> <li><strong><em>In a new study, UC Davis researchers found tau molecules congregate together in a reversible way that appears to be distinct from the tau tangles seen in  neurodegenerative diseases</em></strong></li> </ul></div> </aside><p><span><span><span><span><span><span>In the brains of those with Alzheimer’s disease, traumatic brain injury and other neurodegenerative disorders, </span></span></span></span></span></span><span><span><span><span><span><span>insoluble fibers composed of a protein called tau build up inside of neurons, eventually creating a tangled mess characteristic of these diseases. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“These tangles grow and grow and grow inside of the cells and at some point that gums up the works so much that the cell just dies,” said Assistant Professor Richard McKenney, Department of Molecular and Cellular Biology. “But (after death) the protein plaques are left behind and can possibly spread to other cells in the brain.” </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>Tau tangles (or ‘neurofibrillary tangles’) have become a litmus test for Alzheimer’s disease. But are they the cause of it or the result? The physiological function of tau inside of neurons remains a mystery, hampering an understanding of what tau normally does, and what goes wrong when tau tangles form inside of neurons.  </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>In a new study appearing in <em><a href="https://www.nature.com/articles/s41556-019-0375-5">Nature Cell Biology</a>, </em>McKenney, Assistant Professor Kassandra Ori-McKenney and their colleagues found that tau molecules can congregate together in a novel,  reversible way, which appears to be distinct from the irreversible tangle formation observed in neurodegenerative diseases. Once they come together, groups of tau molecules act like gatekeepers along the cell’s microtubules, the highways of the cell’s molecular transport system.<em> </em></span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“Using a technique that allows us to visualize the behavior of single tau molecules, we directly observed that tau can self-associate even in the absence of a disease state,” said McKenney. “We’re proposing that self-association of tau molecules is actually a normal thing that can somehow go wrong and cause these neurodegenerative diseases.” </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>The new research upends the dogma that tau typically exists as a single molecule along the cell’s highways and that tau self-association is only present in diseased brain cells. </span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“There must be a physiological function for this protein, even though most studies focus on it in the diseased state,” said Ori-McKenney. “The problem with that is if you only focus on the disease states there’s only so far you can go. In order to really understand how it goes awry, you need to understand its normal function.” </span></span></span></span></span></span></p> </blockquote> <figure role="group" class="caption caption-img"><img alt="Richard McKenney and Kassandra Ori-McKenney" data-entity-type="file" data-entity-uuid="a321ed73-2b90-456a-9de3-d4c0ec53512c" src="/sites/g/files/dgvnsk2646/files/inline-images/UC-Davis-College-of-Biological-Sciences-McKenney-Ori-McKenney-Lab_%283_of_5%29_0_0.jpg" /><figcaption>In the experiments, the tau molecules congregated together in specific regions along the microtubules, which McKenney and Ori-McKenney refer to as “condensates.”  David Slipher/UC Davis</figcaption></figure><h4><span><span><span><strong><span><span><span>A molecular traffic light</span></span></span></strong></span></span></span></h4> <p><span><span><span><span><span><span>Tau belongs to a large group of proteins called microtubule-associated proteins (MAPs), which bind to intracellular microtubules and can affect the transport functions of the motor proteins dynein and kinesin. Using a technique called single-molecule microscopy, Ori-McKenney, McKenney and their team directly observed interactions between purified tau molecules and purified microtubules outside of the cell environment. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“We immediately saw that they were behaving differently than other types of MAPs that we had looked at in the lab,” said McKenney. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>In the experiments, the tau molecules congregated together in specific regions along the microtubules, which McKenney and Ori-McKenney refer to as “condensates.” Compartmentalizing the microtubule, these condensates, according to the researchers, were formed through the dynamic self-association of tau molecules. The researchers believe this novel behavior of tau was driven by a process known as phase separation. </span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“The most simple way to think about this is oil and water,” said McKenney. “When you mix oil and water, the oil separates itself out from the water. This is due to the self-association of the oil molecules with each other, akin to the self-association of tau molecules that we observe in our experiments.”</span></span></span></span></span></span></p> </blockquote> <p><span><span><span><span><span><span>To uncover the function of these tau condensates, the team tested their effects on molecular motor proteins and another protein called spastin, a severing enzyme that cuts and remodels microtubules within cells. The researchers found that the condensates acted like a selective molecular sieve, allowing some motor proteins, but not others, to pass through, fully protecting the microtubule from spastin’s severing activity.  </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“By forming a selectively permeable sheath around the microtubule, the condensate is saying to these other molecules, ‘Okay, you can act there and there, but you can’t act here,’” said McKenney. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>The condensates, the researchers found, acted like directional traffic lights for the motor proteins dynein and kinesin. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“I think that tau is a really excellent candidate for being one of the major traffic lights within the axon of the neuron in terms of its direction of motor transport and the other enzymes that act on the microtubule,” said Ori-McKenney. </span></span></span></span></span></span></p> <h4><span><span><span><strong><span><span><span>Protein talk on the patio</span></span></span></strong></span></span></span></h4> <p><span><span><span><span><span><span>Discovers like this drive the curiosity and after-hours discussions between Ori-McKenney and McKenney. Now that they understand tau naturally forms these condensates, Ori-McKenney and McKenney have many new questions. What leads to the unwieldy tau tangles present in neurodegenerative diseases? Are they a byproduct of some kind of dysfunction of tau’s condensation? An intriguing possibility since self-association of tau molecules underlies both processes.  </span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“This paper, like much of our work, just kind of sprung out of our collective interest in the biology of the cell’s cytoskeleton,” said Ori-McKenney. “We sit on our patio at night and discuss what are the most interesting directions we can take in order to understand this protein and others in more depth.” </span></span></span></span></span></span></p> </blockquote> <p><span><span><span><span><span><span>The researchers hope to partner with the UC Davis Alzheimer’s Disease Center in an effort to obtain patient brain samples and expand their research on tau behavior to include tau in a genuinely pathological-state. The research was carried out by Biochemistry, Molecular, Cellular and Developmental Biology graduate students Ruensern Tan, with help from Tracy Tan, and also undergraduate Aileen Lam, who is the recipient of the 2019 Hanson Family Undergraduate Research Publication Award. The research was funded by grants from the National Institutes of Health and the Pew Foundation.   </span></span></span></span></span></span></p> <p class="text-align-center"><a class="btn--lg btn--primary" href="https://biology.ucdavis.edu/form/tell-us-more-about-yourself-2">Stay Informed! Sign up for our monthly email newsletter</a><span><span><span><span><span><span> </span></span></span></span></span></span></p> <figure role="group" class="caption caption-img"><img alt="Kassandra Ori-McKenney and Richard McKenney" data-entity-type="file" data-entity-uuid="be071d25-1017-40a2-8a35-9e805f8a2b29" src="/sites/g/files/dgvnsk2646/files/inline-images/UC-Davis-College-of-Biological-Sciences-McKenney-Ori-McKenney-Lab_%282_of_5%29.jpg" /><figcaption>“This paper, like much of our work, just kind of sprung out of our collective interest in the biology of the cell’s cytoskeleton,” said Ori-McKenney. “We sit on our patio at night and discuss what are the most interesting directions we can take in order to understand this protein and others in more depth.”  David Slipher/UC Davis</figcaption></figure><p> </p> </div> <div class="field field--name-field-sf-article-category field--type-entity-reference field--label-above"> <div class="field__label">Category</div> <div class="field__item"><a href="/articles/genetics-microbiology" hreflang="en">Cellular and Microbiology</a></div> </div> <div class="field field--name-field-sf-tags field--type-entity-reference field--label-above"> <div class="field__label">Tags</div> <div class="field__items"> <div class="field__item"><a href="/tags/molecular-and-cellular-biology" hreflang="en">Department of Molecular and Cellular Biology</a></div> <div class="field__item"><a href="/tags/neurobiology" hreflang="en">neurobiology</a></div> <div class="field__item"><a href="/tags/neuroscience" hreflang="en">neuroscience</a></div> <div class="field__item"><a href="/tags/motor-proteins" hreflang="en">motor proteins</a></div> <div class="field__item"><a href="/tags/proteins" hreflang="en">proteins</a></div> <div class="field__item"><a href="/tags/tau" hreflang="en">tau</a></div> <div class="field__item"><a href="/tags/human-disease" hreflang="en">human disease</a></div> <div class="field__item"><a href="/tags/alzheimers-disease" hreflang="en">Alzheimer&#039;s disease</a></div> <div class="field__item"><a href="/tags/traumatic-brain-injury" hreflang="en">traumatic brain injury</a></div> <div class="field__item"><a href="/tags/microtubules" hreflang="en">microtubules</a></div> <div class="field__item"><a href="/tags/undergraduate-student-news" hreflang="en">Undergraduate Student News</a></div> <div class="field__item"><a href="/tags/graduate-student-news" hreflang="en">Graduate Student News</a></div> <div class="field__item"><a href="/tags/biochemistry-molecular-cellular-and-developmental-biology-graduate-group" hreflang="en">Biochemistry, Molecular, Cellular and Developmental Biology Graduate Group</a></div> </div> </div> Mon, 02 Sep 2019 17:23:00 +0000 Greg Watry 3396 at https://biology.ucdavis.edu High-Definition Biology: NSF Funds Development of Next Generation Computational Tools for Single-Cell Analysis https://biology.ucdavis.edu/news/high-definition-biology-Quon <span class="field field--name-title field--type-string field--label-hidden">High-Definition Biology: NSF Funds Development of Next Generation Computational Tools for Single-Cell Analysis</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span lang="" about="/user/5451" typeof="schema:Person" property="schema:name" datatype="">Greg Watry</span> </span> <span class="field field--name-created field--type-created field--label-hidden">August 28, 2019</span> <div class="field field--name-field-sf-primary-image field--type-image field--label-hidden field__item"> <img src="/sites/g/files/dgvnsk2646/files/styles/sf_landscape_16x9/public/images/article/Gerald-Quon-College-of-Biological-Sciences-UC-Davis-3.jpg?h=06ac0d8c&amp;itok=O3KEokoc" width="1280" height="720" alt="Gerald Quon" title="Thanks to a roughly 5-year, $850,000 CAREER grant from the National Science Foundation, Assistant Professor Gerald Quon will develop next-generation computational tools that will allow researchers to better understand and analyze single-cell genomic data. David Slipher/UC Davis" typeof="foaf:Image" class="image-style-sf-landscape-16x9" /> </div> <div class="addthis_toolbox addthis_default_style addthis_32x32_style" addthis:url="https://biology.ucdavis.edu/articles.rss" addthis:title="Recent News" addthis:description="Quick Summary A 5-year, $850,000 CAREER grant from the NSF will help Gerald Quon develop next-generation computational tools to analyze single-cell genomic data With the grant, Quon also hopes to develop quantitative biology programs for high school, undergraduate and graduate students Students interested in assisting Quon should email him at gquon@ucdavis.edu  The human body is complex, comprising trillions of cells that work in tandem to promote proper physiological function. But our systems can go awry, leading to the development of a whole host of diseases, like cancer and Alzheimer’s. The keys to unlocking potential therapeutics for these devastating diseases lie in the genome, the proverbial “blueprint for life.” With each passing day, biotechnologies advance, allowing scientists to dissect these diseases at high-definition, single-cell resolutions. “Previous technologies relied on collecting DNA or RNA from up to millions of cells to make a single measurement,” said Assistant Professor Gerald Quon, Department of Molecular and Cellular Biology. “But if you have to combine all the material you get from millions of cells, you lose a lot of resolution compared to if you could look at each cell individually.” “Genomics technologies today are moving towards single-cell resolution,” he added, “and there’s a lot of new challenges associated with data analysis of single-cell genomic data.” One of those challenges is the innumerable data generated from genomic sequencing. It’s gargantuan, more than humans can understand alone. To accomplish this, we need help from new computational tools and cutting-edge hardware to power machine learning.    To make sense of data generated from genomic sequencing, we need help from cutting-edge hardware to power machine learning. David Sliper/UC Davis   Thanks to a roughly 5-year, $850,000 CAREER grant from the National Science Foundation, Quon, who also holds an appointment at the UC Davis Genome Center, will develop next-generation computational tools that will allow researchers to better understand and analyze single-cell genomic data. New cells on the block One of Quon’s main goals is to develop computational tools that’ll allow researchers to better understand how cell-to-cell communication affects molecular function and tissue development. “We want to provide a much higher resolution snapshot of what’s happening in tissues,” said Quon. “For example, in the brain, there’s a lot of variation even between neighboring cells.”    Tissues are much more than just collections of cells individually working on their own. They often communicate with each other in order to coordinate function and development, and so it is important to understand how each cell’s environment impacts its inner workings. “This is just the beginning,” said Quon. “In the next few years, people are going to release technologies where you actually measure in 2-D and 3-D space where each cell came from. So now not only do you have that high resolution snapshot of each individual cell, but you know how they were organized.” “Previous technologies relied on collecting DNA or RNA from up to millions of cells to make a single measurement,” said Quon. “But if you have to combine all the material you get from millions of cells, you lose a lot of resolution compared to if you could look at each cell individually.” David Slipher/UC DavisSmall science, big hurdles Despite the promises of hi-def, single-cell analysis, there are still some significant challenges to work out. A high-resolution snapshot is just the start.    “Even if we know what changes in the genome at the DNA level raise the risk of Alzheimer’s, what is the exact functional impact of those mutations in the cells?” said Quon. “And where exactly in the brain are the target cells being changed?” While light-years ahead of previous technologies, single-cell genomic sequencing, as is, is still in its nascent stages and riddled with growing pains. “If I collect a bunch of healthy brain samples and do some sequencing, and then I ask someone else to do the same experiment on the same samples in their own lab, even though we’re looking at the same tissues, there’s a huge amount of variation in what you measure at the end of the day,” said Quon, noting that these differences arise not from the underlying biology but from unwanted differences on the human side of the experimentation process. “Our tools are driven a lot by the goal of trying to remove what people call ‘unwanted differences,’” he added. To overcome this, his team hopes to develop algorithms and widely disseminate them to scientists interested in studying genomes.    While light-years ahead of previous technologies, single-cell genomic sequencing, as is, is still in its nascent stages and riddled with growing pains. David Slipher/UC DavisBringing Quon-titative biology to the masses The grant will also help Quon develop programs to train high school, undergraduate and graduate students in quantitative biology practices. “We are developing both classic graduate-level courses to teach people how to use and develop these techniques and technologies, and we’re also working with the Bioinformatics Core and high school outreach programs to try to bring this kind of awareness and skills to the undergraduate and high school level,” he said. Last year, Quon taught a hands-on tutorial on looking at the genome in 3D to about 20 high school students. “It’s pretty clear that there’s a lot of demand for instruction on these kind of skills,” said Quon, who noted that he’s looking into developing a Course-based Undergraduate Research Experience class based around quantitative biology methods. Quon is actively seeking research assistance from students interested in quantitative biology. Interested students can check out his website or email him. Stay Informed! Sign up for our monthly email newsletter  Quon is actively seeking research assistance from students interested in quantitative biology. David Slipher/UC Davis  "> <a class="addthis_button_facebook"></a> <a class="addthis_button_linkedin"></a> <script> var addthis_share = { templates: { twitter: "Thanks to a roughly 5-year, $850,000 CAREER grant from the National Science Foundation, Assistant Professor Gerald Quon will develop next-generation computational tools that will allow researchers to better understand and analyze single-cell genomic data. " } } </script> <a class="addthis_button_twitter"></a> <a class="addthis_button_email"></a> <a class="addthis_button_compact"></a> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><aside class="wysiwyg-feature-block u-width--half u-align--right"><h3 class="wysiwyg-feature-block__title">Quick Summary</h3> <div class="wysiwyg-feature-block__body"> <ul><li><strong><em>A 5-year, $850,000 CAREER grant from the NSF will help Gerald Quon dev</em></strong><strong><em>elop next-generation computational tools to analyze single-cell genomic data</em></strong></li> <li><strong><em>With the grant, Quon also hopes to develop quantitative biology programs for high school, undergraduate and graduate students</em></strong></li> <li><strong><em>Students interested in assisting Quon s</em></strong><strong><em>hould email him at <span><span><span><a href="mailto:gquon@ucdavis.edu"><span><span><span>gquon@ucdavis.edu</span></span></span></a></span></span></span> </em></strong></li> </ul></div> </aside><p><span><span><span><span><span><span>The human body is complex, comprising trillions of cells that work in tandem to promote proper physiological function.</span></span></span></span></span></span></p> <p><span><span><span><span><span><span>But our systems can go awry, leading to the development of a whole host of diseases, like cancer and Alzheimer’s. The keys to unlocking potential therapeutics for these devastating diseases lie in the genome, the proverbial “blueprint for life.” With each passing day, biotechnologies advance, allowing scientists to dissect these diseases at high-definition, single-cell resolutions. </span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“Previous technologies relied on collecting DNA or RNA from up to <em>millions</em> of cells to make a single measurement,” said Assistant Professor Gerald Quon, Department of Molecular and Cellular Biology. “But if you have to combine all the material you get from millions of cells, you lose a lot of resolution compared to if you could look at each cell individually.”</span></span></span></span></span></span></p> </blockquote> <p><span><span><span><span><span><span>“Genomics technologies today are moving towards single-cell resolution,” he added, “and there’s a lot of new challenges associated with data analysis of single-cell genomic data.” </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>One of those challenges is the innumerable data generated from genomic sequencing. It’s gargantuan, more than humans can understand alone. To accomplish this, we need help from new computational tools and cutting-edge hardware to power machine learning.   </span></span></span></span></span></span></p> <figure role="group" class="caption caption-img align-right"><img alt="Tech" data-entity-type="file" data-entity-uuid="793d571f-33cd-4be4-a2e2-f922f67a050e" height="474" src="/sites/g/files/dgvnsk2646/files/inline-images/Gerald-Quon-College-of-Biological-Sciences-UC-Davis-6.jpg" width="316" /><figcaption>To make sense of data generated from genomic sequencing, we need help from cutting-edge hardware to power machine learning. David Sliper/UC Davis   </figcaption></figure><p><span><span><span><span><span><span>Thanks to a roughly 5-year, </span></span></span><a href="https://www.nsf.gov/awardsearch/showAward?AWD_ID=1846559&amp;HistoricalAwards=false"><span><span><span>$850,000 CAREER grant from the National Science Foundation</span></span></span></a><span><span><span>, Quon, who also holds an appointment at the UC Davis Genome Center, will develop next-generation computational tools that will allow researchers to better understand and analyze single-cell genomic data. </span></span></span></span></span></span></p> <h4><span><span><span><strong><span><span><span>New cells on the block</span></span></span></strong></span></span></span></h4> <p><span><span><span><span><span><span>One of Quon’s main goals is to develop computational tools that’ll allow researchers to better understand how cell-to-cell communication affects molecular function and tissue development. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“We want to provide a much higher resolution snapshot of what’s happening in tissues,” said Quon. “For example, in the brain, there’s a lot of variation even between neighboring cells.”   </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>Tissues are much more than just collections of cells individually working on their own. They often communicate with each other in order to coordinate function and development, and so it is important to understand how each cell’s environment impacts its inner workings. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“This is just the beginning,” said Quon. “In the next few years, people are going to release technologies where you actually measure in 2-D and 3-D space where each cell came from. So now not only do you have that high resolution snapshot of each individual cell, but you know how they were organized.” </span></span></span></span></span></span></p> <figure role="group" class="caption caption-img"><img alt="Gerald Quon" data-entity-type="file" data-entity-uuid="6173c76b-c1d8-4252-ad46-4d4c36063345" src="/sites/g/files/dgvnsk2646/files/inline-images/Gerald-Quon-College-of-Biological-Sciences-UC-Davis.jpg" /><figcaption>“Previous technologies relied on collecting DNA or RNA from up to <em>millions</em> of cells to make a single measurement,” said Quon. “But if you have to combine all the material you get from millions of cells, you lose a lot of resolution compared to if you could look at each cell individually.” David Slipher/UC Davis</figcaption></figure><h4><span><span><span><strong><span><span><span>Small science, big hurdles</span></span></span></strong></span></span></span></h4> <p><span><span><span><span><span><span>Despite the promises of hi-def, single-cell analysis, there are still some significant challenges to work out. A high-resolution snapshot is just the start.   </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>“Even if we know what changes in the genome at the DNA level raise the risk of Alzheimer’s, what is the exact functional impact of those mutations in the cells?” said Quon. “And where exactly in the brain are the target cells being changed?” </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>While light-years ahead of previous technologies, single-cell genomic sequencing, as is, is still in its nascent stages and riddled with growing pains.</span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“If I collect a bunch of healthy brain samples and do some sequencing, and then I ask someone else to do the same experiment on the same samples in their own lab, even though we’re looking at the same tissues, there’s a huge amount of variation in what you measure at the end of the day,” said Quon, noting that these differences arise not from the underlying biology but from unwanted differences on the human side of the experimentation process. </span></span></span></span></span></span></p> </blockquote> <p><span><span><span><span><span><span>“Our tools are driven a lot by the goal of trying to remove what people call ‘unwanted differences,’” he added. To overcome this, his team hopes to develop algorithms and widely disseminate them to scientists interested in studying genomes.   </span></span></span></span></span></span></p> <figure role="group" class="caption caption-img"><img alt="Wires" data-entity-type="file" data-entity-uuid="4e300a14-893d-4d9f-ba23-4b76bdc41ef7" src="/sites/g/files/dgvnsk2646/files/inline-images/Gerald-Quon-College-of-Biological-Sciences-UC-Davis-5.jpg" /><figcaption>While light-years ahead of previous technologies, single-cell genomic sequencing, as is, is still in its nascent stages and riddled with growing pains. David Slipher/UC Davis</figcaption></figure><h4><span><span><span><strong><span><span><span>Bringing Quon-titative biology to the masses </span></span></span></strong></span></span></span></h4> <p><span><span><span><span><span><span>The grant will also help Quon develop programs to train high school, undergraduate and graduate students in quantitative biology practices. </span></span></span></span></span></span></p> <blockquote> <p><span><span><span><span><span><span>“We are developing both classic graduate-level courses to teach people how to use and develop these techniques and technologies, and we’re also working with the Bioinformatics Core and high school outreach programs to try to bring this kind of awareness and skills to the undergraduate and high school level,” he said. </span></span></span></span></span></span></p> </blockquote> <p><span><span><span><span><span><span>Last year, Quon taught a hands-on tutorial on looking at the genome in 3D to about 20 high school students. “It’s pretty clear that there’s a lot of demand for instruction on these kind of skills,” said Quon, who noted that he’s looking into developing a </span></span></span><a href="https://fys.ucdavis.edu/cures"><span><span><span>Course-based Undergraduate Research Experience class</span></span></span></a><span><span><span> based around quantitative biology methods. </span></span></span></span></span></span></p> <p><span><span><span><span><span><span>Quon is actively seeking research assistance from students interested in quantitative biology. Interested students can check out his <a href="https://qlab.faculty.ucdavis.edu/">website </a>or <a href="http://gquon@ucdavis.edu">email him</a>.</span></span></span></span></span></span></p> <p class="text-align-center"><a class="btn--lg btn--primary" href="https://biology.ucdavis.edu/form/tell-us-more-about-yourself-2">Stay Informed! Sign up for our monthly email newsletter</a><span><span><span><span><span><span> </span></span></span></span></span></span></p> <figure role="group" class="caption caption-img"><img alt="Gerald Quon" data-entity-type="file" data-entity-uuid="ab03234a-cc2c-4853-88a8-2d03de8f1d1c" src="/sites/g/files/dgvnsk2646/files/inline-images/Gerald-Quon-College-of-Biological-Sciences-UC-Davis-4.jpg" /><figcaption>Quon is actively seeking research assistance from students interested in quantitative biology. David Slipher/UC Davis</figcaption></figure><p> </p> </div> <div class="field field--name-field-sf-article-category field--type-entity-reference field--label-above"> <div class="field__label">Category</div> <div class="field__item"><a href="/articles/genetics-microbiology" hreflang="en">Cellular and Microbiology</a></div> </div> <div class="field field--name-field-sf-tags field--type-entity-reference field--label-above"> <div class="field__label">Tags</div> <div class="field__items"> <div class="field__item"><a href="/tags/molecular-and-cellular-biology" hreflang="en">Department of Molecular and Cellular Biology</a></div> <div class="field__item"><a href="/tags/genome-center" hreflang="en">Genome Center</a></div> <div class="field__item"><a href="/tags/comprehensive-cancer-center" hreflang="en">Comprehensive Cancer Center</a></div> <div class="field__item"><a href="/tags/quantitative-biology" hreflang="en">quantitative biology</a></div> <div class="field__item"><a href="/tags/human-disease" hreflang="en">human disease</a></div> <div class="field__item"><a href="/tags/human-health" hreflang="en">human health</a></div> <div class="field__item"><a href="/tags/national-science-foundation" hreflang="en">National Science Foundation</a></div> <div class="field__item"><a href="/tags/stem-education" hreflang="en">STEM education</a></div> <div class="field__item"><a href="/tags/undergraduate-student-news" hreflang="en">Undergraduate Student News</a></div> <div class="field__item"><a href="/tags/graduate-student-news" hreflang="en">Graduate Student News</a></div> <div class="field__item"><a href="/tags/computer-modeling" hreflang="en">computer modeling</a></div> <div class="field__item"><a href="/tags/computer-science" hreflang="en">computer science</a></div> </div> </div> Wed, 28 Aug 2019 17:53:25 +0000 Greg Watry 3391 at https://biology.ucdavis.edu