- Molecular and Cellular Biology
Microtubules are dynamic protein polymers that generate forces inside eukaryotic cells that lead to transformations to divide, develop, or crawl. Microtubules assemble from basic building blocks, known as alpha beta (αβ) tubulin dimers, which polymerize head-to-tail to form protofilaments, using the energy of Guanosine 3,5 Triphosphate (GTP) binding and hydrolysis; These protofilaments associate laterally enclosing a tube-like structure-- a microtubule. Tubulin polymerization is driven by its high concentration inside the cytoplasm and activates GTP hydrolysis upon its incorporation into microtubule lattices at their ends. However, during stochastic reversals, called catastrophes, tubulin protofilaments stop polymerizing and peel-out to rapidly dissemble microtubules. The Al-Bassam laboratory studies conserved multi-subunit molecular machines drive soluble αβ-tubulin heterodimers biogenesis inside cells, and how αβ-tubulins are polymerized or depolymerized at microtubule ends. These molecular machines are found in all eukaryotic organisms and act as αβ-tubulin “factories”, microtubule “polymerases” or “depolymerases” to accelerate specific aspects of microtubule dynamics inside cells. We also study the mechanism and regulation of kinesin motor proteins involved in organizing microtubules during bipolar spindle assembly during mitosis. We are focused on deciphering mechanisms of molecular machines and how they cooperate during cell division and development. We combine biochemistry with structural biology approaches such as cryo-electron microscopy (cryo-EM) and X-ray crystallography, and high-resolution single molecule total internal reflection microscopy reconstitution studies to gain a full mechanistic view of structure in relation to function. Combining these powerful approaches bridges a large resolution range between the αβ-tubulin structure and its polymerization into microtubules, which span from micro-meter to the sub-nano-meter scales. These approaches allow us to link atomic organization and architectures of these molecular machines with αβ-tubulin and their conformational changes with their unique functional states at microtubule ends.
Graduate Program Affiliations
- 1998 B.S. in Biochemistry, California State University, Long Beach
- 2004 Ph.D. in Biochemistry and Biophysics, Scripps Research Institute
- 2011 Post Doctoral Fellow, Harvard Medical School