Michael A Savageau

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Position Title
Distinguished Professor Emeritus

Unit
Department of Biomedical Engineering
Department of Microbiology and Molecular Genetics

228, Briggs Hall
Bio

Profile Introduction

Savageau’s research aims to elucidate function, design and evolution of natural and synthetic molecular systems. His Group focuses on development of general mathematical and computational methods, and on their application to specific molecular systems.

Research Interests

Developing mathematical systems biology, identifying design principles in molecular biology, developing a computationally assisted ‘system design space methodology’ for relating genotype and environment to the phenotype of complex biochemical systems.

Current development projects:

Software tools enabling a new ‘phenotype-centric’ modeling strategy

Current application projects:

Regulatory networks for integration of bacterial catabolism and behavior in complex chemotaxis

Molecular mechanisms for realizing the switch to xylem cell development in plants

Cognate amino acid signatures in the biosynthetic enzymes of organisms in the human microbiome.  

Graduate Group Affiliations

Applied Mathematics

Biomedical Engineering

Microbiology

Specialties / Focus

Biochemistry

Computational Biology

Developmental Biology

Gene Regulation

Mathematical Biology

Metabolism

Microbiome

Modeling

Molecular Biology

Molecular Genetics

Labs

230 Briggs Hall

            Postdoctoral Scholar: Miguel Ángel Valderrama Gómez

Honors and Awards

1976-77      Guggenheim Fellow

1976-77      Fulbright Senior Research Fellow, Göttingen, Germany

1983-84      Fellow, The John Curtin School of Medical Research, Canberra, Australia

1990-94      Senior Fellow, Michigan Society of Fellows

1993-95      Foundation for Microbiology Lecturer

1996            Fellow, American Association for the Advancement of Science

2001            Harold R. Johnson Diversity Service Award, The University of Michigan

2002           Nicolas Rashevsky Distinguished University Professor, The University of

                    Michigan

2002           Guest, Institut des Hautes Études Scientifiques, Bures-sur-Yvette, France

2002           Chair Recognition Award, The University of Michigan Medical School

2002           Member, National Academies of Science, National Academy of Medicine

                     (formerly the Institute of Medicine)

2003           Moore Distinguished Scholar, California Institute of Technology

2003           Distinguished Professor, University of California, Davis

2006           Hall of Honor, University of Michigan Medical School 

2006           79thJosiah Willard Gibbs Lecturer, American Mathematical Society

2007           Fellow, American Institute for Medical and Biological Engineering

2008           Outstanding Senior Research Faculty Award, College of Engineering,

                     University of California, Davis

2009           Stanislaw Ulam Distinguished Scholar Award, Center for Nonlinear Studies,

                     Los Alamos National Laboratory, Los Alamos, New Mexico.

2011             Honorary Doctor of Science, Universitat de Lleida, Spain

2013            Fellow, Institute of Electrical and Electronic Engineers

2013            Roger E. Koeppe Lecture, Department of Biochemistry and Molecular Biology,

                    Oklahoma State University

2013            The Michael A. Savageau Collegiate Professorship in Computational

                    Medicine and Bioinformatics, permanently endowed by the University of

                    Michigan

2016            F1000 Prime Faculty, Systems & Network Biology Section

2017            Fellow, American Academy of Microbiology

Professional Societies

American Association for the Advancement of Science (Fellow) 

American Institute for Medical and Biological Engineering (Fellow) 

American Society for Microbiology (Fellow)

Biomedical Engineering Society

Institute of Electrical and Electronic Engineers (Fellow) 

Society for Mathematical Biology

Degrees

2011 PhD Science Honoris Causa Universitat de Lieida Spain

1967 PhD Cell Physiology and Systems Engineering (EE) Stanford University

1963 MS Physiology and Systems Engineering (EE) University of Iowa

1962 BS Engineering Science (EE) University of Minnesota (Highest honors)

Publications

Valderrama Gómez MA, Parales RE, Savageau MA (2018) Phenotype-centric modeling for elucidation of biological design principles. J. Theoret. Biol. (doi/10.1016/j.jtbi.2018.07.009).

Lee H, Lomnitz JG, Savageau MA (2018) Mathematically controlled comparison for elucidating biological design principles, in “Quantitative Biology: Computational Methods and Examples", Eds. Hlavacek W, Munsky B, Tsimring L., pp. 247-270.

Lomnitz JG, Savageau MA (2016b) Rapid discrimination among putative mechanistic models of biochemical systems. Sci. Rep. 6, 32375; doi: 10.1038/srep32375.

Lomnitz JG, Savageau MA (2016a) Design Space Toolbox V2: Automated software enabling a novel phenotype-centric modeling strategy for natural and synthetic biological systems. Front. Genet. 7, 118.

Lomnitz JG, Savageau MA (2015) Elucidating the genotype-phenotype map by automatic enumeration and analysis of the phenotypic repertoire. npj Systems Biology and Applications 1, 15003; doi:10.1038/npjsba.2015.3.  

Fasani RA, Savageau MA (2015) Unrelated toxin-antitoxin systems cooperate to induce persistence, Interface. 12(108) (doi: 10.1098/rsif.2015.0130).  

Tolla DA, Kiley PJ, Lomnitz JG, Savageau MA 2015) Design Principles of a Conditional Futile Cycle Exploited for Regulation, Molecular BioSystmes, 11(7): 1841-1849 (doi: 10.1039/C5MB00055F).  

Fasani RA, and Savageau MA (2015) Unrelated toxin-antitoxin systems cooperate to induce persistence, Interface. 12(108), (doi: 10.1098/rsif.2015.0130).  

Savageau MA, Lomnitz JG (2015) Deconstructing Complex Nonlinear Models in System Design Space. in“Discrete and Topological Models in Molecular Biology”, N. Jonoska and M. Saito, Eds., Springer-Verlag, Berlin, pp. 475-506. 

Fasani RA, Savageau MA (2014) Evolution of a genome encoded bias in amino acid biosynthetic pathways is a potential indicator of amino acid dynamics in the environment.  Molecular Biology and Evolution. 31(11):2865-2878 (doi:10.1093/molbev/msu225).

Lomnitz JG, Savageau MA (2014) Strategy revealing phenotypic differences among oscillator designs.  ACS Synthetic Biology, 3, 686-701.

Fasani RA, Savageau MA (2013) Molecular mechanisms of multiple toxin-antitoxin systems are coordinated to govern the persister phenotype. Proc Natl Acad Sci USA., doi/10.1073/pnas.1301023110.

Lomnitz JG, Savageau MA (2013) Phenotypic deconstruction of gene circuitry, Chaos June:23(2):025108 (doi/10.1063/1.4809776).

Williams K, Savageau MA, Blumenthal RM (2013) A bistable hysteretic switch in an activator-repressor regulated restriction-modification system, Nucl. Acids Res. 41(12):6045-6057.

Savageau MA (2013b) System Design Principles, inQuantitative Biology: From Molecular to Cellular Behavior,” ME Wall, Ed., Taylor and Francis Group, Boca Raton, FL, pp. 23-49.  

Balderas-Martínez YI, Savageau MA, Salgado H, Pérez-Rueda E, Morett E, Collado-Vides J (2013) Transcription Factors in Escherichia coliPrefer the HoloConformation. PLoS ONE June: 8(6): e65723. doi:10.1371/journal.pone.0065723.

Savageau MA (2013a) Phenotypes and Design Principles in System Design Space. In“Handbook of Systems Biology,” AJM Walhout, M Vidal and J Dekker, Eds., Elsevier, San Diego, CA, pp. 287-310.  

Moura A, Savageau MA, Alves R (2013) Relative amino acid composition signatures of organisms and environments. PLoS ONE  8(10): e77319. doi:10.1371/journal.pone.0077319.

Martínez-Antonio A, Lomnitz JG, Sandoval S, Aldana M, Savageau MA (2012) Regulatory design governing progression of population growth phases in bacteria, PLoS ONE 7(2): e30654. doi:10.1371/journal.pone.0030654. 

Tolla DA, Savageau MA (2011) Phenotypic repertoire of the FNR regulatory network in Escherichia coli.Mol Microbiol. Jan;79(1):149-65.  

Savageau MA (2011) Design of the lac gene circuit revisited. Math Biosci. May;231(1):19-38. Epub 2011 Mar 21. PubMed PMID: 21414326.

Fasani RA, Savageau MA (2010) Automated construction and analysis of the design space for biochemical systems.Bioinformatics. Oct 15;26(20):2601-9.

Tolla DA, Savageau MA (2010) Regulation of aerobic-to-anaerobic transitions by the FNR cycle in Escherichia coli.J Mol Biol. Apr 9;397(4):893-905. Epub 2010 Feb 12. PubMed PMID: 20156450; PubMed Central PMCID: PMC2867928.

Coelho PM, Salvador A, Savageau MA (2010) Relating mutant genotype to phenotype via quantitative behavior of the NADPH redox cycle in human erythrocytes.PLoS One. Sep 28;5(9). pii: e13031. PubMed PMID: 20927393; PubMed Central PMCID: PMC2946920.

Reams AB, Kofoid E, Savageau MA, Roth JR (2010) Duplication frequency in a population of Salmonella enterica rapidly approaches steady state with or without recombination.Genetics. Apr;184(4):1077-94. Epub 2010 Jan 18. PubMed PMID: 20083614; PubMed Central PMCID: PMC2865909.

Savageau MA, Coelho PM, Fasani RA, Tolla DA, Salvador A.(2009) Phenotypes and tolerances in the design space of biochemical systems.Proc Natl Acad Sci U S A.  Apr 21;106(16):6435-40. 

Coelho PM, Salvador A, Savageau MA (2009) Quantifying global tolerance of biochemical systems: design implications for moiety-transfer cycles.PLoS Comput Biol. Mar;5(3):e1000319.

Savageau MA (2009) "Biochemical Systems Analysis:  A Study of Function and Design in Molecular Biology," 40thAnniversary Edition [A reprinting of the original edition published by Addison-Wesley, Reading, Mass., 1976].

Savageau MA, Fasani RA (2009) Qualitatively distinct phenotypes in the design space of biochemical systems.FEBS Lett. Dec 17;583(24):3914-22. Epub . Review. PubMed PMID: 19879266; PubMed Central PMCID: PMC2888490.

Igoshin OA, Alves R, Savageau MA (2008) Hysteretic and graded responses in bacterial two-component signal transduction.Mol Microbiol. Jun;68(5):1196-215. Epub 2008 Mar 19. PubMed PMID: 18363790.

Igoshin OA, Brody MS, Price CW, Savageau MA (2007) Distinctive topologies of partner-switching signaling networks correlate with their physiological roles.J Mol Biol. Jun 22;369(5):1333-52. Epub 2007 Apr 14. PubMed PMID: 17498739; PubMed Central PMCID: PMC2727513.

Igoshin OA, Price CW, Savageau MA (2006) Signaling network with a bistable hysteretic switch controls developmental activation of the sFtranscription factorin BacillussubtilisMol. Microbiol. 61, 165-184.

Salvador A, Savageau MA (2006) Evolution of enzymes in a series is driven by dissimilar functional demands, Proc. Natl. Acad. Sci. USA 103, 2226-2231.  

Alves R,Savageau MA (2005) Evidence of selection for low cognate amino-acid bias in amino-acid biosynthetic enzymes, Mol. Microbiol. 56, 1017–1034.  

Wall ME, Hlavacek WS, Savageau MA (2004) Design of gene circuits: Lessons from bacteria, Nature Reviews Genetics5, 34-42(2004). 

Atkinson MR, Savageau MAMyers JT,Ninfa AJ (2003) Development of genetic circuitry exhibiting toggle switch or oscillatory behavior in Escherichia coliCell 113, 597-607.  

Salvador A, Savageau MA (2003) Quantitative evolutionary design of glucose 6-phosphate dehydrogenase expression in human erythrocytes, Proc. Natl. Acad. Sci. USA 100, 14463-14468.  

Alves R, Savageau MA (2003) Comparative analysis of prototype two-component systems with either bifunctional or monofunctional sensors:  Differences in molecular structure and physiological function, Mol. Microbiol. 48, 25-51.  

Wall ME, Hlavacek WS, Savageau MA (2003) Design principles for regulator gene expression in a repressible gene circuit, J. Mol. Biol. 332, 861-876.  

Savageau MA (2001) Design principles for elementary gene circuits: Elements, methods, and examples, Chaos11, 142-159.  

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