个人简介

B.S., Oregon State University, 2004. Ph.D. Johns Hopkins University, 2008. Postdoctoral: Postdoctoral: University of Oregon (2009-2013; Joe Thornton). At Oregon since 2013.

研究领域

Biochemistry/Molecular Biology/Biophysics

The overarching goal of the Harms lab is to understand the relationship between the biophysical properties of proteins and their evolution. Why do proteins with certain sequences and physical properties—out of a huge space of possibilities—occur? How do the physical properties of proteins shape their evolutionary trajectories? Which protein features are optimized by evolution, and which are determined by chance? How does a blind evolutionary process assemble complex features like ligand binding sites or allosteric regulation? Is protein evolution predictable or stochastic? To answer these (and other) questions, we take a synthetic approach, combining concepts and methodologies from classical biophysics and evolutionary biology. We employ advanced phylogenetics techniques (including ancestral protein resurrection), high-throughput experimental screens, and rigorous experimental/computational biophysical approaches to directly study the interplay of evolutionary and biophysical forces in generating both the complexity and diversity of natural proteins.

近期论文

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Hart KM, Harms MJ, Schmidt BH, Elya C, Thornton JW, Marqusee S. "Thermodynamic System Drift in Protein Evolution." (2014). PLoS Biology. 12(11):e1001994 Harms MJ & Thornton JW. "Historical contingency and its biophysical basis in glucocorticoid receptor evolution." (2014). Nature. doi:10.1038/nature13410 Harms MJ & Thornton JW. "Evolutionary biochemistry: Revealing the historical and physical causes of protein function." (2013). Nature Reviews Genetics. 14(8):559-571 Harms MJ, Eick GN, Goswami D, Colucci JK, Griffin PR, Ortlund EA, Thornton JW. "Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors." (2013) Proceedings of the National Academy of Sciences, USA. 110(28):11475–11480 Williams SG, Harms MJ, Hall KB. "Resurrection of an Urbilaterian U1A/U2B"/SNF protein." (2013) Journal of Molecular Biology. 425(20):3846–3862 Eick GN, Colucci J, Harms MJ, Ortlund EA, Thornton JW. "Evolution of minimal specificity in the steroid receptors." (2012) PLoS Genetics. 8(11):e1003072 Harms MJ, Schlessman JL, Sue GR, García-Moreno E. B. "Arginine is ionized at internal positions in a protein." (2011) Proceedings of the National Academy of Sciences, USA. 108(47):18954-9. Listed as "Must Read" on Faculty of 1000. Bridgham JT, Eick G, Larroux C, Deshpande K, Harms MJ, Gauthier MEA, Ortlund EA, Degnan BM, Thornton JW (2010). "Protein evolution by molecular tinkering: diversification of the nuclear receptor superfamily from a ligand-dependent ancestor." PLoS Biology 8(10): e1000497 Harms MJ, Thornton JW. (2010). "Analyzing protein structure and function using ancestral gene reconstruction." Current Opinions in Structural Biology. 20(3):360-366. Harms MJ, Castañeda CA, Schlessman JL, Sue GR, Isom DG, Cannon BR, García- Moreno E. B. (2009). "The pKa values of acidic and basic residues buried at the same internal location in a protein are governed by different factors." Journal of Molecular Biology. 389:34-47. Listed as "Must Read" on Faculty of 1000. Thesis. Harms, MJ. "Molecular determinants of pKa values of internal ionizable groups in staphylococcal nuclease." The Johns Hopkins University, ProQuest, UMI Dissertations Publishing, 2009. 3339887. Harms MJ, Schlessman JL, Chimenti MS, Sue GR, Damjanovic A, García-Moreno E. B. (2008). "A buried lysine that titrates with a normal pKa: Role of conformational flexibility at the protein–water interface as a determinant of pKa values." Protein Science. 17:833-845. Hays FA, Teegarden A, Jones ZJR, Harms MJ, Raup D, Watson F, Cavaliere E, Ho PS. (2005). "How sequence defines structure: a crystallographic map of DNA structure and conformation." Proceedings of the National Academy of Sciences USA. 102(20):7157-7162. Harms MJ, Wilmarth PA, Kapfer DM, Steel EA, David LL, Bachinger HP, Lampi KJ. (2003). "Laser light-scattering evidence for an altered association of βB1- crystallin deamidated in the connecting peptide." Protein Science. 13:678-686.