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Mike Harms

Mike Harms

Assistant Professor, Chemistry and Biochemistry
Member, IMB

Ph.D. Johns Hopkins University
B.S. Oregon State University

Email
Lab website
Office: Willamette Hall Room 340A
Office Phone: 541-346-9002
Lab: Willamette Hall Room 340
Lab Phone: 541-346-9003

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Research Interests

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.

The S100 protein family as an evolutionary biophysical model

A powerful model system allows deep and nuanced studies that provide insights inaccessible in more complex systems: Drosophila for evolutionary developmental biology, ribonuclease H for protein folding, and—in our case—the S100 family for evolutionary biophysics. The S100s are small (~10 kDa) allosteric calcium binding proteins that ligate calcium and then recruit and regulate specific target proteins. They possess a number of properties that make them an excellent family for asking evolutionary biophysical questions.

Recent publications

(pulled from pubmed)

Recent publications

(pulled from pubmed)

Thermodynamic system drift in protein evolution.
Hart KM, Harms MJ, Schmidt BH, Elya C, Thornton JW, Marqusee S
PLoS Biol 2014 Nov;12(11):e1001994
Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors.
Harms MJ, Eick GN, Goswami D, Colucci JK, Griffin PR, Ortlund EA, Thornton JW
Proc Natl Acad Sci U S A 2013 Jul 9;110(28):11475-80
Evolution of minimal specificity and promiscuity in steroid hormone receptors.
Eick GN, Colucci JK, Harms MJ, Ortlund EA, Thornton JW
PLoS Genet 2012;8(11):e1003072
Arginine residues at internal positions in a protein are always charged.
Harms MJ, Schlessman JL, Sue GR, García-Moreno B
Proc Natl Acad Sci U S A 2011 Nov 22;108(47):18954-9
Analyzing protein structure and function using ancestral gene reconstruction.
Harms MJ, Thornton JW
Curr Opin Struct Biol 2010 Jun;20(3):360-6
Protein evolution by molecular tinkering: diversification of the nuclear receptor superfamily from a ligand-dependent ancestor.
Bridgham JT, Eick GN, Larroux C, Deshpande K, Harms MJ, Gauthier ME, Ortlund EA, Degnan BM, Thornton JW
PLoS Biol 2010 Oct 5;8(10)
The pK(a) values of acidic and basic residues buried at the same internal location in a protein are governed by different factors.
Harms MJ, Castañeda CA, Schlessman JL, Sue GR, Isom DG, Cannon BR, García-Moreno E B
J Mol Biol 2009 May 29;389(1):34-47
A buried lysine that titrates with a normal pKa: role of conformational flexibility at the protein-water interface as a determinant of pKa values.
Harms MJ, Schlessman JL, Chimenti MS, Sue GR, Damjanović A, García-Moreno B
Protein Sci 2008 May;17(5):833-45
Laser light-scattering evidence for an altered association of beta B1-crystallin deamidated in the connecting peptide.
Harms MJ, Wilmarth PA, Kapfer DM, Steel EA, David LL, Bächinger HP, Lampi KJ
Protein Sci 2004 Mar;13(3):678-86