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Projects
The Harms Lab studies protein evolution and biophysics using experimental and computational methods.
Current Members
![](img/headshots/harms_circle_150x150.png)
Mike
Harms
Principal Investigator
Favorite part of job: trainees waving graphs in office.
![](img/headshots/muyskens_circle_150x150.png)
Jon
Muyskens
Lab Manager
Developmental biologist turned evolutionary biochemist.
![](img/headshots/shavlik_circle_150x150.png)
Michael
Shavlik
PhD student
Experimental studies of "might-have-been" evolutionary trajectories
![](img/headshots/orlandi_circle_150x150.png)
Kona
Orlandi
PhD student
Early evolution of TLR4
![](img/headshots/lehmann_circle_150x150.png)
Lauren
Lehmann
PhD student
How does S100A9 interact with TLR4?
![](img/headshots/phillips_circle_150x150.png)
Sophia
Phillips
PhD student
Evolution of S100A9 proinflammatory activity
![](img/headshots/sanchez-borbon_circle_150x150.png)
Jose
Sanchez-Borbon
PhD student
How did the CD14 LPS binding site evolve?
Previous Members
(in reverse order of when each left)
![](img/headshots/perez_circle_150x150.png)
Luis
Perez
PhD student
Studies of protein sequence space
![](img/headshots/yin_circle_150x150.png)
JJ
Yin
Undergrad researcher
Evolution of S100A9 proinflammatory activity
![](img/headshots/morrison_circle_150x150.png)
Anneliese
Morrison
PhD, 2021
Research scientist with Absci
![](img/headshots/murawsky_circle_150x150.png)
Hannah
Murawsky
Undergrad, 2021
Biochemistry (honors thesis), med student at UNLV
![](img/headshots/wonderlick_circle_150x150.png)
Daria
Wonderlick
Undergrad, 2021
Biochemistry (honors thesis), PhD student at Stanford
![](img/headshots/harman_circle_150x150.png)
Joseph
Harman
PhD, 2020
Postdoc with David Baker, U Washington
![](img/headshots/connor_circle_150x150.png)
Patrick
Connor
Undergrad
Biochemistry, med student at Iowa
![](img/headshots/warren_circle_150x150.png)
Gus
Warren
Undergrad
Biochemistry, research tech at OHSU
![](img/headshots/frantz_circle_150x150.png)
Nick
Frantz
Masters, 2020
Biochemistry
![](img/headshots/anderson_circle_150x150.png)
Jeremy
Anderson
Postdoc
Data scientist, Travelers Insurance
![](img/headshots/dorrell_circle_150x150.png)
Genevieve
Dorrell
Undergrad
Marine Biology
![](img/headshots/goldbach_circle_150x150.png)
Leander
Goldbach
Visiting Masters Student
![](img/headshots/loes_circle_150x150.png)
Andrea
Loes
PhD, 2018
Lab manager, Bloom Lab, Fred Hutch
![](img/headshots/sailer_circle_150x150.png)
Zach
Sailer
PhD, 2018
Software developer, Apple
![](img/headshots/wong_circle_150x150.png)
Caitlyn
Wong
Undergrad
Biochemistry (honors thesis), med student at OHSU
![](img/headshots/wheeler_circle_150x150.png)
Luke
Wheeler
PhD, 2017
Postdoc with Stacey Smith, UC Boulder
![](img/headshots/shi_circle_150x150.png)
Ran
Shi
Undergrad
Biochemistry, PhD student at U. Georgia
![](img/headshots/rickett_circle_150x150.png)
Bram
Rickett
Undergrad
Biochemistry (honors thesis)
![](img/headshots/duvvuri_circle_150x150.png)
Hiranmayi
Duvvuri
Undergrad
Biochemistry
![](img/headshots/heaphy_circle_150x150.png)
Maureen
Heaphy
Undergrad
Marine Biology
![](img/headshots/smith_circle_150x150.png)
Jaclyn
Smith
Undergrad
Biology
Publications
An experimental demonstration of ensemble epistasis in the lac repressor
bioRxiv
Disentangling contact and ensemble epistasis in a riboswitch
Biophysical Journal
Higher-order interactions shape microbial interactions as microbial community complexity increases
Scientific Reports 12: 22640
Topiary: pruning the manual labor from ancestral sequence reconstruction
Protein Science
Evolution avoids a pathological stabilizing interaction in the immune protein S100A9
PNAS 119 (41) e2208029119
Ensemble epistasis: thermodynamic origins of non-additivity between mutations
Genetics 219(1):iyab105
A conserved folding nucleus sculpts the free energy landscape of bacterial and archaeal orthologs from a divergent TIM barrel family
PNAS 118(17):e2019571118
Evolutionary conservation of structural and functional coupling between the BRM AT-hook and bromodomain
Journal of Molecular Biology 166845
Exploring the evolutionary history of kinetic stability in the alpha-lytic protease family
Biochemistry 60(3):170–181
Were ancestral proteins less specific?
Molecular Biology and Evolution msab019
Identification and characterization of zebrafish Tlr4 co-receptor Md-2
Journal of Immunology 206(5):1046-1057
Learning Peptide Recognition Rules for a Low Specificity Protein
Protein Science 29:2259 –2273
Inferring a complete genotype-phenotype map from a small number of measured phenotypes
PLOS Computational Biology e1008243
Evolution of multifunctionality through a pleiotropic substitution in the innate immune protein S100A9
eLife 9:e54100
Zinc-independent activation of Toll-like receptor 4 by S100A9
bioRxiv
Skeletal geometry and nice transitions restore organ size and shape during zebrafish fin regeneration
bioRxiv
Tracing the evolution of novel features of human Toll-like receptor 4
Protein Science 28(7):1350-1358
pytc: open source python software for global analyses of isothermal titration calorimetry data
Biochemistry 57(18):2578–2583
Coevolution of the Toll-Like Receptor 4 complex with calgranulins and lipopolysaccharide
Frontiers in Immunology
Conservation of specificity in two low-specificity proteins
Biochemistry 57(5):684-695
Enzymes emerge by upcycling [News & Views]
Nature Chemical Biology 14:526-527
Ca2+ and Cu2+ bind independently to human S100A5
BMC Biophysics 10:8
Molecular ensembles make evolution unpredictable
PNAS 114(45):11938-11943
High-order epistasis shapes evolutionary trajectories
PLOS Computational Biology
Detecting high-order epistasis in nonlinear genotype-phenotype maps
Genetics 205(3):1079-1088
Robustness of reconstructed ancestral protein functions to statistical uncertainty
Molecular Biology and Evolution 34 (2):247-261
Multiple evolutionary origins of ubiquitous Cu2+ and Zn2+ binding in the S100 protein family
PLOS ONE 11(10): e0164740
Following the folding trajectory of RNases H over evolutionary time: a trend towards kinetic stability
PNAS 113(46):13045-13050
Ancient protein thermostability and specificity [Invited Review]
Current Opinions in Structural Biology 38:37-43
Thermodynamic system drift in the evolution of protein thermostability
PLOS Biology 12(11):e1001994
Biophysical basis for historical contingency in glucocorticoid receptor evolution
Nature 512:203-207
Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors
PNAS 110(28):11475-11480
Evolutionary biochemistry: Revealing the historical and physical causes of protein function
Nature Reviews Genetics 14(8):559-571
Resurrection of an Urbilaterian U1A/U2B''/SNF protein
Journal of Molecular Biology 425(20):3846–3862
Evolution of minimal specificity in the steroid receptors
PLOS Genetics 8(11):e1003072
Arginine is ionized at internal positions in a protein
PNAS 108(47):18954-9
Protein evolution by molecular tinkering: diversification of the nuclear receptor superfamily from a ligand-dependent ancestor
PLOS Biology 8(10):e1000497
Analyzing protein structure and function using ancestral gene reconstruction
Current Opinions in Structural Biology 20(3):360-366
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
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
How sequence defines structure: a crystallographic map of DNA structure and conformation
PNAS 102(20):7157-7162
Laser light-scattering evidence for an altered association of βB1-crystallin deamidated in the connecting peptide
Protein Science 13:678-686
Location
Location on campus
Mike's office: Willamette 340A
Lab: Willamette 340, 342
Address
Harms Lab
Institute for Molecular Biology
1229 University of Oregon
Eugene, OR 97403-1229
Phone
541-346-9003