Harms Lab

Evolutionary biochemistry @UO

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Values

Our goal is for the lab to be a place of human thriving. In a research group, human thriving means doing excellent and impactful science. It also means that each lab member is healthy and growing as a person, that the work we do makes the world a better place, and that we strive to make the scientific enterprise more inclusive and diverse.

Details...




Projects

The Harms Lab studies protein evolution and biophysics using experimental and computational methods.




Current Members

Mike
Harms

Principal Investigator

Favorite part of job: trainees waving graphs in office.


Jon
Muyskens

Lab Manager

Developmental biologist turned evolutionary biochemist.


Michael
Shavlik

PhD student

Experimental studies of "might-have-been" evolutionary trajectories


Kona
Orlandi

PhD student

Early evolution of TLR4


Lauren
Lehmann

PhD student

How does S100A9 interact with TLR4?


Sophia
Phillips

PhD student

Evolution of S100A9 proinflammatory activity


Jose
Sanchez-Borbon

PhD student

How did the CD14 LPS binding site evolve?







Previous Members

(in reverse order of when each left)

Luis
Perez

PhD student

Studies of protein sequence space


JJ
Yin

Undergrad researcher

Evolution of S100A9 proinflammatory activity


Anneliese
Morrison

PhD, 2021

Research scientist with Absci


Hannah
Murawsky

Undergrad, 2021

Biochemistry (honors thesis), med student at UNLV


Daria
Wonderlick

Undergrad, 2021

Biochemistry (honors thesis), PhD student at Stanford


Joseph
Harman

PhD, 2020

Postdoc with David Baker, U Washington


Patrick
Connor

Undergrad

Biochemistry, med student at Iowa


Gus
Warren

Undergrad

Biochemistry, research tech at OHSU


Nick
Frantz

Masters, 2020

Biochemistry


Jeremy
Anderson

Postdoc

Data scientist, Travelers Insurance


Genevieve
Dorrell

Undergrad

Marine Biology


Leander
Goldbach

Visiting Masters Student


Andrea
Loes

PhD, 2018

Lab manager, Bloom Lab, Fred Hutch


Zach
Sailer

PhD, 2018

Software developer, Apple


Caitlyn
Wong

Undergrad

Biochemistry (honors thesis), med student at OHSU


Luke
Wheeler

PhD, 2017

Postdoc with Stacey Smith, UC Boulder


Ran
Shi

Undergrad

Biochemistry, PhD student at U. Georgia


Bram
Rickett

Undergrad

Biochemistry (honors thesis)


Hiranmayi
Duvvuri

Undergrad

Biochemistry


Maureen
Heaphy

Undergrad

Marine Biology


Jaclyn
Smith

Undergrad

Biology







Publications

preprint

An experimental demonstration of ensemble epistasis in the lac repressor

bioRxiv

Morrision AJ, Harms MJ
in press

Disentangling contact and ensemble epistasis in a riboswitch

Biophysical Journal

Wonderlick DR, Widom JR, Harms MJ
2022

Higher-order interactions shape microbial interactions as microbial community complexity increases

Scientific Reports 12: 22640

Morin MA, Morrison AJ, Harms MJ, Dutton RJ
2022

Topiary: pruning the manual labor from ancestral sequence reconstruction

Protein Science

Orlandi KN, Phillips SR, Sailer ZR, Harman JL, Harms MJ
2022

Evolution avoids a pathological stabilizing interaction in the immune protein S100A9

PNAS 119 (41) e2208029119

Harman JL, Reardon PN, Costello SM, Warren GD, Phillips SR, Connor PJ, Marqusee S, Harms MJ
2021

Ensemble epistasis: thermodynamic origins of non-additivity between mutations

Genetics 219(1):iyab105

Morrison AJ, Wonderlick DR, Harms MJ
2021

A conserved folding nucleus sculpts the free energy landscape of bacterial and archaeal orthologs from a divergent TIM barrel family

PNAS 118(17):e2019571118

Jain R, Muneeruddin K, Anderson J, Harms MJ,Shaffer SA,Matthews CR
2021

Evolutionary conservation of structural and functional coupling between the BRM AT-hook and bromodomain

Journal of Molecular Biology 166845

Lupo BE, Chu P, Harms MJ; Morrison EA; Musselman CA
2021

Exploring the evolutionary history of kinetic stability in the alpha-lytic protease family

Biochemistry 60(3):170–181

Nixon CF, Lim SA, Sailer ZR, Zheludev IN, Gee CL, Kelch BA, Harms MJ, Marqusee S
2021

Were ancestral proteins less specific?

Molecular Biology and Evolution msab019

Wheeler LC & Harms MJ
2021

Identification and characterization of zebrafish Tlr4 co-receptor Md-2

Journal of Immunology 206(5):1046-1057

Loes AN, Hinman MN, Farnsworth DR, Miler AC, Guillemin K, Harms MJ
2020

Learning Peptide Recognition Rules for a Low Specificity Protein

Protein Science 29:2259 –2273

Wheeler LC, Perkins, Wong CE, Harms MJ
2020

Inferring a complete genotype-phenotype map from a small number of measured phenotypes

PLOS Computational Biology e1008243

Sailer ZS, Shafik SH, Summers RL, Joul A, Patterson-Robert A, Martin RE, Harms MJ
2020

Evolution of multifunctionality through a pleiotropic substitution in the innate immune protein S100A9

eLife 9:e54100

Harman JL, Loes AN, Warren GD, Heaphy MC, Lampi KJ, Harms MJ
preprint

Zinc-independent activation of Toll-like receptor 4 by S100A9

bioRxiv

Loes AN, Shi R, Harms MJ
preprint

Skeletal geometry and nice transitions restore organ size and shape during zebrafish fin regeneration

bioRxiv

Stewart S, Yette GA, Le Bleu HK, Henner AL, Braunstein JA, Chehab JW, Harms MJ, Stankunas K
2019

Tracing the evolution of novel features of human Toll-like receptor 4

Protein Science 28(7):1350-1358

Anderson JA, Loes AN, Shi R, Waddell GL, Harms MJ
2018

pytc: open source python software for global analyses of isothermal titration calorimetry data

Biochemistry 57(18):2578–2583

Duvuuri H, Wheeler LW, Harms MJ
2018

Coevolution of the Toll-Like Receptor 4 complex with calgranulins and lipopolysaccharide

Frontiers in Immunology

Loes AN, Bridgham JT, Harms MJ
2018

Conservation of specificity in two low-specificity proteins

Biochemistry 57(5):684-695

Wheeler LW, Anderson JA, Morrison AJ, Wong CE, Harms MJ
2018

Enzymes emerge by upcycling [News & Views]

Nature Chemical Biology 14:526-527

Harms MJ
2017

Ca2+ and Cu2+ bind independently to human S100A5

BMC Biophysics 10:8

Wheeler LW, Harms MJ
2017

Molecular ensembles make evolution unpredictable

PNAS 114(45):11938-11943

Sailer ZS, Harms MJ
2017

High-order epistasis shapes evolutionary trajectories

PLOS Computational Biology

Sailer ZS, Harms MJ
2017

Detecting high-order epistasis in nonlinear genotype-phenotype maps

Genetics 205(3):1079-1088

Sailer ZS, Harms MJ
2017

Robustness of reconstructed ancestral protein functions to statistical uncertainty

Molecular Biology and Evolution 34 (2):247-261

Eick GN, Bridgham JT, Anderson DP, Harms MJ, Thornton JM
2016

Multiple evolutionary origins of ubiquitous Cu2+ and Zn2+ binding in the S100 protein family

PLOS ONE 11(10): e0164740

Wheeler LW, Donor M, Prell JS, Harms MJ
2016

Following the folding trajectory of RNases H over evolutionary time: a trend towards kinetic stability

PNAS 113(46):13045-13050

Li SM, Hart KM, Harms MJ, Marqusee S
2016

Ancient protein thermostability and specificity [Invited Review]

Current Opinions in Structural Biology 38:37-43

Wheeler LW, Li SM, Marqusee S, Harms MJ
2014

Thermodynamic system drift in the evolution of protein thermostability

PLOS Biology 12(11):e1001994

Hart KM, Harms MJ, Schmidt BH, Thornton JW, Marqusee S
2014

Biophysical basis for historical contingency in glucocorticoid receptor evolution

Nature 512:203-207

Harms MJ, Thornton JW
2013

Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors

PNAS 110(28):11475-11480

Harms MJ, Eick GN, Colucci J, Ortlund EA, Thornton JW
2013

Evolutionary biochemistry: Revealing the historical and physical causes of protein function

Nature Reviews Genetics 14(8):559-571

Harms MJ, Thornton JW
2013

Resurrection of an Urbilaterian U1A/U2B''/SNF protein

Journal of Molecular Biology 425(20):3846–3862

Williams SG, Harms MJ, Hall KB
2012

Evolution of minimal specificity in the steroid receptors

PLOS Genetics 8(11):e1003072

Eick GN, Colucci J, Harms MJ, Ortlund EA, Thornton JW
2011

Arginine is ionized at internal positions in a protein

PNAS 108(47):18954-9

Harms MJ, Schlessman JL, Sue GR, García-Moreno E. B.
2010

Protein evolution by molecular tinkering: diversification of the nuclear receptor superfamily from a ligand-dependent ancestor

PLOS Biology 8(10):e1000497

Bridgham JT, Eick G, Larroux C, Deshpande K, Harms MJ, Gauthier MEA, Ortlund EA, Degnan BM, Thornton JW
2010

Analyzing protein structure and function using ancestral gene reconstruction

Current Opinions in Structural Biology 20(3):360-366

Harms MJ, Thornton JW
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

Harms MJ, Castañeda CA, Schlessman JL, Sue GR, Isom DG, Cannon BR, 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

Harms MJ, Schlessman JL, Chimenti MS, Sue GR, Damjanovic A, García-Moreno E. B.
2005

How sequence defines structure: a crystallographic map of DNA structure and conformation

PNAS 102(20):7157-7162

Hays FA, Teegarden A, Jones ZJR, Harms MJ, Raup D, Watson F, Cavaliere E, Ho PS
2003

Laser light-scattering evidence for an altered association of βB1-crystallin deamidated in the connecting peptide

Protein Science 13:678-686

Harms MJ, Wilmarth PA, Kapfer DM, Steel EA, David LL, Bachinger HP, Lampi KJ




Current Funding





Previous Funding





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