My lab studies the mechanisms by which protein functions evolve. We do this by phylogenetically reconstructing the histories of ancient proteins and then synthesizing, manipulating, and experimentally characterizing their biological functions and physical properties.
This kind of work is powerful and fun — and possible at all — because we are a diverse group of evolutionary biologists, biochemists, biophysicists, computational biologists, geneticists, and molecular biologists, all working together and freely mingling our expertise, techniques, and ideas.
We address classical and recent questions about the nature of evolutionary processes, such as: How do complex molecular systems evolve? Does evolution proceed by a few large-effect or many small-effect mutations? Does epistasis shape the evolutionary process and make the pathways and outcomes of evolution contingent on chance events? Is evolution reversible? How does the architecture of biological systems shape the evolutionary process? How did evolution produce those architectures in the first place?
Evolutionary analysis can also help address core questions in biochemistry, biophysics, and molecular biology. Why do proteins have the particular architectures that they do? How does that architecture itself evolve? What structural and genetic mechanisms cause functions to differ between members of protein families? How do molecular machines, allostery, and molecular interfaces evolve? Are proteins’ physical properties always optimized for their functions, and if not, why not? Can history explain why particular proteins are subject to interference by particular drugs and pollutants? We have found that detailed reconstruction of proteins’ histories helps us to understand why and how their present-day descendants work as they do today.
Columbia University/ American Museum of Natural History
Ph.D - Biological Sciences
The simplicity of protein sequence-function relationships.
The simplicity of protein sequence-function relationships. bioRxiv. 2023 Sep 05.
Evolutionary Shortcuts via Multinucleotide Substitutions and Their Impact on Natural Selection Analyses.
Evolutionary Shortcuts via Multinucleotide Substitutions and Their Impact on Natural Selection Analyses. Mol Biol Evol. 2023 07 05; 40(7).
Simple mechanisms for the evolution of protein complexity.
Simple mechanisms for the evolution of protein complexity. Protein Sci. 2022 11; 31(11):e4449.
Epistatic drift causes gradual decay of predictability in protein evolution.
Epistatic drift causes gradual decay of predictability in protein evolution. Science. 2022 05 20; 376(6595):823-830.
Molecular and structural basis of olfactory sensory neuron axon coalescence by Kirrel receptors.
Molecular and structural basis of olfactory sensory neuron axon coalescence by Kirrel receptors. Cell Rep. 2021 11 02; 37(5):109940.
Contingency and chance erase necessity in the experimental evolution of ancestral proteins.
Contingency and chance erase necessity in the experimental evolution of ancestral proteins. Elife. 2021 06 01; 10.
A hydrophobic ratchet entrenches molecular complexes.
A hydrophobic ratchet entrenches molecular complexes. Nature. 2020 12; 588(7838):503-508.
Comment on "Ancient origins of allosteric activation in a Ser-Thr kinase".
Comment on "Ancient origins of allosteric activation in a Ser-Thr kinase". Science. 2020 11 20; 370(6519).
Author Correction: Origin of complexity in haemoglobin evolution.
Author Correction: Origin of complexity in haemoglobin evolution. Nature. 2020 Jul; 583(7816):E26.
Origin of complexity in haemoglobin evolution.
Origin of complexity in haemoglobin evolution. Nature. 2020 05; 581(7809):480-485.
Steenbock Distinguished Lecturer in Biochemistry
University of Wisconsin
Distinguished Alumni Lectureship
University of Queensland School of Biochemistry
Guggenheim Foundation Fellowship
Hans Falk Award
National Institute for Environmental Health Sciences
Richard Jones Investigator Award
Oregon Medical Research Foundation
Early Career Investigator
Howard Hughes Medical Institute
U.S. Presidential Early Career Award for Scientists and Engineers
Alfred P. Sloan Foundation Research Fellow
National Science Foundation
Distinguished University Lecturer in Environmental Sustainability