The Harms lab aims to understand the relationship between the biophysical properties of proteins and their evolution. How do the physical properties of proteins shape their evolutionary trajectories? Can we use evolutionary information to understand the mechanisms of modern proteins? To answer these (and other) questions, we combine biochemistry, biophysics, and evolutionary biology. We employ phylogenetics, 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.

Current projects:

• Evolution through sequence space. As proteins evolve, they traverse a "sequence space" of all possible amino acid sequences. We are using computational tools and high-throughput experiments to ask how the distribution of functional sequences in this space shapes protein evolution.
  
  • Sailer & Harms (2017) PNAS
  • Sailer & Harms (2017) PLoS Comp Bio
  • Sailer & Harms (2017) Genetics
  • Sailer & Harms (2018) bioRxiv preprint

• Evolution of innate immune proteins. The innate immune system is extraordinarily complicated, with multiple interacting protein and small-molecule signals. We are using an evolutionary approach to dissect the mechanism of the pro-inflammatory/antimicrobial molecule calprotectin and its interaction with Toll-like receptor 4.
  
  • Loes, Bridgham, Harms (2018) Frontiers in Immunology

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• Evolution of low-specificity proteins. S100 proteins are small, calcium binding proteins that bind to target proteins and regulate their functions in reponse to increased calcium concentration. Identifying the targets of these proteins has been challenging because they have very low specificity for their binding targets. We are using a combination of biochemical characterization and phylogenetics to attempt to identify the relevant targets.
  
  • Wheeler et al (2018) Biochemistry
  • Wheeler et al (2016) PLOS ONE
  • Wheeler & Harms (2017) BMC Biophysics

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• Open-source scientific software
  • pytc: software for advanced global fits of isothermal titration calorimetry data. (Duvvuri et al. (2018) Biochemistry)
  • epistasis: software for analysis of epistasis in genotype-phenotype maps. (Sailer & Harms (2017) Genetics)
  • Many more of our software packages are avaiable on github.

Check out the Harms lab website for more details