Large-scale efforts in genome sequencing have elucidated much of the "parts list" for thousands of species, but a general description of how genes collectively interact to produce functioning systems eludes us. We use statistical analysis of genome sequences drawn from thousands of organisms to distill out general patterns describing the organization of cellular systems. These statistical models are then tested for their ability to explain, predict, and design cellular behaviors in the lab. In recent work, we have used statistical sequence analysis to re-wire kinase signalling pathways, and to understand genetic interactions in folate metabolism. We are particularly interested in the idea that cellular systems might be decomposed into simpler, modular building blocks.
Kim is a Moore Investigator in Data-Driven Discovery. She completed a PhD in biophysics at UC Berkeley with Dr. Tracy Handel, where she studied the computational design of protein-protein interfaces. As a postdoctoral researcher, she developed a model for the evolution of new allosteric regulation and experimentally tested the idea of allosteric "hot spots" with Dr. Rama Ranganathan (at UT Southwestern).
- evolution and engineering of cellular systems
- protein regulation and inter-protein communication
- statistical analysis of genomes and prediction of functional interactions
- Structurally distributed surface sites tune allosteric regulation.
- McCormick JW, Russo MAX, Thompson S, Blevins A, Reynolds KA BioRxiv 2021
- A simplified strategy for titrating gene expression reveals new relationships between genotype, environment, and bacterial growth.
- Mathis AD, Otto RM, Reynolds KA, Nucleic Acids Res 2020 Nov
- Altered expression of a quality control protease in E. coli reshapes the in vivo mutational landscape of a model enzyme.
- Thompson S, Zhang Y, Ingle C, Reynolds KA, Kortemme T, Elife 2020 07 9
- A Two-Enzyme Adaptive Unit within Bacterial Folate Metabolism.
- Schober AF, Mathis AD, Ingle C, Park JO, Chen L, Rabinowitz JD, Junier I, Rivoire O, Reynolds KA, Cell Rep 2019 Jun 27 11 3359-3370.e7
- Engineering allosteric regulation in protein kinases.
- Pincus D, Pandey JP, Feder ZA, Creixell P, Resnekov O, Reynolds KA Sci Signal 2018 Nov 11 555
- High-Order Epistasis in Catalytic Power of Dihydrofolate Reductase Gives Rise to a Rugged Fitness Landscape in the Presence of Trimethoprim Selection.
- Tamer YT, Gaszek IK, Abdizadeh H, Batur TA, Reynolds KA, Atilgan AR, Atilgan C, Toprak E, Mol. Biol. Evol. 2019 Jul 36 7 1533-1550
- An evolution-based strategy for engineering allosteric regulation.
- Pincus D, Resnekov O, Reynolds KA Phys Biol 2017 Apr 14 2 025002
- Evolution-Based Functional Decomposition of Proteins.
- Rivoire O, Reynolds KA, Ranganathan R PLoS Comput. Biol. 2016 Jun 12 6 e1004817
- Hot spots for allosteric regulation on protein surfaces.
- Reynolds KA, McLaughlin RN, Ranganathan R Cell 2011 Dec 147 7 1564-75