MCDB and CIRES/ Copley Lab Post-Doctoral Associate
The Copley lab in the Department of Molecular, Cellular and Developmental Biology and the Cooperative Institute for Research in Environmental Sciences is seeking a post-doctoral researcher to study the evolution of new enzymes and metabolic pathways.
Work in the Copley lab focuses on the evolutionary potential of promiscuous enzyme activities, the ubiquitous side activities of enzymes that normally serve other functions. Promiscuous activities can be recruited to serve new functions when a new enzyme enhances fitness. Further, multiple promiscuous enzymes can be patched together to form novel metabolic pathways. The evolution of new metabolic pathways by this mechanism has fueled metabolic innovation throughout the history of life on earth, and continues in the present day in response to the introduction of anthropogenic chemicals into the environment. However, our understanding of the process by which new metabolic pathways evolve is limited. We generally don’t know the genome of the organism in which a new pathway evolved and the details of the environment in which it lived. We can’t know the promiscuous activities that were available in its proteome, and we have only a few hints about the mutations that enabled assembly of an inefficient new pathway and subsequently improved its function.
The Copley lab uses experimental evolution to address these issues. We evolve microbes whose genome sequences are known under controlled environmental conditions. We identify mutations and determine how they improve fitness. We use biochemical, genetic and ‘omics techniques to address the impact of mutations from the molecular level to the system level.
Current projects in the lab address how the availability of different promiscuous activities in different microbes affects the evolution of new enzymes and pathways, the role of synonymous mutations in evolution, and the dynamics of gene duplication and divergence. The post-doctoral researcher will launch a new project aimed at understanding how the frequent “expedient” mutations that improve fitness under strong selective conditions at a cost to previously well-evolved functions can be avoided, compensated for, or repaired.
Morgenthaler, AB, Kinney, WR, Ebmeier, CC, Walsh, CM, Snyder, DJ, Cooper, VS, Old, WM and Copley, SD. “Mutations that improve the efficiency of a weak-link enzyme are rare compared to adaptive mutations elsewhere in the genome”. eLife 8:e53535, 2019. PMID: 31815667
Kim, J, Flood, JJ, Kristofich, M, Gidfar, C, Morgenthaler, AB, Fuhrer, T, Sauer, U, Snyder, D, Cooper, VS, Ebmeier, CC, Old, WM, and Copley, SD. “Hidden resources in the E. coli genome restore PLP synthesis and robust growth after deletion of the “essential” gene pdxB”, PNAS 116 (48), 24164-24173, 2019. PMID 31712440
Kristofich, J-C, Morgenthaler, AB, Kinney, WR, Snyder, DJ, Ebmeier, CC, Old, WM, Cooper, VS, and Copley, SD. “Synonymous mutations make dramatic contributions to fitness when growth is limited by a weak-link enzyme”, PLoS Genetics, 14, e1007615, 2018. PMID 30148850
Qualifications include a recent Ph.D. in biochemistry, molecular biology, or microbiology. Experience with high-throughput sequencing, microbial genetics and/or enzymology is desirable. The successful applicant will have a strong work ethic, excellent communication and organization skills, and a willingness to learn new methodologies.
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