Our lab works on questions at the intersection of physiology and evolutionary biology, and we integrate systems-level, mathematical models to generate quantitative predictions that linking genotype to phenotype. Nearly all of our work has refocused upon using Methylobacterium extorquens as a model system.

The laboratory currently tackles the following areas:

(1.) Exploring a novel stress response that directly links accumulation of the toxic intermediate formaldehyde to translational inhibition. This project ranges from structure-function analysis of the regulatory protein, EfgA, to unexpected population heterogeneity in the ability to handle formaldehyde stress.

(2.) Using in vivo gene editing, deep-sequencing, and kinetic models to uncover the epistatic interactions that constrain evolvability or biotechnological applications of synthetic metabolic pathways.

(3.) Predicting microbial interactions within synthetic, plant-associated communities. This includes the role of methylotrophs in aiding in the demethoxylation of lignin monomers and interactions between Methylobacterium strains.

Funding Resources:

• 2017-2020       National Science Foundation: “Collaborative Research: Deep-sequencing analysis of edited metabolic pathways to uncover, model, and overcome epistatic constraints upon optimization” (other PIs: Jeremy A. Draghi, CUNY Brooklyn College; N. Cecilia Martinez-Gomez, Michigan State; co-PIs: Sergey Stolyar, Ankur B. Dalia, Indiana U.; MCB-1714949)

 

• 2017-2018       BEACON NSF Center for the Study of Evolution in Action: “Off the deep end of the gene pool: deep-sequencing and metabolomics analysis as a framework for uncovering fitness landscapes and modeling evolvability in engineered metabolic networks” (PI: Eric L. Bruger; other co-PIs: Sergey Stolyar, N. Cecilia Martinez-Gomez, Michigan State)

 

• 2017-2018       BEACON NSF Center for the Study of Evolution in Action: “It only gets worse from here: adaptation in the face of ever-larger pulses of stress” (PI: Jannell V. Bazurto; other co-PIs: Benjamin Kerr, Sonia Singhal, U. Washington; Emily Dolson, Michigan State)

 

• 2014-2017       Department of Energy: “A high-throughput pipeline for mapping inter-species interactions and metabolic synergy relevant to next-generation biofuel production” (PI: Daniel Segrè, Boston U.; other co-PI: Trent R. Northen, LBNL; DE-SC0012627)

 

• 2012-2018       Department of Defense, Army Research Office: “Associating growth conditions with cellular composition in Gram-negative bacteria” (PI: Claus Wilke, U. Texas, Austin; other co-PIs: Ioannis C. Paschalidis, Daniel Segrè, Boston U.; M. Stephen Trent, U. Georgia; Jeffrey E. Barrick, Edward M. Marcotte, Pradeep Ravikumar, U. Texas, Austin; W911NF-12-1-0390)

 

•  2016-2017       BEACON NSF Center for the Study of Evolution in Action: “What does the flux say: Empirical validation of flux balance analysis” (PI: Luis Zaman, U. Washington; other co-PIs: Benjamin Kerr, U. Washington; Richard E. Lenski, Michigan State)

 

• 2015-2016       NIH-funded Center for Modeling Complex Interactions: “Pilot Grant: Modeling variability in persistence induced from within by a toxic metabolite” (co-PI: Andreas E. Vasdekis; collaborator: Christopher H. Remien)

 

• 2014-2015       BEACON NSF Center for the Study of Evolution in Action: “Mechanistic basis of mutations potentiating the evolution of citrate utilization in the LTEE” (PI: Jeffrey E. Barrick, U. Texas, Austin; other co-PI: Zachary D. Blount, Michigan State)

 

• 2011-2014       Department of Energy: “Modeling, patterning and evolving syntrophic communities that link fermentation to metal reduction” (co-PIs: Nathaniel C. Cady, U. Albany; Colleen M. Hansel, WHOI; Daniel Segrè, Boston U.; DE-SC0006731)

 

• 2011-2014       Department of Energy: “Modeling, patterning and evolving syntrophic communities that link fermentation to metal reduction” (co-PIs: Nathaniel C. Cady, U. Albany; Colleen M. Hansel, WHOI; Daniel Segrè, Boston U.; DE-SC0006731)

 

• 2010-2013       National Science Foundation: “Hopanoid physiology: implications for microbial life on the early earth” (co-PI: Ann Pearson, Harvard, EAR-1024723)

 

• 2010-2013       Department of Energy: “An open source platform for multi-scale spatially distributed simulations of microbial ecosystems” (PI: Daniel Segrè, Boston U.; other co-PI: Nathaniel C. Cady, U. Albany; DE-SC0004962)

 

• 2009-2014       National Science Foundation: “CAREER: Distribution of Fitness Effects, Identity and Interaction of Beneficial Mutations Available for Adaption.” (DEB-0845893)

 

• 2009-2011       National Institutes of Health: ARRA Supplement to “Systems-level physiological basis of selection and epistasis in adaptation.” (3R01 GM078209-03S1)

 

• 2007-2013       National Institutes of Health: “Systems-level physiological basis of selection and epistasis in adaptation.” (co-PI: Daniel Segrè, Boston U., 1R01 GM078209-01A1)

 

• 2006-2007       The Clark/Cooke Fund: “Evolution of metabolic specialization and tradeoffs in laboratory populations.”

 

• 2006-2007       National Science Foundation: Microbial Biology Special Starter Grant: “Adaptation, tradeoffs and specialized metabolism in experimental and natural populations.” (IOB-0612591)

 

• 2006                The William F. Milton Fund: “Influence of environmental factors on the emergence of cooperation and coevolution in defined, multi-species microbial consortia.”