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 link genotype to phenotype. Nearly all of our work has focused upon using Methylorubrum extorquens (formerly Methylobacterium) as a model system.

The laboratory currently tackles the following areas:

(1.) Phenotypic heterogeneity and epigenetic memory in stress tolerance using formaldehyde tolerance between genetically-identical cells as our model system. This stretches from understanding the physiological underpinnings that distinguish individual cells to exploring the entanglement that can occur when both Lamarckian and Darwinian evolution proceed concurrently.

(2.) Developing M. extorquens as a platform for conversion of lignin-derived methoxylated aromatics into butanol. This ties together novel findings of the role of formaldehyde toxicity in using methoxylated compounds to the discovery that growth, survival, nutrient acquisition, and production are all highly variable at the single-cell level.

(3.) Roles of phylogeny, genome content, and functional performance traits in the evolution and assembly of the diverse plant-associated Methylobacterium/Methylorubrum community. This work combines genomic analyses of the genus with high-throughput phenotyping and tracking of ecological assembly.

(4.) 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. This project leverages strains engineered to utilize novel pathways and has led, yet again, to surprising discoveries related to phenotypic heterogeneity in growth stability.

Funding Resources:

• 2021-2024      Department of Energy: “Converting methoxy groups on lignin-derived aromatics from a toxic hurdle to a useful resource: a systems-driven approach” (Co-PIs: Andreas E. Vasdekis; N. Cecilia Martinez-Gomez, UC Berkeley; Jeremy A. Draghi, Virginia Tech; award in process)

• 2018-2022       National Science Foundation: “Dimensions: An inordinate fondness for Methylobacterium– roles of phylogeny, genome content, and functional performance traits in the evolution and assembly of a diverse plant-associated community” (Co-PIs: James A. Foster, John M. (Jack) Sullivan; N. Cecilia Martinez-Gomez, UC Berkeley; Jessica A. Lee, Global Viral; Collaborators: Sergey Stolyar; Steven W. Kembel, B. Jesse Shapiro, U. Québec, Montréal, Canada; DEB-1831838).

• • • • 2018-2022       Department of Energy: “Using gene editing and an accumulated bioproduct as a reporter for genotypic to phenotypic heterogeneity in growth-vs-production for Methylobacterium extorquens conversion of lignin-derived aromatics to butanol” (Co-PIs: Sergey Stolyar, Andreas E. Vasdekis; Ankur B. Dalia, Indiana U.; DE-SC0019436).

• 2017-2022       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, Virginia Tech; N. Cecilia Martinez-Gomez, UC Berkeley; co-PIs: Sergey Stolyar, Ankur B. Dalia, Indiana U.; MCB-1714949)

• 2017-2021       National Science Foundation (EPSCoR): “RII Track-2 FEC: Using biophysical protein models to map genetic variation to phenotypes” (PI: Frederick M. Ytreberg; co-PIs Craig R. Miller; Brandon Ogbunugafor, was at U. Vermont now Yale; Daniel M. Weinreich, Brown; OIA-1736253).