Chubiz Lab

The Chubiz Lab at UMSL

What We Do

We use genetic and biochemical approaches to understand how novel regulatory and metabolic pathways evolve and shape bacterial physiology. With this perspective, we look to address questions in bacterial drug resistance, pathogenesis, biogeochemistry, and microbial ecology.

Evolution of the mar-sox-rob resistance regulon

The intrinsic levels of drug resistance found in numerous bacterial pathogens has interested my research group for several years. Specifically, we focus on drug resistance mechanisms that are not associated with acquired plasmids, phages, transposon, integrons, and the like. Major questions we examine in this area are:

  • How do bacteria sense and respond to antibiotic stress?
  • How are different cellular responses integrated to allow bacteria to acclimate to antibiotic stress?
  • How are various independent aspects of cellular physiology and metabolism dynamically controlled to increase tolerance to intracellular chemical stress?
  • How have these mechanisms evolved throughout closely related bacterial species?

A model system for studying these questions is the mar-sox-rob system found in E. coli and closely related enterobacterial pathogens. With regards to this system, I have previously explored the transcriptional inter-connections between its members, its role in outer membrane permeability, and how intracellular metabolites act as inducers of intrinsic resistance.

Recently, we have discovered that the mar-sox-rob regulon of Salmonella is integrated into the complex network of environmental sensing and signal transduction that controls expression of virulence traits. In part, we have found regulation virulence traits occurs through repression of flagellar gene expression. This functionality is divergent from mar-sox-rob regulatory patterns found in E. coli, demonstrated the evolutionary plasticity of the mar-sox-rob regulon.

This work is generously supported by the National Institute of Allergy and Infectious Diseases (AI137984). Graduate funding is available for Ph.D. students. Contact us.

Genetic robustness of microbe-microbe interactions

Given the myriad of microbes co-existing in nearly all environments on Earth, we have a limited picture of how microbes function in the context of a community. In particular, how sensitive are microbial relationships to loss-of-function or gain-of-function mutatations? Does the poly-microbial environment select for genetic robustness? We try and explore these questions using model systems of bacterial cooperation and antagonism. For instance, in a recent study, in collaboration with Will Harcombe (U of MN), we found that different types of interactions (cooperation, unidirectional crossfeeding, and competition) result in different patterns of sensitivity to metabolic loss-of-function. Interestingly, competition appears to be most senstitive to loss-of-function, despite the perceived delicacy of mutualistic behavior.

In more recent work, we have been exploring how antagonism between closely related bacteria shapes the outcomes of simple ecological networks. Here, we look to understand the degree to which pair-wise interactions can predict assembly outcomes of ecological networks with varying degrees of connectedness.

Emergence and evolutionary refinement of novel metabolic pathways

How easily can novel metabolic pathways emerge in Bacteria? Many free living bacteria have diverse catabolic metabolisms, yet have restricted diets. One example is the respiratory generalist Shewanella oneidensis whose carbon diet is largely restricted to organic acids (i.e. it does not eat glucose) despite having the metabolic capacity to consume carbohyrdates. Despite this limitation in nature, S. oneidensis rapidly evolves to consume glucose under laboratory conditions. We have undercovered the genetic basis for this novel metabolism and its associated trade-offs.. Subsequently, we have experimentally evolved these glucose-eating S. oneidensis for over 600 generations on a glucose-only diet. We have observed more than 2-fold increases in relative fitness. We are currently correlating causative mutations to effects on central carbon metabolism.

Physiology and molecular genetics of Acidobacteria

What are the keys to the ecological success of Acidobacteria? Acidobacteria are ubiquitous and abundant in soil environments, yet we know very litte about them. In large part, this is due to the difficulty in isolating and cultivating these bacteria under laboratory conditions. One path towards understanding this phylum and the their ecological role in soils is to study culturable species. My lab is currently engaged in an effort to develop genetic tools to study the physiology and metabolism of these soil dwelling microbes. Likewise, we are actively sequencing numerous Acidobacteria genomes in an effort to understand the genetic and catabolic diversity of the Acidobacteria phylum.

These efforts support another goal of understanding how these Acidobacteria produce a unique class of membrane-spanning lipids known as branched dialkyl glycerol tetraether lipids (brGDGT). These lipids are a bacterial analog to the biphytanyl lipids found in some Archaea, and have emerged as a geochemical paleoclimate proxy. We have used a shotgun lipidomics approach to understand how environmental factors shape the abundance and structure of these lipids in a model Acidobacteria. This work will help refine the use of brGDGT in paleoclimate modeling.

Are you interested in the Chubiz Lab?

Contact us about opportunities! We are always excited to hear from motivated prospective undergraduate, Ph.D., and post-doctoral researchers.

Current Lab Members

  • Lon Chubiz, Ph.D. - Principal Investigator
  • Silpi Thota - Ph.D. 2019 / Post-doctoral Researcher
  • Yu Liu - Post-doctoral Researcher
  • Sage Rohrer - Ph.D. Student (NSF GRFP Fellow), co-advised with Dr. Patricia Parker
  • Danish Gul - Ph.D. Student
  • Heather Sexton - M.S. Student
  • Elisabeth Day - Undergraduate
  • Brittany Henry - Undergraduate
  • Coryn Cenzer - Undergraduate
  • Alex King - Undergraduate

Former Lab Members

  • Marisa Yoder, M.S. 2018 - Donald Danforth Plant Science Center
  • Venkata Jonnalagadda, M.S. 2017 - Sr. Biological Scientist, University of South Florida
  • Safia Madani, M.S. 2016 - Biomerieux
  • Victoria Anderson, M.S. 2016 - MilliporeSigma

Interested students and post-doctoral researchers

I am always keen to provide opportunities for students at the graduate and undergraduate levels. If you are interested in my research program, and would like training microbiology, molecular biology, and microbial evolution please contact me.

For students interested in performing their Ph.D. graduate work in my lab, please refer to graduate admissions policies found on the Department of Biology website. Students entering into the Cellular and Molecular Biology track wil be expected to perform laboratory rotations as part of the degree program - my lab is always open to rotators. Those entering the Evolution, Ecology and Systematics track must contact me prior to applying for me to confirm your application. I look forward to hearing from you.

For post-doctoral researchers, space is available but I currently do not have funding for a post-doc position. However, I am always eager to see what can be worked out so please reach out and contact me if you are interested.

Publications

At UMSL

  • McClelland, H.L.O., Jones, C., Chubiz, L.M., Fike, D.A., and Bradley, A.S., Direct Observation of the Dynamics of Single-Cell Metabolic Activity During Microbial Diauxic Growth, mBio, 2020
  • Thota, S.S. and Chubiz, L.M. 1, Multidrug resistance regulators MarA, SoxS, Rob, and RamA repress flagellar gene expression and motility in Salmonella enterica Serovar Typhimurium, J Bacteriol, 2019
  • Harcombe, W.R., Chacon, J.M., Adamowicz, E.M., Chubiz, L.M., and Marx, C.J., Evolution of bidirectional costly mutualism from byproduct consumption, PNAS, 2018
  • Douglas, S.M., Chubiz, L.M., Harcombe, W.R., and Marx, C.J., Identification of the potentiating mutations and synergistic epistasis that enabled the evolution of inter-species cooperation, PLoS One, 2017
  • Chubiz, L.M. 1 and Marx, C.J., Growth tradeoffs accompany the emergence of glycolytic metabolism in Shewanella oneidensis MR-1, J. Bacteriol., 2017
  • Douglas, S.M., Chubiz, L.M., Harcombe, W.R., Ytreberg, F.M., and Marx, C.J., Parallel Mutations Result in a Wide Range of Cooperation and Community Consequences in a Two-Species Bacterial Consortium, PLoS One, 2016
  • Agashe, D., Sane, M., Phalnikar, K., Diwan, G.D., Habibullah, A., Martinez-Gomez, N.C., Sahasrabuddhe, V., Polachek, W., Wang, J., Chubiz, L.M., and Marx, C.J., Large-Effect Beneficial Synonymous Mutations Mediate Rapid and Parallel Adaptation in a Bacterium, Mol. Biol. Evol., 2016
  • Chubiz, L.M. 1, Granger, B.R., Segrè, D., and Harcombe, W.R., Species interactions differ in their genetic robustness, Front Microbiol, 2015
  • Carroll, S.M., Chubiz, L.M., Agashe, D., and Marx C.J., Parallel and Divergent Evolutionary Solutions for the Optimization of an Engineered Central Metabolism in Methylobacterium extorquens AM1, Microorganisms, 2015

Elsewhere

  • Chubiz, L.M., Purswani, J., Carroll, S.M., and Marx, C.J., A novel pair of inducible expression vectors for use in Methylobacterium extorquens, BMC Res Notes, 2014
  • Chubiz, L.M., Lee, M.C., Delaney, N.F., and Marx, C.J., FREQ-Seq: a rapid, cost-effective, sequencing-based method to determine allele frequencies directly from mixed populations, PLoS One, 2012
  • Chubiz, L.M., Glekas, G.D., and Rao, C.V., Transcriptional cross talk within the mar-sox-rob regulon in Escherichia coli is limited to the rob and marRAB operons, J Bacteriol, 2012
  • Chubiz, L.M. and Rao, C.V., Role of the mar-sox-rob regulon in regulating outer membrane porin expression, J Bacteriol, 2011
  • Chubiz, L.M. and Rao, C.V., Aromatic acid metabolites of Escherichia coli K-12 can induce the marRAB operon., J Bacteriol, 2010
  • Min, T.L., Mears, P.J., Chubiz, L.M., Rao, C.V., Golding, I., Chemla, Y.R., High-resolution, long-term characterization of bacterial motility using optical tweezers, Nat Methods, 2009
  • Chubiz, L.M. and Rao, C.V., Computational design of orthogonal ribosomes, Nucleic Acids Res, 2008
  1. Indicates corresponding author  2 3