Sauer Lab, Relating stochastic fluctuations of metabolic gene regulation to antibiotic tolerance

Stochasticity inherent in biochemical processes, such as fluctuations in gene expression levels, can determine bacterial cell fates when exposed to antibiotics. Previous work in the lab on a population level has found specific functional roles of bacterial metabolism in mediating the immediate response to antimicrobial treatments. In particular, we found experimental evidences relating central carbon metabolism and the production of a nucleotide sugar to the immediate response of E.coli to protein synthesis (i.e. macrolides) and gyrase inhibitors (i.e. quinolones), respectively. Whether and how heterogeneity in the expression of enzymes within these metabolic pathways can affect the tolerance to these classes of antibiotics is unclear.

The goal of this project is to use quantitative single-cell time-lapse microscopy and imaging analysis to study heterogeneous cell behavior in response to antibiotic exposure. We aim at investigating whether cell to cell variations in the expression of genes related to the aforementioned metabolic processes can be responsible for the emergence of subpopulation of antibiotic-tolerant bacteria.

The candidate will familiarize with microscopy techniques, microbial cultivation and image processing to interpret and analyze the time lapse datasets. Basic experience in programming (Matlab) is required.

Contact: Mattia Zampieri