Understanding the Forces that Shape Bacterial Proteomes
Inside a living cell is a crowded space filled with thousands of different proteins. The levels among these proteins are far from uniform ”“ their production rates must be tuned to meet cellular demands. My lab seeks to understand quantitatively (i) how bacteria fine-tune mRNA and protein levels and (ii) what defines the demand for absolute protein levels. We address these questions by adapting new technologies for genome-wide quantitation of protein synthesis rates, high-resolution mapping of post-transcriptional RNA processing sites, and high-throughput genetic perturbation and phenotyping. Our goal is to elucidate principles for setting absolute protein levels and proteome composition.
The cellular demand for protein functions may not only exert on the expression of a single gene, but also a group of genes whose products share functional redundancy or overlap. Backup circuits can be advantageous for protecting bacteria from internal fluctuations in protein levels and external insults such as antibiotics. However, identifying functional backups and overlaps in bacteria has proven difficult. To overcome this challenge, we are developing new strategies to systematically discover genes with overlapping functions by exploiting their regulatory capacities. We anticipate that new principles of gene regulation and deeper understandings of bacterial physiology will likely emerge from this study.