# Evolution and Regulation of Bacterial Proteome Composition

> **NIH NIH R35** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2024 · $468,870

## Abstract

Project Summary/Abstract
The proteome is a quantitative output of a genome and the ultimate effector of cellular functions. Yet
remarkably little is known about the logic behind proteome construction. The goal of my research program is to
understand the evolutionary driving forces and the molecular processes that shape protein levels in living cells.
Using bacterial model systems, my lab takes a holistic approach by developing quantitative technologies to
measure, manipulate, and model the expression stoichiometry of co-regulated proteins and the effect of
imbalanced production on bacterial growth, survival, and colonization. This current grant seeks to answer
several fundamental questions regarding the physiology and regulation of protein stoichiometry.
 At the physiological level, we use molecular and theoretical methods to determine 1) the optimality of
protein production rates for every gene and the cellular responses to non-optimal levels, 2) the precise ratios of
protein production upon sudden environmental changes and the consequences of imbalanced production, and
3) the theoretical basis for the stoichiometry of proteins that function together. These studies will help elucidate
new principles for building a proteome and provide a new way of thinking about protein imbalance in disease.
 To understand the regulatory principles of gene expression behind this stoichiometric protein production,
we use quantitative and massively parallel assays to determine 1) the sequence determinant of Rho-
dependent transcription termination in Bacillus subtilis, whose RNAP polymerases outpace ribosomes
(`runaway transcription'), 2) the molecular basis of runaway transcription, 3) a predictive model for the
efficiency of Rho-independent transcription termination, and 4) the landscape of translational control for
bacteriophage mRNAs. Our studies in these areas will help establish a critically needed framework for
predicting gene expression from genomic sequences and advance fundamental knowledge of bacterial gene
regulation. We anticipate that our mechanistic dissection, coupled with systems-level inquiry into proteome
composition, will make bacterial model organisms the first system for which we have a quantitative
understanding of the interplay between genome, proteome, and fitness.

## Key facts

- **NIH application ID:** 10771160
- **Project number:** 5R35GM124732-07
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Gene-Wei Li
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $468,870
- **Award type:** 5
- **Project period:** 2017-09-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10771160

## Citation

> US National Institutes of Health, RePORTER application 10771160, Evolution and Regulation of Bacterial Proteome Composition (5R35GM124732-07). Retrieved via AI Analytics 2026-09-07 from https://api.ai-analytics.org/grant/nih/10771160. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*