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Gene-Wei Li, Ph.D.

Department of Biology
Assistant Professor

Room 68-223A
(617) 324-46703 (phone)

Biosketch

Ph.D. Physics, Harvard University, 2010

Research Summary

Our laboratory aims to elucidate how cells optimize their genetic information to establish desired physiology. We use ‘simple’ bacterial cells to discover quantitative principles governing gene expression. Our approach is to invent new tools that provide key missing observables, coupled with the development of analytical frameworks enabled by these new observables. Ultimately, we want to understand how cells work as an optimization process through evolution. We are currently focusing on answering these two questions:

How do cells fine-tune protein synthesis rates? Our recent work revealed that bacteria have evolved to set the production rate of a protein to a desired level with small errors. This remarkable precision sharply contrasts with the current technological bottleneck in quantitatively controlling protein synthesis in bacteria. Our lab is developing several high-resolution methods to define the post-transcriptional processes that determine the rates of protein synthesis. Our goal is to understand how biological systems are set up to achieve high precision, which will help advance studies in both basic and synthetic biology.

What determines the optimal protein level? Cells tightly regulate their protein expression, but we have no means of rationalizing the observed levels for most proteins. Traditional studies of cellular pathways and processes have largely omitted information on absolute protein abundance, even though it is one of the key outcomes of gene regulation. Our lab is developing theoretical and experimental frameworks for understanding the balancing act between the need for protein activity and the cost of protein synthesis, with an initial focus on amino acid biosynthetic enzymes. From a systems perspective, we are also trying to determine the extent to which genetic regulatory networks have evolved to buffer against fluctuations in protein levels. Our goal is to provide a conceptual framework for rationalizing the quantitative composition of a proteome that is shaped by evolution.

Selected Publications

  • Li GW, Burkhardt D, Gross CA, Weissman JS. Quantifying Absolute Protein Synthesis Rates Reveals Principles Underlying Allocation of Cellular Resources. Cell  157: 624 (2014).
  • Li GW, Oh E, Weissman JS. The anti-Shine-Dalgarno sequence drives translational pausing and codon choice in bacteria. Nature  484: 538 (2012).
  • Wang W*, Li GW*, Chen C*, Xie XS, Zhuang X. Chromosome organization by a nucleoid-associated protein in live bacteria. Science  333: 1445 (2011). *equal contribution
  • Li GW, Xie XS. Central dogma at the single-molecule level in living cells Nature  475: 308 (2011).
  • Taniguchi Y*, Choi PJ*, Li GW*, Chen H* et al. Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells. Science  329: 533 (2010). *equal contribution
  • Li GW, Berg OG, Elf J. Effects of macromolecular crowding and DNA looping on gene regulation kinetics. Nature Physics  5: 294 (2009).
  • Elf J*, Li GW*, Xie XS. Probing transcription factor dynamics at the single-molecule level in a living cell. Science 316: 1191 (2007). *equal contribution

Last Updated: December 20, 2015