Gene-Wei Li, Ph.D.

Research

How DNA encodes precise levels of protein output is a major unsolved problem in genome science and technology. Our studies revealed remarkable precision in gene expression, as nearly all components of protein complexes are synthesized at ratios matching their structural stoichiometry, and failure to do so can cause severe dysfunction. In contrast to this biological precision, we are far from being able to decode protein synthesis rates based on genome sequences, even in single-cell organisms. My laboratory is solving this problem in bacteria with several long-term visions: (i) create a field of predictive protein synthesis, leveraging bacteria as a testbed to establish generally applicable rules and tools; (ii) define the molecular basis of every central-dogma process in bacteria, providing conserved guiding principles for higher organisms; and (iii) enable deeper understandings of microbial gene regulation—an inseparable part of human physiology, diseases, and the environment.

As an Innovation Fund investigator, Gene-Wei Li, Ph.D., is teaming up with Katsuhiko Murakami, Ph.D., to study a critical step of gene regulation in a distinct group of bacteria known as cyanobacteria. Proper expression of genes is critical for the health of all organisms. One key step in this process is known as transcription termination, meaning the way in which RNA polymerase stops making RNA based on where a gene ends within a DNA sequence. Cyanobacteria play a critical role in everyday life: They are responsible for the majority of carbon fixation on Earth but also cause illness in humans and livestock. Surprisingly, the molecular mechanism by which transcription termination occurs in cyanobacteria is unknown, despite this process being well documented in other model bacteria. The collaboration will combine Murakami’s expertise in structural biology of RNA polymerase with Li’s knowledge of transcriptional regulation to establish a new model for microbial transcriptional termination in cyanobacteria. Their discoveries could have broad-reaching impacts extending to chloroplasts and other bacterial species.