Wenhan Zhu, Ph.D.

Research

Life emerged in an oxygen-free world where anaerobic bacteria flourished. Even today, many of the descendants of these earliest microbes continue to thrive in oxygen-free habitats. However, exposure to oxygen can be harmful or even fatal for these microorganisms. The human large intestine, which normally lacks oxygen, is home to trillions of beneficial anaerobic bacteria. However, inflammatory conditions are associated with increased oxygen levels, causing a decline in the population of beneficial gut bacteria while promoting the growth of microbial species that worsen inflammation and diseases. To tackle this issue, the Zhu lab will utilize advanced techniques in microbial genetics, biochemistry, and metabolic engineering to enhance oxygen tolerance of an oxygen-sensitive intestinal microbe. By limiting the internal production of toxic oxygen molecules and by identifying and replacing its vulnerable enzymes with oxygen-tolerant equivalents, the lab aims to identify the metabolic processes that underlie anaerobic bacteria’s inability to survive in oxygen-rich environments. These modified bacteria will then be introduced into animals with intestinal inflammation to assess the bacteria’s potential to improve commensal resilience and gut inflammation. Through this work, the lab hopes not only to address the question of why anaerobic bacteria cannot survive oxygen exposure but also to pave the way for leveraging bacterial physiology to ameliorate inflammatory disease.