Thanks to a prestigious national award, a researcher at UW-Madison will have a chance to learn exactly how cells protect themselves from pathogens that invade the cytosol, the watery fluid in which organelles live inside the cell.

These studies could have a profound impact on treating bacterial illnesses, according to JD Sauer, PhD, assistant professor of medical microbiology and immunology at the UW School of Medicine and Public Health.

For his ideas, Sauer received the 2018 Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease award.

The cytosol contains the organelles including the nucleus, where DNA is stored and genes are expressed; the endoplasmic reticulum, where proteins are made; and the mitochondria, where energy is generated. 

Some disease-causing bacteria like Listeria monocytogenes, which is contracted through tainted food, bypass normal barriers to infection and enter the cytosol where they replicate and ultimately cause disease. Sauer’s lab will use award funds to understand how cells fight off bacteria in cytosol.

The $500,000 Burroughs Wellcome Fund award, which will help support Sauer’s work for the next five years, provides the pilot funding to allow him to pursue this new line of research using novel cutting-edge approaches.

“Although these studies will complement the other core components of our lab where we study tumor immunotherapy and bacterial pathogenesis and antibiotic development, this work is unique and separate from these core components of the lab and will provide the groundwork for a whole new direction of study, not only for my lab, but for the field as a whole,” he said.

Sauer’s work will use two parallel approaches to examine how cells interact with bacteria in their cytosol.

His team will use gene-editing technology called CRISPR/Cas9 to identify genes that program defenses in the cytosol to kill invading pathogens. In parallel, they will use cutting-edge technology to understand how cells change both their metabolism and what genes they express when they are infected by bacteria.

“Ultimately, the results of these studies can be used to inform the design of novel treatments that activate our cells’ natural defenses, or to subvert the bacterial adaptations that avoid these defenses,” he said.

The Burroughs Wellcome Fund, based in Research Triangle Park, North Carolina, is a private foundation that supports biomedical research and other scientific and educational activities, according to its website. The Burroughs Wellcome Fund has two primary goals: to help scientists early in their careers develop as independent investigators, and to advance fields in the basic biomedical sciences that are undervalued or in need of particular encouragement.

Its financial support is channeled primarily through competitive peer-reviewed award programs. Grants are given primarily to degree-granting institutions on behalf of individual researchers. To complement these competitive award programs, Burroughs also makes grants to nonprofit organizations conducting activities intended to improve the general environment for science.