Professor Cegelski is an Assistant Professor of Chemistry at Stanford University. She received her Ph.D. in Chemistry from Washington University working with Professor Jacob Schaefer and trained as a Microbiology postdoctoral fellow in the laboratory of Prof. Scott Hultgren at the Washington University School of Medicine. The Cegelski laboratory is developing new strategies using macromolecular and whole-cell solid-state NMR spectroscopy together with new biochemical protocols to characterize and manipulate bacterial cell wall and biofilm assemblies. These efforts are coupled with small-molecule discovery efforts to identify potential new anti-infectives. Prof. Cegelski is the recipient of the Burroughs Wellcome Career Award at the Scientific Interface (2008), the NIH Director’s New Innovator Award (2010), and the NSF CAREER Award (2015)
Bacterial Cell-Wall and Biofilm Discoveries with Small Molecules and a Big Magnet
The bacterial cell wall is essential to cell survival and is a major target of antibiotics. Beyond the cell sur- face, bacteria assemble complex macromolecular architectures during biofilm formation. Biofilms are implicated in serious infectious diseases and have emerged as a target for anti-infectives. Our research program is inspired by the challenge and importance of elucidating chemical structure and function in these complex biological systems and we strive to transform our discoveries into new therapeutic strategies. We have introduced uniquely enabling approaches using whole-cell and macromolecular solid-state NMR, integrated with new protocols for microscopy and biochemical analysis, in order to reveal how the physical properties and biological functions of cell walls and biofilms depend on their chemical composition and architecture. We are using this approach to probe the modes of action of newly discovered antimicrobials and anti-virulence compounds, including a number of promising compounds we have identified through our own high-throughput screening efforts. I will report on our major discoveries including the first determination of the composition of the intact biofilm extracellular matrix, the biosynthetic production of a modified cellulose in this matrix, and small-molecule activities that tip Nature off balance to probe the assembly and function of the component structures.
Artist: Hava Friedman Logo design: Nick Kotoulas, Jennifer Tran Photography: Nick Kotoulas