SVC Research Seminar - "Phase Separation as a Compartmentalization Strategy and Antibiotic Target in Bacteria"

Phase Separation as a Compartmentalization Strategy and Antibiotic Target in Bacteria

W. Seth Childers, PhD, assistant professor of chemistry, Dietrich School of Arts and Sciences, will present a Senior Vice Chancellor’s Research Seminar, “Phase Separation as a Compartmentalization Strategy and Antibiotic Target in Bacteria.”

Registration for the lecture is required to receive event instructions.

Topic Overview: 

A defining difference between bacteria and eukaryotes is the lack of organelles in bacteria. Recently, phase separation of proteins as biomolecular condensates has been recognized as a fundamental way to organize biochemistry as a “membraneless organelle.” Childers will describe his and colleagues’ discoveries of how biomolecular condensates organize and regulate mRNA decay and signal transduction in bacteria. These discoveries suggest a new view of the bacterial cytoplasm as a crowded “bag of biomolecular condensates.”

One significant challenge is understanding whether biomolecular condensates have any functional significance. Toward these goals, Childers and colleagues have developed a fluorescence biosensor imaging strategy to visualize changes in histidine kinase structure with subcellular resolution. Application of this engineered fluorescence resonance energy transfer (FRET) biosensor visualized that cell pole localized membraneless organelles alter the structure of this critical cell-fate determinant. Thus, this FRET biosensor strategy provides a way to interrogate the functions of biomolecular condensates in cells. 

Given the importance of biomolecular condensates to cell physiology, are they ultimately druggable antibiotic targets? Childers and colleagues have examined strategies for disrupting the phase separation of the chromosome segregation protein and have discovered a small molecule that inhibits this process. Childers will also discuss the general understanding of how small molecules specifically partition into biomolecular condensates. The development of new chemical biology tools targeting condensates will enhance understanding of how enzymes function in these environments, lead to new specific stains for condensates, and reveal how they may affect antibiotic pharmacokinetics.