W. Seth Childers, Assistant Professor, Department of Chemistry, University of Pittsburgh, will give a seminar on "Biomolecular condensates as organizers of biochemistry in bacteria."

ABSTRACT

One defining difference between bacteria and eukaryotes is the absence of membrane-bound organelles in bacteria. Recently, a second fundamental compartmentalization strategy in eukaryotes has been recognized that relies upon phase separation of scaffolding proteins. These assemblies lack a membrane barrier but can organize and sequester biochemistry as a “membraneless organelle.” Here, we will describe our discoveries of how biomolecular condensates organize and regulate mRNA decay and signal transduction processes in bacteria. Overall, our discoveries combined with those from other labs suggest a new image of bacteria as a "bag of biomolecular condensates."

One significant challenge in cell biology is understanding if these membraneless organelles have any functional significance? Towards this goal, the Childers lab has characterized how phase separation impacts ribonuclease and kinase enzyme kinetics in vitro. They found that activation of a signaling protein's function was coupled to phase separation of the signaling complex, which may present a generalizable way to regulate low copy signaling in cells in an all-or-none fashion. To consider the function of biomolecular condensates in vivo, the Childers lab has developed a fluorescence biosensor imaging strategy that visualized how membraneless organelles impact
the structure of a bacterial signaling protein critical for asymmetric cell division in Caulobacter crescentus. Finally, the Childers lab applied a chemical genetics approach to interrogate the importance of phase separation towards bacterial physiology. They identified a small molecule that inhibits phase separation of an essential bacterial biomolecular condensate that regulates chromosome segregation. In summary, our studies suggest that phase separation provides bacteria with a generalizable compartmentalization strategy, and disruption of phase separation may present an actionable antibiotic target.