ChBE Seminar Series - 3:30 p.m. EDT Thursday March 3 - Seth Childers

Thu Mar 3 3:30 pm to 4:30 pm
MoSE G011

Seth ChildersProfessor W. Seth Childers, University of Pittsburgh (joint presentation with School of Chemistry and Biochemistry)

"Biomolecular condensates as a compartmentalization strategy in bacteria"

3:30 p.m. MoSE G011 (Virtual option: https://bluejeans.com/764447847 )

 

Abstract:

One defining difference between bacteria and eukaryotes is the absence of membranebound organelles in bacteria. Recently, phase separation of proteins as biomolecular condensates has been recognized as a fundamental way to organize subcellular space 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 further suggest a new understanding of the bacterial cytoplasm as a crowded "bag of biomolecular condensates." One significant challenge in cell biology is understanding if these membraneless organelles have any functional significance? To consider the function of biomolecular condensates in vivo, the Childers lab engineered a fluorescence biosensor imaging strategy to visualize changes in histidine kinase structure with subcellular resolution. Application of this engineered FRET biosensor visualized that cell pole localized membraneless organelles alter the structure of a critical cell-fate determining protein. Thus, this FRET biosensor strategy provides a strategy to demonstrate the functional significance of biomolecular condensates. It may also be utilized to map signals perceived by two-component systems. Given our new understanding of the molecular organization of the bacterial cytoplasm, we considered the potential of biomolecular condensate in bacterial synthetic biology. Towards this goal, we revisited the phase properties of a family of ABC triblock peptide nanomaterials that forms hydrogels for drug delivery at high weight percent. We found ABC triblock proteins assemble as gel-like biomolecular condensates at low micromolar concentrations in vitro. Moreover, expression of the coiled-coil triblock peptides in bacteria leads to cell pole accumulation that could sequester clients at the cell pole with the potential to serve as synthetic membraneless organelles in bacteria. In summary, our studies suggest that phase separation allows bacteria to form membraneless organelles that alter our view of bacterial cell biology and present new opportunities in synthetic biology and new antibiotic targets.

Bio:

Professor Seth Childers received his B. ChE. degree from the Georgia Institute of Technology in 1999 and worked as a process engineer in the pharmaceutical industry at Merck until 2004. He completed his Ph.D. in biological chemistry at Emory University in 2010 under the mentorship of Professor David G. Lynn. His graduate studies examined amyloid's phase properties and catalytic capabilities, the causative agent of Alzheimer's Disease. From 2010 to 2015, he was a postdoctoral scholar gaining expertise in bacterial signal transduction in Professor Lucy Shapiro's and Harley McAdams’s group at Stanford University. He joined the Department of Chemistry at the University of Pittsburgh in September 2015. His lab has three major research thrusts. One in the area of biomolecular condensates as organizers of mRNA decay and signal transduction processes in bacteria. A second in the development area of research is the development of synthetic biology tools to study gut-brain axis dysregulation. The third area of research has studies mechanisms of how scaffolding proteins and pseudokinases regulate bacterial signaling pathways critical for growth, division, and pathogenesis. Towards these research thrusts, the Childers lab applies protein engineering, synthetic biology, microbiology, and biochemistry within each of these research thrusts. He has published eleven peer-reviewed publications, including two papers in Molecular Cell, two in ACS Synthetic Biology, one in ACS Sensor, and one in JBC. Dr. Childers has received two Scialog Fellow Awards as a part of the Chemical Machinery of the Cell 2020-2021 meetings. His research is supported by the NIH and Research Corporation for Scientific Advancement.

Location

MoSE G011