Postdoctoral Fellowship: PRFB: Elucidating the Relationship Between Structure and Enzymatic Activity in PopZ Condensates

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2025. The fellowship supports research and training of the fellow that will contribute to biology in innovative ways. The project explores the role of so-called biomolecular condensates that exist in cells as concentrations of molecules and modulate biochemical reactions.

Interestingly, the condensates act like a cellular compartment but are not bounded by a membrane. Specifically, the research will investigate how the physical and chemical properties of biomolecular condensates influence the activity of enzymes recruited into them. The mechanisms are poorly understood.

Therefore, this project addresses a key open question: How are enzyme-catalyzed reactions within a condensate influenced by the condensate’s properties? In addition to increasing our understanding of regulation of cellular function, filling this gap in knowledge will allow bioengineers to harness biomolecular condensates as therapeutic tools.

To investigate the effects of specific condensate properties on enzymatic activity, the fellow will receive training in a variety of advanced imaging techniques, including cryo-electron tomography and single-molecule MINFLUX super-resolution microscopy, and combine these with his existing expertise in protein biophysics. The research will leverage the well-characterized scaffold protein PopZ to systematically alter condensate properties through targeted mutations.

By incorporating a model enzyme and its substrate within these engineered condensates, the study will directly assess how variations in condensate architecture influence enzymatic activity. The findings will deepen our understanding of how cells exploit condensate properties to fine-tune biochemical reactions. A further impact of this research, with important potential benefits to society, is that its results will help bioengineers realize the potential of custom-designed protein condensates for therapeutic applications that require precise tuning of material properties and function.

In addition, the fellow will continue to mentor junior scientists to raise the next generation of biophysicists.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.