Pressure-Jump NMR of Aggregating Systems

Proteins are biological macromolecules that are essential for life.

Organization and compartmentalization processes play central roles in biology, both of which are driven by biomolecular events such as transient protein oligomerization and liquid-liquid phase separation (LLPS).

It is emerging that LLPS is a ubiquitous mechanism by which living cells localize, and organize, biomolecules in both space and time, to perform myriad functions.

Very recently, it was demonstrated that LLPS is readily reversible on application of experimentally accessible hydrostatic pressures.

This discovery presents an opportunity to investigate LLPS using the powerful new technique of Pressure-Jump Nuclear Magnetic Resonance (PJ-NMR) spectroscopy developed in the Bax group (NIH, USA).

PJ-NMR instruments can change the pressure of a solution NMR sample between 1 bar and 2500 bar in only a few milliseconds, which enables direct observation of biomolecules entering the condensed (or oligomeric) state with unprecedented time/spectral/dynamic resolution.

I have identified several systems of biomedical interest where LLPS/oligomerization processes are pressure-reversible, and this project proposes to explore the specific molecular interactions, dynamic processes, and environmental conditions that drive them.

A handful of people in the world have experience using the PJ-NMR apparatus, and fewer still have experience with both the engineering and biochemical sides of the project. I am one of that number.