Visualizing liver nuclear receptor phospholipid membrane exchange

The nuclear receptor NR5A2 is well known to bind and be regulated by phospholipids - even an exogenous plant phospholipid called DLPC was recently found to activate NR5A2 having dramatic anti-diabetic effects in the mouse liver. However, how those phospholipids leave cellular membrane systems and come to bind NR5A2 is completely unexplored. The most salient reason why this is such an understudied area of nuclear receptor biology is because the fluorescent tools needed to track phospholipid "movement" or "exchange" between NR5A2 and cellular membranes have not been developed. This pilot will develops those tools, levearging the outstanding expertise of the investigator to generate & purify stable complexes of NR5A2 bound to fluorophore labeled phosholipids. These tools will permit us to ask project-level questions about how NR5A2 comes to possess phospholipid, having implications for better modeling of NR5A2-mediated phospholipid physiology in the liver, better approaches for NR5A2 drug design efforts and a better understanding of how the exogneous phospholipid DLPC activates NR5A2.