Apr 25 2025

Biophysics Seminar- “A free-solution method to measure physiological interactions of lipid and lipid G-protein coupled receptors (GPCRs)” with Prof. Manisha Ray (Loyola University Chicago)

Biophysics Seminar

April 25, 2025

2:00 PM - 3:00 PM

"A free-solution method to measure physiological interactions of lipid and lipid G-protein coupled receptors (GPCRs)"
Dr. Manisha Ray
Assistant Professor
Loyola University Chicago

The conformational change and binding of lipid GPCRs to bioactive lipids in the native environment has traditionally been difficult to measure and interpret in vitro. Hence, direct binding affinities are scarce in the lipid-GPCR interaction field. Usual receptor binding studies employ highly overexpressed and/or modified receptors, in addition to labeled ligands, which can affect results in unpredictable ways using conventional labeling or assays with immobilizing approaches. However, a free-solution assay method in combination with a light interferometry technology has the capability to measure such physiologically relevant binding affinities with unprecedented sensitivity at the picomolar to femtomolar level. We have used this method to determine the binding interaction between Lysophosphatidic acid (LPA) and its cognate receptors. LPA is a bioactive lipid and its signaling to Lysophosphatidic acid receptors (LPA1 through LPA7) has been
linked to cancer, inflammation, metabolic disorders, including some neurological disorders. In my talk, I will discuss some potential results of different lysophosphatidic acids (LPA) binding to LPA1 and its mutants, including measurement of specificity of some structure guided synthetic analogs of LPA1,2 agonists and antagonists. Following this, we also determined direct KDs and specificities of some FDA approved drugs in relevance to multiple sclerosis (MS) disease mechanism. Finally, I will quickly highlight my current work at Loyola University Chicago on lipid-chaperone interactions to probe lipid delivery mechanism to GPCRs by primarily focusing on albumin.

Contact

Huan-Xiang Zhou and Fidha Kunnath Muhammedkutty

Date posted

Jan 15, 2025

Date updated

Apr 19, 2025