Anshuman Jaysingh

Program: Biochemistry Biophysics and Structural Biology

Current advisor: Andrea Soranno, PhD

Undergraduate university: Indian Institute of Science Education and Research, Kolkata, 2022

Enrollment year: 2022

Research summary
Biophysical studies of interaction of ApoE with lipids, linking conformations, lipid composition and membrane biophysics in the context of Alzheimers and Cardiovascular disease

I study how subtle sequence differences in apolipoprotein E (ApoE) rewire its interactions with lipid membranes and native lipoproteins—mechanisms that sit at the crossroads of cardiovascular disease and Alzheimer’s disease. Using single-molecule FRET with domain-specific labels, fluorescence correlation spectroscopy, and temperature-controlled assays, I quantify isoform-dependent binding affinities, pinching/budding kinetics from synthetic liposomes, and the redistribution of compact vs expanded lipid-bound conformations. I then tune membrane biophysics—phase state, cholesterol content, headgroup chemistry, and acyl-chain saturation—to mimic HDL/LDL/VLDL surfaces, and extend measurements to plasma-derived particles. Complementary coarse-grained and atomistic simulations (thermal unfolding + membrane binding) provide structural interpretations of the smFRET observables and identify conformation-specific binding modes. Together, this work connects ApoE sequence, conformational stability, and membrane physics to explain why isoforms partition differently across lipoprotein classes, informing strategies to modulate ApoE-lipid interactions in CVD and AD.

Graduate publications