Project Details
Projekt
Modulating Class B1 GPCR Signaling: Structural and Functional Elucidation from a Heterochiral Design Strategy
Applicant
Dr. Nishu
Subject Area
Biological and Biomimetic Chemistry
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 576334292
The proposed research aims to elucidate the structure and function of Class B1 G protein-coupled receptors (GPCRs), specifically glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like -peptide-2 receptor (GLP-2R). Recent cryo-EM structures have provided valuable insight into the static conformations observed almost universally among agonist peptides bound to class B1 receptors may not fully elucidate the mechanisms that transmit signals through these receptors to the cell interior. The proposed heterochiral approach with systematic replacement of L-amino acid residues with D-amino acid residues in polypeptide hormones (GIP and GLP-2) might give insights to understand the role of agonist dynamics in signal transduction. Combining peptide synthesis, molecular biology, cell-based assays, and computational modeling, this work will pinpoint key determinants of agonist efficacy and stability. Ultimately, this research will provide the new tools for mapping and modulating signal transduction mechanism of class B1 GPCRs, accelerating innovative therapeutic discovery.
DFG Programme
WBP Fellowship
International Connection
USA
