Structure-function relationships of GALR2 signalling

• Grant number: 19/07476-7
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2019
• End date: April 30, 2022
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Agreement: University of Nottingham
• Principal Investigator: Daniela Barretto Barbosa Trivella
• Grantee: Daniela Barretto Barbosa Trivella
• Principal researcher abroad: Leigh Shearer
• Institution abroad: University of Nottingham, University Park, England
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated researchers: Carolina Aparecida de Guzzi Cassago ; Danieli Cristina Gonçalves ; Stephen John Hill

Abstract

G protein coupled receptors (GPCRs) are transmembrane proteins with essential roles in physiology and disease. They enable cells to respond to stimuli by ligands, such as peptides, neurotransmitters, lipids, hormones, carbohydrates, glycoproteins, ions, photons and odorants, and are the targets of many drugs used in the clinic. The signalling pathways and protein structures associated with selected GPCRs have been explored in depth. However, pathways associated with peptide stimulated GPCRs, such as the galanin receptor 2 (GALR2), remain poorly understood despite their important physiological roles. GALR2 is involved in a range of processes including nociception, memory, intestinal secretion and contractility and deficiencies in the galanin-GALR2 axis are linked to pathologies such as cancer and multiple sclerosis. This proposal aims to deliver fundamental new information on the molecular pharmacology and structure of GALR2, which can in the future be used to develop approaches for its pharmacological modulation. In addition, this project will strengthen an existing UK-Brazil collaboration and consolidate GPCR structure elucidation by cryo-EM in Brazil. (AU)