Obiettivo
The family of G protein-coupled receptors (GPCRs) comprises more than 800 human cell surface receptors that perceive and transmit extracellular stimuli into the cell interior. Due to their involvement in numerous biochemical processes, GPCRs represent prime targets for the treatment of various diseases and are modulated by more than 30% of approved drugs today. However, a large proportion of the druggable GPCRome remains pharmacologically untapped, including the so-called ‘orphan’ GPCRs (oGPCRs) - receptors for which the endogenous ligands remain unknown.
GPR3, 6 and 12 constitute a cluster of orphan GPCRs that is involved in numerous (patho-)physiological processes including neurodegenerative disorders such as Parkinson’s and Alzheimer’s dementia. GPR3 and GPR12 further mediate meiotic arrest in oocytes and suppress the development of metabolic diseases. Other physiological processes and diseases associated with GPR3/6/12 are neuropathic pain perception, addiction and different forms of cancer. Although these receptors represent promising pharmacological targets and researchers have been trying to discover molecules targeting these receptors for more than two decades, only a limited set of five ligands is currently available. Modern GPR3/6/12-targeted drug discovery is still hampered by the lack of verified endogenous ligands, our poor understanding of their structural organization and signalling cascades promoted by these receptors, and a limited panel of assays revealing GPR3/6/12 activity in living cells.
Here, I propose to implement an interdisciplinary research approach combining computational methodologies with advanced biosensor technology in order to discover advanced ligands for these attractive drug targets. These novel compounds will aid in developing advanced therapeutics tackling severe human diseases and our reseach will highlight the power of interdisciplinary drug discovery approaches, promoting their implementation in the GPCR field and beyond.
Campo scientifico
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicineneurologyparkinson
- natural sciencescomputer and information sciencesartificial intelligencecomputational intelligence
Parole chiave
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinatore
35037 Marburg
Germania