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Towards high-affinity ligands for orphan receptors GPR3, GPR6 & GPR12

Objective

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.

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Keywords

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Programme(s)

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2021-PF-01

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Coordinator

PHILIPPS UNIVERSITAET MARBURG
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 189 687,36
Address
BIEGENSTRASSE 10
35037 Marburg
Germany

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Region
Hessen Gießen Marburg-Biedenkopf
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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