Pharmacological analysis of photoactivatable CXCR4/ACKR3 ligands in vitro/in vivo

Early stage researcher 7 (ESR7) project
Supervision: Prof. Dr. Rob Leurs, Dr. Henry Vischer, Dr. Maikel Wijtmans
Host: Vrije Universiteit Amsterdam

I- Project proposal:

Aim:
The project aims for the development of photopharmacological approaches for the CXCR4 and ACKR3 chemokine receptors. New assays to dynamically modulate these chemokine receptor systems with light-switchable ligands will be developed. Main focus will be on in vitro, cell-based assays, but ultimately light-induced in vivo modulation of CXCR4 and/or ACKR3 function is the final aim within this project.

Methodology:
This project will entail the assay development of new photopharmacology assays to evaluate photoswitchable small-molecule CXCR4 and ACKR3 ligands (agonists/antagonists). The characterization of new photoswitchable ligands can be supported by computer-aided drug design and GPCR mutation studies where necessary. Design and synthesis of photoswitchable ligands will be conducted by fellow ESR1.

Planned secondments:

InterAx (Switserland) – candidate will get exposed to relevant dynamic cell-based assays.

INSERM (Paris, France) – candidate will work on biological characterization of photoswitchables compounds in relevant models of disease.

II – Requirement candidate:

Required diploma: A MSc degree in Biochemistry or Pharmacology or related Biomedical degrees

Required expertise: The candidate has a strong background (theoretical and practical) in cell biology, signal transduction and preferably pharmacology and/or molecular biology.

Recommended expertise: Expertise in GPCR molecular and cellular pharmacology is a strong pre. Previous experience with biosensor-based assay development and/or photopharmacology is also highly valued

Key publications: