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:

1. Hauwert et al., J. Am. Chem. Soc. 2018, 140, 4232
2. Hauwert et al., Angew. Chem. Intl. Ed. 2019, 58, 4531
3. Gómez-Santacana et al., Angew. Chem. Intl. Ed. 2018, 57, 11608
4. Gómez-Santacana et al., Beilstein Arch. 2019, doi:10.3762/bxiv.2019.69.v1 

For more information:
Prof. Dr. Rob Leurs – r.leurs@vu.nl

Dr. Henry Vischer – h.vischer@vu.nl

Dr. Maikel Wijtmans – m.wijtmans@vu.nl

Application:

Apply here