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:
- Hauwert et al., J. Am. Chem. Soc. 2018, 140, 4232
- Hauwert et al., Angew. Chem. Intl. Ed. 2019, 58, 4531
- Gómez-Santacana et al., Angew. Chem. Intl. Ed. 2018, 57, 11608
- 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:
Follow us on
My project will be focused on the role of #CXCR4/ACKR3/GRK2 -governed networks in cancer cell migration and metastasis.
New review on #gpcr structural dynamics out in COSB. Great teamwork with the @JanaSelent group. Thanks to @Lundbeckfonden and @novonordiskfond https://lnkd.in/eyjrA5V
A reminder that applications for our new Deputy Editor in Chief of #PharmacologyMatters close on Monday. https://buff.ly/2PNWf4V
ONCORNET2.0 is the successor to #ONCORNET. You can see some of the work of ESRs from the first ONCORNET in this special issue of @MolPharmJournal from 2019, with reviews on #CXCR4 and #ACKR3 structure and function: https://molpharm.aspetjournals.org/content/96/6
Hi everyone – we’re on Twitter! ONCORNET2.0 is a #MarieCurie ITN of 16 ESRs across Europe studying #chemokine #GPCRs #CXCR4 and #ACKR3 in cancer. Our projects cover molecular dynamics, medchem, #pharmacology through to translational work. Follow us for updates from our ESRs!
Contact details
Please contact us at:
info@oncornet.eu
ONCORNET Coordinator
VU University Amsterdam
The Netherlands