In situ analysis of CXCR4 and CXCR7 ligand-binding and spatio-temporal localization using imaging tools on ex vivo samples

Early stage researcher 15 (ESR15) project – Sabastian Dekkers
Supervision: Dr M Stocks, Prof S J Hill, Dr S J Briddon, Prof B Kellam
Host: UNOTT (UK) – University of Nottingham, Schools of Pharmacy and Life Sciences

I- Project proposal:

1. Development, optimization and characterization of fluorescent ligands for CXCR4 and CXCR7 for use in fluorescence-activated cell sorting (FACS) analysis and high content confocal microscopy.

2. Evaluation of spatio-temporal CXCR4 and CXCR7 localization and trafficking in ex vivo (patient) samples using high content confocal imaging.

3. CXCR4 and/or CXCR7-selective profiling of patient blood samples and relationship to functional activity in isolated cells.

Standard medicinal chemistry approaches will be used to generate fluorescent ligands for the CXCR4 and CXCR7 receptors. Fluorescent ligand binding will be monitored using confocal microscopy, automated confocal imaging plate readers, FACS and also BRET and TR-FRET methodologies using standard plate readers (with SNAP and Nanoluc tagged receptors). Planned secondments: Vivia Biosystems (ES), Actelion (CH).


II- Requirement candidate:

Required diploma: MSc degree in medicinal chemistry or related discipline Required expertise: medicinal chemistry, cell culture, cell-based assays.
Recommended expertise: GPCR molecular pharmacology, imaging, FRET/BRET based signalling, ligand binding studies. 

Key publications:
1. Longden J, Cooke EL, Hill SJ. (2008) Effect of CCR5-receptor antagonists on endocytosis of the human CCR5 receptor in CHO-K1 cells. Br J Pharmacol. 153: 1513-1527.

2. Stoddart LA, Vernall AJ, Denman JL, Briddon SJ, Kellam B. Hill SJ. (2012). Fragment screening at adenosine A3-receptors in living cells using a fluorescence-based binding assay. Chem Biol. 19: 1105-1115.

3. Corriden R, Kilpatrick LE, Kellam B, Briddon SJ and Hill SJ (2014) Kinetic analysis of antagonist-occupied adenosine A3-receptors within membrane microdomains of individual cells provides evidence of receptor dimerization and allosterism. FASEB J 28: 4211-22.

4. Corriden R, Self T, Akong-Moore K, Nizet V, Kellam B, Briddon SJ, Hill SJ (2013) Adenosine A3 receptors in neutrophil microdomains promote the formation of bacteria-tethering cytonemes. EMBO Rep. 14: 726-732.

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Great way to finish the week off with some #FCS measurements of CXCR4-expressing HEK cells at @UoNLifeSci 🔬 #FluorescenceFriday

Hello everyone!
I am Noemi Karsai and I’m the next in our #ESR introduction series. I’m #ESR11 and I’m originally from Hungary, currently doing my PhD at @UoNLifeSci @COMPARE_UoBUoN, UK.

The transatlantic ECI GPCR symposium #ECIGPCR is about to start, we are ready!! Thanks to the organizers for their excellent job gathering almost 500 people across the globe! @cyclic_Andreas @NicoleAPerry1 @BenderSci @DesislavaNeshe1

Hello 🙂
I am here to continue the series in which all #ESRs are presenting themselves. I am Viviana Marolda and I am in my first year of PhD. I am #ESR13, originally from Italy, and currently, I am working as a PhD student in @CBMSO_CSIC_UAM, at Universidad Autonoma de Madrid.

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New review on #gpcr structural dynamics out in COSB. Great teamwork with the @JanaSelent group. Thanks to @Lundbeckfonden and @novonordiskfond

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:

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!

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Contact details

Please contact us at:

ONCORNET Coordinator
VU University Amsterdam
The Netherlands