Analysis of biased signalling responses through CXCR4 and CXCR7

Early stage researcher 9 (ESR9) project – Davide Capoferri
Supervision: Prof G Milligan, Prof G Graham.
Host: UGL (UK) – University of Glasgow, Institutes of i) Molecular Cell and Systems Biology and ii) Infection, Immunity and Inflammation.
 

I- Project proposal:

Aim:
1. To determine the impact of β-arrestin/G protein deficiency on CXCR4/ CXCR7, or heteromer function and signalling.

2. To analyze the efficacy of CXCR4 and CXCR7 modulators in G protein and β-arrestin-dependent pathways using label free technologies.

Methodology:
This project will capitalise on the availability, to our group, of a unique cellular resource allowing for conditional, and selective, expression of β-arrestin proteins in HEK cells. These cells will be transfected with CXCR4 and/or CXCR7 and signalling output and hetero/homodimeristion assessed in the presence, or absence, of arrestin expression. Receptor dimerisation will be examined (in the presence or absence of arrestin expression) using FRET-based approaches. These cells will also be used to test the effects of co-expression of CXCR4 and CXCR7 on directional cellular migration using time-lapse migration assays and, again, the dependence of these effects on arrestin signalling will be investigated. If time permits, we will also use these approaches to analyse the β-arrestin dependency of signalling and function in other members of the Atypical Chemokine receptor family. Planned secondments: UAM (ES), Cisbio (FR).

 

II- Requirement candidate:

Required diploma: MSc degree in a relevant biological science. Candidates with degrees in biochemistry or pharmacology are particularly encouraged to apply.

Required expertise: Biochemistry, molecular biology, cell culture.

Recommended expertise: Chemokine biology, GPCR biochemistry, protein chemistry.

Key publications:
1. Nibbs RJB, Graham GJ: Immune regulation by atypical chemokine receptors, Nature Reviews Immunology 2013, 13:815-829.

2. Lee KM, Danuser R, Stein JV, Graham D, Nibbs RJB, Graham GJ. The chemokine receptors ACKR2 and CCR2 reciprocally regulate lymphatic vessel density. The EMBO Journal 2014, 33, 2564-2580

3. Butcher, A.J., Hudson, B.D., Shimpukade, B., Alvarez-Curto, E., Prihandoko, R., Ulven, T., Milligan, G. and Tobin, A.B. (2014) Concomitant action of structural elements and receptor phosphorylation determine arrestin-3 interaction with the free fatty acid receptor FFA4. J Biol Chem 289, 18451-18465

4. Hudson, B.D., Christiansen, E., Murdoch, H., Jenkins, L., Højgaard Hansen, A., Madsen, O., Ulven, T. and Milligan, G. (2014) Complex pharmacology of novel allosteric Free Fatty Acid 3 Receptor ligands. Mol Pharmacol 86, 200-210.

Follow us on

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

My project will be focused on the role of #CXCR4/ACKR3/GRK2 -governed networks in cancer cell migration and metastasis.

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.

Hey twitter!
I am @DehanComez. I am taking over the Oncornet account for a while to start a series of all #ESRs writing about themselves and their projects. I am #ESR5, originally from Turkey and right now I am working as a PhD student in @COMPARE_UoBUoN , @UniofNottingham , UK.

New review on #gpcr structural dynamics out in COSB. Great teamwork with the @JanaSelent group. Thanks to @Lundbeckfonden and @novonordiskfond https://lnkd.in/eyjrA5V

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!

Hi everyone!

Public service announcement: our Marie-Curie ITN @ONCORNET1 is on Twitter! The 16 wonderful #ECRs working on the project will soon be Tweeting about #GPCR #chemokine #ECR life and #pharmacology

Please #RT & consider a follow or follow back! 🙏😀

Load More…

Contact details

Please contact us at:
info@oncornet.eu

ONCORNET Coordinator
VU University Amsterdam
The Netherlands