Compartmentalised signalling and trafficking of CXCR4 and ACKR3

Early stage researcher 11 (ESR11) project
Supervision: Prof. Dr. Meritxell Canals, Dr. Stephen Briddon
Host: University of Nottingham

I – Project proposal:

Aim: 

  1. To investigate the compartmentalization of signals generated by CXCR4 and ACKR3.

  2. To assess receptor diffusion within the plasma membrane and endocytosis and to determine its role in the signalling repertoire of CXCR4 and ACKR3.

  3. To use receptor mutatagenesis and knockdown of GRKs, G proteins and arrestins to elucidate the mechanisms of signal compartmentalisation and receptor regulation. 

Methodology:
Signal compartmentalization by CXCR4 and ACKR3 will be investigated using genetically encoded biosensors that detect activation of specific signalling cascades (PKC, ERK, cAMP).

Receptor diffusion within the plasma membrane will be assessed using Fluorescence Correlation Spectroscopy (FCS) as well as Total Internal Reflection Fluorescence (TIRF) microscopy. BRET sensors for receptor trafficking and for the recruitment of arrestins will be used to determine the kinetics of receptor endocytosis.

The mechanisms of compartmentalised signalling and receptor trafficking, and the relation between them will be assessed using complementary approaches to inhibit receptor endocytosis in combination with the signalling biosensors and imaging approaches described above.

Planned secondments:

Universitätsklinikum Jena

Universidad Autónoma de Madrid  

 

II – Requirement candidate:

Required diploma: MSc degree in pharmacology, biochemistry or a related discipline

Required expertise: cell culture, cell biology, cell-based assays, molecular biology

Recommended expertise: GPCR molecular pharmacology, imaging, FRET/BRET-based approaches

Key publications:

  1. Halls, M.L., et al., Plasma membrane localization of the μ-opioid receptor controls spatiotemporal signaling. Science signaling, 2016. 9(414): p. ra16.
  2. Gondin, A.B., et al., GRK Mediates mu-Opioid Receptor Plasma Membrane Reorganization. Front Mol Neurosci, 2019. 12: p. 104
  3. Jensen, D.D., et al., Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolong ed pain relief. Science translational medicine, 2017. 9(392).
  4. Briddon, S.J., L.E. Kilpatrick, and S.J. Hill, Studying GPCR Pharmacology in Membrane Microdomains: Fluorescence Correlation Spectroscopy Comes of Age. Trends in pharmacological sciences, 2018. 39(2): p. 158-174.

For more information:
Prof. Dr. Meritxell Canals – meritxell.canals@nottingham.ac.uk

Dr. Stephen Briddon – stephen.briddon@notthingham.ac.uk

 

Application:

Apply here 

Follow us on

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

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