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  ONCOgenic GPCR Network of Excellence and Training




Early stage researcher 8 (ESR8) project

Supervision: Prof. Dr. Carsten Hoffmann, Dr. Julia Drube

Host: Universitätsklinikum Jena


I - Project proposal:

Our current knowledge is very limitted with respect to GPCR/arrestin interaction and the role of individual GRKs in this process. Most of the GPCR-family members are regulated by only four of the seven members of the GRK-family (namely GRK 2,-3,-5, and -6) and two of the four arrestin proteins that exist in human physiology, namely β-arrestin 1 and β-arrestin 2. For this system of GPCR regulation to be conceivable, β-arrestins require the ability to adopt to a multitude of different receptor activation and phosphorylation states, supposedly facilitated by a high degree of conformational plasticity within β-arrestin. 


  1. Characterization of the ligand dependent conformational signature of CXCR4/ACKR3 in β-arrestin-1 and -2 using FRET and BRET sensors for conformational changes in β-arrestin-1/2.
  2. Characterization of phosphorylation dependent conformational signature of CXCR4/ACKR3 in β-arrestin-1/-2 using site-directed mutagenesis and GRK specific knock-down (CRISPR/Cas9) in HEK293 cells. 
  3. The conformational signatures obtained will further be evaluated for differential signaling and/or localization of the respective chemokine receptor.




We will use a combination of site-directed mutagenesis of identified phosphorylation sites, pharmacological tools (GRK2 or GRK5 inhibition), and knock-down approaches (siRNA or CRISPR/Cas9 for GRKs using HEK293 cells) to study the individual effect of phosphorylation sites in coupling to β-arrestin.

Furthermore, FRET and BRET-based sensors will be developed and employed to study concentration dependent conformational changes of arrestin in real time and living cells. Confocal microscopy (including high-resolution) will be used to study the individual effects of phosphorylation sites in receptor localization. 


Planned secondments:  

Universidad Autónoma de Madrid (Prof. Federico Mayor)

Vrije Universiteit Amsterdam (Prof. Dr. Martine Smit)



II - Requirement candidate: 

Required diploma: MSc degree in life or natural sciences (e.g. biology, biochemistry, molecular biology, pharmacy or related disciplines)

Required expertise: biochemistry, molecular biology

Recommended expertise: Knowledge of basic cell culture, microscopy and imaging techniques (fluorescence of bioluminescence resonance energy transfer). Basic knowledge of ImageJ, Prism, Origin would be a plus. Knowledge of siRNA or CRISR/Cas9 would be a bonus.


Key publications:

  1. S. Nuber, U. Zabel, K. Lorenz, A. Nuber, G. Milligan, A.B. Tobin, M.J. Lohse, C. Hoffmann (2016) β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle. Nature Mar 31;531(7596):661-4; doi: 10.1038/nature17198. Epub 2016 Mar 23.

  2. R.S. Haider, A. Goodbole, C. Hoffmann (2019) To sence or not to sence - New insights from GPCR and arrestin biosensors. Current opinion in Cell Biology, 57: 16-24 doi: 10.1016/

  3. J. Heuninck, C. Perpiñá Viciano, A. Işbilir, B. Caspar, D. Capoferri, S.J. Briddon, T. Durroux, S.J. Hill, M.J. Lohse, G. Milligan, J.-P. Pin, and C. Hoffmann (2019) Context-dependent signalling of CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) MolPharm, in press, doi: 10.1124/mol.118.115477


    For more information:

    Prof. Dr. Carsten Hoffmann - This email address is being protected from spambots. You need JavaScript enabled to view it.



Please send your application to This email address is being protected from spambots. You need JavaScript enabled to view it. 

Include in heading - ONCORNET2.0 application + ESR#

Contact details

Please contact us at:

ONCORNET Coordinator
VU University Amsterdam
The Netherlands

Funded by

marie curie actions   Marie Curie Actions



EU Horizon 2020



european union logo   European Union