Super-resolution spatiotemporal analysis of CXCR4/ACKR3 signalling nanodomains
Early stage researcher 6 (ESR6) project
Supervision: Prof. Dr. Martin Lohse, Dr. Paolo Annibale, Dr. Andreas Bock
Host: Max Delbrück Center for Molecular Medicine in der Helmholtz Association, Berlin, Germany
I- Project proposal:
Aim:
We aim for an analysis of where, when, and how fast receptors become activated. We will use most advanced microscopy and cell biology techniques to generate images and films of how these processes happen.
Methodology:
Photo-switching of receptor FRET-sensors, analysis of activation kinetics and signal propagation of CXCR4/ACKR3 with sub-millisecond resolution. Analysis of receptor activation and signal compartmentation with super-resolution microscopy and fluctuation analysis. Mapping of CXCR4/ACKR3 signalling nanodomains with receptor/sensor fusion constructs
Planned secondments:
Vrije Universiteit Amsterdam – characterization of CXCR4/ACKR3 photo-switchable ligands
University of Nottingham – superresolution imaging of CXCR4-and ACKR3 and their signals
II – Requirement candidate:
Required diploma: Master in natural or life sciences
Required expertise: Cell culture, molecular cloning, basic pharmacology
Recommended expertise: Fluorescence microscopy, knowledge of receptor pharmacology, quantitative thinking
Key publications:
- Grushevskyi EO, Kukaj T, Schmauder R, Bock A, Zabel U, Schwabe T, Benndorf K, Lohse MJ (2019) Stepwise activation of a class C GPCR begins with millisecond dimer rearrangement. Proc. Natl. Acad. Sci. USA 116, 10150-10155
- Sungkaworn T, Jobin M-L, Burnecki K, Weron A, Lohse MJ, Calebiro D (2017) Single-molecule imaging reveals receptor-G protein interactions at cell surface hot spots. Nature 550, 543-54
- Nuber S, Zabel U, Lorenz K, Nuber A, Milligan G, Tobin AB, Lohse MJ, Hoffmann C (2016) β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle. Nature 531, 661-664
- Hlavackova V, Zabel U, Frankova D, Bätz J, Hoffmann C, Prezeau L, Pin J-P, Blahos J, Lohse MJ (2012) Sequential inter- and intra-subunit rearrangements during asymmetric activation of dimeric metabotropic glutamate receptor 1. Science Sign. 5, ra59
For more information:
Prof. Dr. Martin Lohse – martin.lohse@mdc-berlin.de
Application:
Contact details
Please contact us at:
info@oncornet.eu
ONCORNET Coordinator
VU University Amsterdam
The Netherlands
