Ruprecht-Karls-Universit├Ąt Heidelberg
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Sinning0119 - Scientist (f/m) / PhD position
Project no:

Project leader:

Project supervisor:
Sinning, Irmgard
Application deadline:
15. Apr 2019
Start of PhD project:
1. May 2019

Project description:

The signal recognition particle in health and disease
Research in our group centers around cotranslational processes that occur at the ribosomal tunnel exit. Here, a rather larger number of proteins and complexes comprising chaperones, enzymes and targeting factors seem to compete for access to the nascent chain. The human signal recognition particle (SRP) machinery involved in protein targeting to the ER is one of our targets. We want to understand the molecular mechanisms of a number of severe diseases that are linked to SRP malfunction. Having recently been able to reconstitute the whole human SRP, we have overcome a severe bottleneck that prevented detailed mechanistic studies of hSRP. Now we combine an integrated structural biology approach (using X-ray crystallography, cryo-EM, SAXS and NMR) with in vivo and in vitro analyses of hSRP components and their function. Our work is interdisciplinary and will allow the talented PhD student to gain expertise in a broad range of structural, biophysical and biochemical methods. At the end, we will obtain mechanistic insights into the workings of a universally conserved targeting system and its role in health and disease.
1. Wild, K., D. Juaire et al. & Sinning, I. (2019) Reconstitution of the human SRP system and quantitative and systematic analysis of its ribosome interactions, Nucl. Acids Res. 2019 Jan 15. doi: 10.1093/nar/ gky1324.

2. Becker, M.M.M., Lapouge, K., Segnitz, B., Wild, K. & Sinning, I. (2017) Structures of human SRP72 reveal its function in co-translational protein targeting, Nucl. Acids Res. 45: 470-481.

3. Grotwinkel, J.T., Wild, K., Segnitz, B. & Sinning, I. (2014) SRP RNA remodeling by SRP68 explains its role in protein translocation, Science 344: 101-104.
Methods that will be used:
Integrated structural biology: X-ray crystallography, cryo-EM, SAXS and NMR, as well as in vivo and in vitro analyses using biochemical and biophysical techniques, protein expression and purification, protein-protein interactions, targeting and insertion assays.
Cooperation partners:
Raphael Carapito, Strasbourg
Personal qualifications:
The candidate should have a strong background in biochemistry/biophysics with a specific interest in structural biology. The candidate should be highly motivated to succeed in science. Experience in protein expression and purification would be an advantage.