Ruprecht-Karls-Universität Heidelberg
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Ruggieri0118 - Scientist (f/m) / PhD position
Project no:

Project leader:

Project supervisor:
Ruggieri, Alessia
Application deadline:
30. Sep 2018
Start of PhD project:
1. Nov 2018

Project description:

Physiological relevance and biophysical properties of stress granule oscillations
Stress granules (SGs) are cytosolic aggregates of stalled translation pre-initiation complexes that form by phase transition under various stress conditions, including virus infection. SGs participate in controlling protein synthesis and are generally thought to have a cytoprotective function. Previously, we have shown that infection with the major human pathogen hepatitis C virus (HCV) induces an oscillating host cell stress response characterized by cycles of SG assembly and disassembly. The current project investigates two aspects of SG biology.
The first part aims at determining the biological function of SG oscillations in the course of HCV infection in physiologically relevant systems. The successful candidate will establish cell culture systems such as polarized hepatoma organoids and human stem cell-derived hepatocyte cultures to study SG dynamics using long-term live-cell imaging and light-sheet microscopy.
The second part aims at reconstituting SG dynamics in vitro. SG assembly and disassembly are multistep processes that remain poorly understood. Taking advantage of the biophysics expertise of our local collaborators, the applicant will use a new bottom-up synthetic biology method to generate chemically stable cell-like compartments called “droplet stabilized giant unilamellar vesicles”. These lipid-based compartments will be used to reconstitute the cellular stress response and study the minimal requirements of the SG assembly process. Depending on the specific background the successful candidate will work on one or both parts, respectively.
Ruggieri, A. et al. Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection. Cell Host Microbe 12:71-85 (2012).
Methods that will be used:
Molecular biology and biochemistry techniques, virology techniques, tissue engineering and three-dimensional cell culture systems, live-cell microscopy, light-sheet microscopy, image analysis.
Cooperation partners:
The project is embedded within the SFB1129 “Integrative Analysis of Pathogen Replication and Spread“, funded by the DFG.
Personal qualifications:
Applicants should hold a Master degree in Biotechnology, Biochemistry, Molecular Biology or Molecular Sciences. We are looking for a highly motivated, interactive and team-oriented candidate with a strong background in molecular biology. Expertise in tissue engineering is advantageous.

Applications should be submitted to the following e-mail address: Only complete applications will be considered:
- Detailed curriculum vitae
- Motivation letter
- Description of research experience including applied methodologies
- List of two references with complete contact details (including Master thesis supervisor)