Ruprecht-Karls-Universität Heidelberg
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Mueller_Kraeusslich0218 - Scientist (f/m) / PhD position
Project no:
Mueller_Kraeusslich0218

Project leader:

Project supervisor:
Müller, Barbara
Kräusslich, Hans-Georg
Application deadline:
31. Jul 2018
Start of PhD project:
1. Sep 2018

Project description:

Title:
Imaging analysis of dynamic events in HIV-1 host-interaction
Summary:
The Department of Infectious Diseases, Virology at the University Hospital Heidelberg, Germany offers positions for PhD students working on Lipid-protein interactions in HIV-1 assembly, on High resolution analysis of early HIV-1 replication or on Dynamics of HIV-1 post-entry events in the groups of Prof. Dr. Hans-Georg Kräusslich and Prof. Dr. Barbara Müller.

The interaction of human immunodeficiency virus with its host cell involves numerous highly dynamic steps that are difficult or impossible to investigate by classical approaches. Therefore, our groups apply advanced imaging techniques to study dynamic events and structural details in HIV-1 assembly at the plasma membrane and in early post-entry stages of HIV-1 replication. In one project, we specifically focus on HIV-1 lipid-protein interactions at the plasma membrane, which are essential to form the specific lipid envelope of infectious HIV-1 particles and to stably recruit virion components to the assembly site. Other projects address post-entry stages of HIV-1 replication with a focus on either structural aspects applying super-resolution and correlative light- and electron microscopy or on dynamic aspects focusing on live cell imaging and novel labeling technologies. We investigate transport and uncoating of the viral capsid, reverse transcription of the viral genome and nuclear translocation of the resulting complex in different target cells. These processes are complex and require tight regulation in space and time; post-entry events are further influenced by numerous host cell restriction and dependency factors. There are many open questions (including surprisingly basic ones) for example “How are lipids and glycoproteins recruited to the HIV-1 assembly site?”, or “How are viral genomes shielded from DNA sensors and delivered to the nucleus?”.

We offer interesting, interdisciplinary research topics with biomedical relevance in an interactive scientific environment, including collaborations with national and international partners, at an internationally competitive level. The labs are located in the newly opened Center for Integrative Infectious Disease Research on the Heidelberg campus, which also houses a state-of-the-art imaging platform. Successful candidates have the possibility to apply for the HBIGS International Graduate School to fully benefit from the excellent scientific training of this program.
References:
Mücksch et al., (2017). Synchronized HIV assembly by tunable PIP2 changes reveals PIP2 requirement for stable Gag anchoring. Elife. 6. pii: e25287. doi: 10.7554/eLife.25287.

Sakin et al. (2017). A versatile tool for live-cell imaging and super-resolution nanoscopy studies of HIV-1 Env distribution and mobility. Cell Chem Biol. 24:635-645.e5

Mattei et al. (2016). The structure and flexibility of conical HIV-1 capsids determined within intact virions. Science. 2016 Dec 16;354(6318):1434-1437.

Hanne et al. (2016). Stimulated Emission Depletion Nanoscopy Reveals Time-Course of Human Immunodeficiency Virus Proteolytic Maturation. ACS Nano. 10(9):8215-22.

Peng et al. (2014) Quantitative microscopy of functional HIV post-entry complexes reveals association of replication with the viral capsid. eLife 2014 10.7554/eLife.04114

Muranyi et al. (2013) Super-resolution Microscopy Reveals Specific Recruitment of HIV-1 Envelope Proteins to Viral Assembly Sites dependent on the Envelope C-Terminal Tail. PLoS Pathog, 9: e1003198

Chojnacki et al. (2012). Maturation-dependent HIV-1 surface protein redistribution revealed by fluorescence nanoscopy. Science 338, 524-528.

Reviews:
Sakin et al. (2016). Labeling of virus components for advanced, quantitative image analyses FEBS L 590:1858-1876

Hanne et al. (2016) Super-resolved insights into human immunodeficiency virus biology. (2016) FEBS Lett. doi: 10.1002/1873-3468.12186


https://www.youtube.com/watch?v=IX8lnL4kMNQ
https://www.youtube.com/watch?v=GxDWwEvWC_A

Methods that will be used:
We apply a variety of fluorescence labeling methods (including genetic code expansion and click chemistry) and advanced light and electron microscopy imaging techniques with a focus on live-cell imaging and super-resolution microscopy. Microscopic analyses are complemented by a wide range of virological, cell biological and biochemical methods. Work with infectious virus under BSL3 conditions is possible, but not essential.
Cooperation partners:
John Briggs (Cambridge, UK; cryo-electron microscopy); Britta Brügger (BZH Heidelberg, lipidomics); Kai Johnsson (MPImF Heidelberg, Germany; chemical biology); Martin Beck (EMBL Heidelberg, Germany; cryo-EM and mass spectrometry); Jan Konvalinka (IOCHB, Prague, Czech Republic; chemistry); Don C. Lamb (LMU, Munich, Germany; biophysical methods); Edward Lemke (Mainz, Germany; chemical biology); Carsten Schultz (Oregon Health and Science University, USA; chemical biology).
Personal qualifications:
Applicants should have a Master degree (biology, biochemistry, possibly biophysics or molecular medicine). They should be interested in addressing basic virological questions using different methods with a very strong focus on imaging techniques. A good background in standard molecular biological methods is expected. Ideal candidates would already have some experience in fluorescence microscopy and image analysis, together with a background in cell biology, biochemistry or biophysics.
We are looking forward to meet curious and students who are enthusiastic about science. They should enjoy working independently, but also love to interact, discuss and collaborate with scientists from different disciplines and nations.
Keywords:
HIV-1, fluorescence imaging, correlative microscopy, live cell imaging, virus entry, virus assembly, lipid-protein interactions, nuclear import