Ruprecht-Karls-Universität Heidelberg
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Mueller0119 - Scientist (f/m) / PhD position
Project no:
Mueller0119

Project leader:

Project supervisor:
Müller, Barbara
Application deadline:
10. May 2019
Start of PhD project:
1. Jun 2019

Project description:

Title:
Imaging analysis of dynamic events in HIV-1 cell interaction
Summary:
The Department of Infectious Diseases, Virology at the University Hospital Heidelberg, Germany offers a position for a PhD student working on Dynamics of HIV-1 post-entry events in the group of 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 group applies advanced imaging techniques to study dynamic events in HIV-1 assembly at the plasma membrane and in early post-entry stages of HIV-1 replication. In this project, we specifically focus on HIV-1 cell-cell transmission and post-entry stages of HIV-1 replication with a focus on dynamic aspects. 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. For their investigation, we establish and apply a variety of state of the art fluorescence labeling technologies and live-cell imaging, complemented by novel biochemical approaches.

We offer an interesting, interdisciplinary research topic with biomedical relevance in an interactive scientific environment, including collaborations with national and international partners, at an internationally competitive level. The lab is located in the newly opened Center for Integrative Infectious Disease Research which also houses a state-of-the-art imaging platform on the Heidelberg campus. 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:
Bejarano et al. (2019) HIV-1 nuclear import in macrophages is regulated by CPSF6-capsid interactions at the Nuclear Pore Complex. Elife 8. pii: e41800. doi: 10.7554/eLife.41800

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

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

Eckhardt et al. (2011) A SNAP-tagged derivative of HIV-1--a versatile tool to study virus-cell interactions. PLoS One. 2011;6(7):e22007. doi: 10.1371/journal.pone.0022007. Epub 2011 Jul 22.

Reviews:
Müller et al. (2019). A Spotlight on Viruses - Application of Click Chemistry to Visualize Virus-Cell Interactions. Molecules ;24(3). pii: E481. doi: 10.3390/molecules24030481

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 and advanced light microscopy imaging techniques. Microscopic analyses are complemented by a wide range of virological (particle preparation, infectivity measurements), cell biological and biochemical methods.
Cooperation partners:
Hans-Georg Kräusslich and Oliver Fackler (CIID Heicelberg, Virology); Kai Johnsson (MPImF Heidelberg, Germany; chemical biology); Martin Beck (EMBL Heidelberg, Germany; 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 motivated 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 labeling, live cell imaging, virus entry, cell-cell transmission, intracellular transport, nuclear import