PhD position “Inhibition of innate immune receptors by Kaposi`s

EXCELLENT MEDICINE IN HANNOVER
Hannover Medical School
PhD position “Inhibition of innate immune
receptors by Kaposi‘s sarcoma associated
herpes virus”
A PhD position is available at the Institute for Biophysical Chemistry in the group of Dr. Susanne
Eschenburg at Hannover Medical School (MHH), Hannover, Germany in collaboration with Prof. Dr.
Thomas Schulz, Head of the Institute for Virology.
FIELD OF WORK
Aim of the project is to structurally and functionally characterize the interaction between a protein of
Kaposi‘s sarcoma associated herpes virus (KSHV) and members of the Nod-like receptor (NLR) family
of innate immunity receptors. The tumor virus KSHV is the causative agent of Kaposi’s sarcoma, a skin
cancer that is, amongst others, occurring in patients with AIDS or under immunosuppression. NLR
proteins are activated by pathogen-derived molecular patterns (PAMPs) to form signaling platforms,
so-called inflammasomes, which elicit inflammatory responses in the form of chemokine production.
The project is based on the observation that Orf63 of KSHV is able to directly inhibit inflammatory
signaling by the NLR proteins NLRP1 and NOD2, causing an attenuation of the inflammatory response.
Inhibition of Orf63 expression results in enhanced chemokine production and compromises viral replication. However, the molecular mechanism of Orf63’s inhibitory action is unknown and no structural
data are available. The interdisciplinary project will integrate a variety of different techniques from
protein biochemistry, X-crystallography, virology, cell biology and bioinformatics.
YOUR PROFILE
We are looking for talented individuals that are highly motivated to work in an interdisciplinary
research environment. Applicants (m/w) should hold an MSc degree in biochemistry, biophysics, virology or a related area. Previous experience in protein biochemistry, X-ray crystallography or virology
is required. Fluency in written and spoken English is expected.
OUR OFFER
The Institute for Biophysical Chemistry and the Institute for Virology offer an exceptional research
environment for the proposed studies including state-of-the-art research facilities and technologies.
Work should commence at the earliest possible date. The successful candidate (m/f) will be funded via
a stipend of the Infection Biology cooperation COALITION (Communities allied in Infection) at MHH
in the amount of e 1500 per month. The position is available for a period of three years.
HOW TO APPLY
Please send your application by electronic mail and preferably in one single PDF-document to
[email protected]. For full consideration, the application should include a cover
letter, a detailed CV, copies of all educational certificates and transcripts of records, a summary of
previous research, and two letters of recommendation. The deadline for applications is November
15th, 2016. Early applications are encouraged. MHH is an equal opportunity employer. Qualified women are therefore particularly encouraged to apply. Applicants with disabilities are treated with preference given comparable qualification.
Medizinische Hochschule Hannover
Dr. Susanne Eschenburg, Institut für Biophysikalische Chemie
Carl-Neuberg-Str. 1, Gebäude J4, Ebene S0, Raum 1040, D-30625 Hannover
Tel.: +49 (0) 511 5328655
Website: https://www.mh-hannover.de/34329.html
RELATED REFERENCES
1. S.M. Gregory, B.K. Davis, J.A. West, D.J. Taxman, S. Matsuzawa, J.C. Reed, J.P. Ting, and B. Damania.
(2011) Discovery of a viral NLR homolog that inhibits the inflammasome. Science 331, 330-334.
2. J.P. Boyle and T.P. Monie. (2012) Computational analysis predicts the Kaposi‘s sarcoma-associated
herpesvirus tegument protein ORF63 to be alpha helical. Proteins 80, 2063-2070.
3. T.F. Reubold, G. Hahne, S. Wohlgemuth, and S. Eschenburg. (2014) Crystal structure of the leucinerich repeat domain of the NOD-like receptor NLRP1: implications for binding of
muramyl dipeptide. FEBS Lett 588, 3327-3332.
4. G. Zhang, B. Chan, N. Samarina, B. Abere, M. Weidner-Glunde, A. Buch, A. Pich,
M.M. Brinkmann , and T.F. Schulz. (2016) Cytoplasmic isoforms of Kaposi Sarcoma
Herpesvirus LANA recruit and antagonize the innate immune sensor cGAS. Proc Natl
Acad Sci U S A. 113, E1034-1043.
www.mh-hannover.de

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