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Kurt-Mothes-Str. 3

06102

Halle (Saale)

Tel.+49 345 5524960

Fax:+49 345 5527387

sven.behrens@biochemtech.uni-halle.de

Prof. Dr. Sven-Erik Behrens

Die AG Behrens bearbeitet zwei Schwerpunkte:
1. Wir untersuchen die Rolle einzelner Proteine, die die Vermehrung verschiedener Viren in der Zelle beeinflussen. Bei den bearbeiteten Viren handelt es sich um Human-, Tier- und Pflanzenpathogene, denen aber einiges gemeinsam ist: Alle haben ein RNA (Ribonukleinsäure) Genom, und sie vermehren sich über grundlegend ähnliche Mechanismen. Die bekanntesten Viren sind das humane Hepatitis C Virus und das West-Nil Virus. Die untersuchten Proteine sind zelluläre Komponenten, die von diesen Viren 'rekrutiert' werden und bei deren Vermehrung 'helfen'. Zum anderen untersuchen wir Proteine, die, insbesondere im Zuge der pflanzlichen Immunantwort, eine virale Infektion erkennen und diese bekämpfen helfen.
2. In einem gemeinsamen Projekt mit der Kollegin Prof. Dr. Karin Breunig entwickeln wir Impfstoffe gegen Viren auf der Basis von Hefe. Näheres dazu auf
http://www.go-bio.de/lw_resource/datapool/_items/item_42/121109-go-bio_2012_preistraeger.pdf

Profil • Service

Vita

Curriculum vitae

Sven-Erik Behrens, Ph.D., Professor

Personal details

Date, place of birth 23rd February 1961,Clausthal-Zellerfeld, Germany
Citizenship German
Marital status married, 1 child

Address Springkrautweg 14; D-06120

Halle/Saale (priv.)
Martin-Luther-University, Halle-Wittenberg
Institute of Biotechnology; Deptm. Microbial
Biotechnology

Kurt-Mothes-Str. 3; D-06120

Halle/Saale

Tel./Fax D-345/5524960; D-345/5527378

Email Sven.Behrens@biochemtech.uni-halle.de
Web http://www.biochemtech.uni-halle.de/

Education

1980-1987

Studying Biology, Chemistry and Biochemistry at the Freie Universität Berlin

1987-1988

Degree research at the "Max-Planck-Institut (MPI) für molekulare Genetik Berlin (Prof. Wagner, Prof. Wittmann)
Subject of research "Characterization of functional elements of the rrnB operon of E.coli

1988

Diplom degree (M.Sc.) in Biochemistry at the
Freie Universität Berlin

1989-1992

Doctoral thesis research at the "Institut für Molekularbiologie und Tumorforschung (IMT) of the Philipps Universität Marburg (Prof. Lührmann)
Subject of research "Characterization of functional spliceosomal
UsnRNP-complexes from human cells

1992

Doctors degree (Dr. rer. nat.; Ph.D.) at the Freie Universität Berlin

Postgraduate experience, academic positions

1992-1993

Staff scientist at the "IMT of the Philipps Universität Marburg (Prof. Lührmann)

1993-1995

Postdoctoral associate at the "Istituto di Ricerche di Biologia Molecolare (IRBM) in Rome, Italy (Prof. De Francesco, Prof. Cortese).
Subject of research "Characterization of the RNA-dependent RNA polymerase of Hepatitis C virus (HCV)

1996-2002

Principal Investigator at the "Institut für Virologie (Prof. Thiel) of the Justus-Liebig-Universität (J-L-U) Giessen

1999

Post-doctoral lecture qualification (Habilitation) for Medical Virology at the J-L-U Giessen
Subject of research "Replication of Pestiviruses and HCV

2002-2005

Member (Associate Professor) at the Fox Chase Cancer Center, Philadelphia, USA

since 2005

Professor (W3/C4) at the Martin-Luther-Universität Halle-Wittenberg, Institut für Biochemie und Biotechnologie, Abt. Mikrobielle Biotechnologie. Naturwissenschaftliche Fakultät I
Subject of research "Replication and pathogenesis of HCV and related viruses

Honors and awards

1988

Diplom degree with "magna cum laude

1992

Ph.D. degree with "summa cum laude

1993-1998

Fellowship of the "Stipendiumprogramm Infektions-forschung awarded from the BMBF (German ministery for education and research)
Subject of research "Molecular determinants of the replication of HCV and the HCV-related pestiviruses

1999

"Privatdozent, PD at the J-L-U Giessen (Faculty of Medicine)

Expertenprofil

Summary of Research and current Research program

Prof. Dr. Sven-Erik Behrens

"Replication and pathogenesis of hepatitis C virus and related viruses

Worldwide, about 200 million people are infected with the hepatitis C virus (HCV). In ca. 85% of the patients the infection becomes persistent and often culminates to chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). In many countries hepatitis C is the leading cause for liver transplantations, and this situation is expected to considerably aggravate in the next 20 years. Moreover, HCV infections are associated with a number of extra-hepatic diseases such as mixed cryoglobulinemia and glomerulonephritis. An important issue along the way to develop urgently needed novel antiviral therapies and vaccines is to gain further insights into the molecular mechanisms that govern the HCV life cycle and that are responsible for the persistency of HCV infections.

In the last ca. 10 years, studies performed in my laboratory, several of which were performed with bovine viral diarrhea virus (BVDV) as a model system for HCV, led to important new insights into the function of virus-encoded and host-encoded factors during the viral replication process. About four years ago we initiated to explore novel types of vaccination procedures; more recently, we started investigating potential mechanisms of viral pathogenesis and persistence. Several of these accomplishments have been patented and some of them are currently applied for the development of novel antiviral substances and vaccines. Our work was/is supported by the DFG, the BMBF, the Fonds der chemischen Industrie (Germany), the NIH, the state of Pennsylvania (US) and several pharmaceutical companies (see Curriculum vitae).

1. As an initial effort in our HCV program, we identified the nonstructural protein 5B (NS5B) as the RNA-dependent RNA polymerase (RdRp) of HCV (EMBO J. 15: 12-22). NS5B is currently explored by major pharmaceutical companies as one of the most promising targets for antiviral approaches. Following a break of several years, NS5B turned back into the focus of our interest; currently, we explore the conditions that enable this important enzyme for a specific initiation of viral RNA synthesis.

2. The second major achievement concerned the development and characterization of a subgenomic RNA replicon system of the closely HCV-related pestivirus BVDV (Bovine viral diarrhea virus; J.Virol. 72: 2364-72). This discovery paved the way for the subsequent construction of a similarly organized HCV replicon by Prof. Bartenschlager and colleagues. Until 2005, the HCV replicon remained the only available experimental system that allowed functional studies of HCV replication in cell culture. We apply the considerably more robust BVDV system, often in direct comparison with the HCV replicon, to characterize the role of viral proteins and to analyze the structure and function of individual replication- and translation signals encoded by the viral RNA (see, for example: J.Virol. 73: 3638-48; J.Virol. 74: 5825-35; J.Virol. 75: 7791-7802; J.Virol. 77: 5352-59; Virology 333: 349-66).

3. In collaboration with Dr. Rehermann at the National Institute of Health (NIDDK, Bethesda) we currently evaluate BVDV replicons that express foreign antigens for a potential use as T-cell inducing/tolerance-breaking RNA vaccines. Expressing the HCV NS3 protein as a T-cell antigen in dendritic cells, we obtained encouraging data in mouse which suggest that BVDV replicons may be applied as therapeutic vaccines for the treatment of chronic HCV (Immunity 20: 47-58). We will next apply the BVDV replicon/dendritic cell approach to try to break the immune-tolerance to antigens of other microbial pathogens and tumor-associated antigens. Moreover, we evaluate novel types of procedures that should allow a straight-forward application of RNA vaccines in the clinics.

4. Another important discovery of our laboratory concerns the fact that members of the so-called "NF/NFAR group of proteins are involved in the replication process of BVDV and HCV. Specifically, the cellular proteins were shown to mediate a circular conformation of the viral genome, which is important for the regulation of translation and replication of the viral RNA genomes (EMBO J. 22: 5655-5665; RNA 10: 1637-52; RNA13 in press). Some NF/NFAR-proteins encode double-strand RNA-binding motifs (dsRBM) and thus belong to a protein family many members are in the current focus of interest due to their emerging roles in RNA metabolism (prominent examples are the RNA-dependent RNA kinase PKR, and the RNase III-like proteins Dicer and Drosha). Several lines of evidence suggest that the NF/NFAR-proteins, which in naïve cells are mainly nuclear, regulate gene expression on the transcriptional and post-transcriptional level and that the proteins are involved in the nuclear export of RNA. For example, the prototype NF/NFAR protein, NF90/NFAR-1 (DRBP76; ILF3) acts as an anti-decay factor of the mRNA of IL-2 and of urokinase plasminogen activator that are major players in immunity and inflammation. Moreover, NF90/NFAR-1 was shown to be part of the Exportin V complex involved in the nuclear export of small, helical RNAs. Finally, the entire protein group was indicated to be part of the so-called APOBEC complex in the cytoplasm and to be in a yet undefined manner part of the cellular response to a viral infection. Hence, a major focus of present work aims at a further biochemical characterization of the NF/NFAR proteins and at identifying cellular interaction partners that also participate in viral replication. Thus, we hope to understand how the interplay of these cellular factors with viral components supports viral replication and affects viral pathogenesis.

5. In a very recent project, we initiated investigating the replication process of an RNA plant virus, namely the Tombusvirus TBSV, which resembles HCV in several aspects. The replication of TBSV is particularly robust and occurs even in yeast cells. Using cytoplasmic extracts of plant host cells, we were recently able to establish an in vitro translation/replication system with TBSV RNA, which will allow us to characterize the function of host factors by depletion/complementation studies. Thus, we hope to gain important information on plant homologues of the NF/NFAR proteins and to apply experience obtained with this system to HCV, where in vitro replication is not yet conceivable.

Serviceangebot

Gezieltes Screening von Inhibitoren gegen verschiedene Mitglieder der Flaviviridae Familie wie HCV, BVDV, West-Nil. Erstellung von Gutachten zu neuen Diagnoseverfahren, Vakzinierungsverfahren und Screeningverfahren antiviraler Substanzen gerichtet gegen RNA Viren. Expertise bei der Entwicklung neuer Vakzinierungsverfahren. Expertise mit Pflanzenviren.

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