DEA D - Spiral

Offre de stage de Master / Master Internship offer (2014/15)
Tuteur du stage et Laboratoire d’accueil / Internship supervisor and Host laboratory:
Supervisor
Birke BARTOSCH ([email protected], 0472681975)
Laboratory:
Centre
de
Recherche
en
Cancerologie
de
Lyon
(CRCL)
Team 15: Mechanisms of chronic hepatitis B and C pathogenesis and novel antiviral
strategies;
UMR Inserm U1052/CNRS 5286
Titre du projet de recherche / Research project title:
Role of metabolic changes in hepatitis C virus-induced liver disease
Description du projet / Project description:
Metabolic dysfunctions, and particularly obesity and diabetes have become a major
pandemic health problem and lead frequently to non-alcoholic fatty liver disease or steatohepatitis (NAFLD/NASH) and liver cancer. Hepatocellular carcinoma (HCC) is the fifth
most common and third deadliest cancer and remains extremely difficult to treat. We are
using hepatitis C virus (HCV) as a tool to understand the role of metabolic dysfunctions in
liver disease and cancer. Indeed, just like in NAFLD/NASH, chronic hepatitis C patients
are frequently diagnosed with insulin resistance/diabetes and fatty liver. Insulin resistance
and fatty liver are known to be induced by HCV directly and to trigger liver disease
progression due to their close links with oxidative stress and inflammatory processes. We
are analyzing on the molecular level how HCV alters metabolic fluxes and induces insulin
resistance. We are furthermore investigating whether these metabolic alterations are
required for viral replication and what
roles they play in liver disease and
cancer. The aim of these studies is to
develop novel treatment approaches
with dual function; approaches that can
block viral replication and block disease
progression by restoring metabolic
functions. The master project will focus
in particular on HCV-induced changes to
the
hexosamine
pathway
and
glutaminolysis. As these pathways are
known to be frequently altered in tumor
cells, these HCV-induced metabolic
alterations may form an important
predisposition towards liver cancer.
Methodology:
Virology (infection assays at P2 / P3 level)
Cell and molecular biology (cloning, PCR, Western, RTqPCR, IF)
Metabolics (Biochemistry and NMR, GC-MS in collaboration with platforms)
Candidate:
We are looking for a highly motivated candidate, interested in the fields of
metabolics/cancer and virology who is looking for a host-laboratory to perform his PhD.
The candidate should be able to speak (or at least read) English and be happy to work in
a team. To allow for P2/P3 safety level work the candidate needs to be vaccinated
(seroprotected) against HBV. Experience in tissue culture and virology would be a plus.
Publications du laboratoire (5 max) / Lab publications (5 max):
1) Fages A, Pontoizeau C, Jobard E, Lévy P, Bartosch B, Elena-Herrmann B. Batch Profiling Calibration for Robust
NMR Metabonomic Data Analysis. 2013, Analytical and Bioanalytical Chemistry, in press.
2) Clément S, Fauvelle C, Branche E, Kaddai V, Conzelmann S, Boldanova T, Bartosch B, Minehira K, and Negro F.
Role of Seipin in lipid droplet morphology and Hepatitis C virus life cycle. 2013, Jounral of General Virology, in
press
3) Charlène Brault, Pierre L. Levy and Birke Bartosch. Hepatitis C virus-induced mitochondrial dysfunctions. 2013
Viruses, in press.
4) Baptiste Jammart, Maud Michelet, Eve-Isabelle Pécheur, Romain Parent, Birke Bartosch, Fabien Zoulim, and
David Durantel. VLDL-producing and HCV-replicating HepG2 cells secrete apoE hybrid viral particles. 2013,
Journal of Virology, in press.
5) Birke Bartosch. Hepatitis C virus and its complex interplay with the hepatic glucose and lipid metabolism. 2009
Journal of Hepatology, 50(5):845-7.