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Archiv-Übersicht     Angebot Nr. 13094

Angebotsdatum: 24. Oktober 2018
Art der Stelle: Doktorarbeit
Fachgebiet: Biologie > Molekularbiologie
Titel des Themas: Hepatitis E virus trafficking in polarized human pluripotent stem cell-derived hepatocyte-like systems

Institut: Center for Integrative Infectious Diseases Research
Dr. rer. nat. Viet Loan Dao Thi
Im Neuenheimer Feld 344
69120 Heidelberg
Tel.:    Fax.:
Bundesland: Baden-Württemberg
Homepage: http://https://www.klinikum.uni-heidelberg.de/Dao-Thi.143655.0.html
E-Mail Kontakt: mail

Beschreibung: Hepatitis E virus (HEV) is the major cause of acute hepatitis in the world. Our lab uses stem cell technology to study HEV life cycle and HEV-host interaction. One particular aspect is HEV secretion, which is governed by its fecal-oral route transmission. The virus enters via the gastrointestinal tract and infects the liver, where it enters polarized hepatocytes from the bloodstream and exits with the bile to be shed into feces. We previously developed a novel differentiation protocol that allows columnar polarization of human embryonic or induced pluripotent stem cell (hESC/iPSC)-derived hepatocyte-like cells (HLCs) in transwells. Polarized HLCs can be infected with HEV on their basal side, with the majority of infectious virus being released to the apical compartment, recapitulating the directionality of infection occurring in vivo.
The successful applicant will combine this novel polarity system with genetic, biochemical, and imaging approaches to identify and characterize polarized trafficking and secretion routes of HEV. These efforts may help develop new strategies to block HEV assembly and secretion. Beyond virology, this work may lead to a better understanding of the fine-tuned spatio-temporal dynamics and regulation of the polarized trafficking machinery in hepatocytes.
For further questions, please contact: VietLoan.DaoThi@med.uni-heidelberg.de.
Methoden: A wide range of molecular and cell biological techniques with emphasis on live cell imaging using confocal microscopy; human tissue culture including embryonic and induced pluripotent stem cells and their differentiation to various cell types, mainly hepatocytes; 3D and complex co-culture systems; infection studies with human viruses in BSL2 and potentially BSL3 laboratories.
Anfangsdatum: 24. Oktober 2018
Geschätzte Dauer: 3 years