Ruprecht-Karls-Universität Heidelberg
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Thi0118 - Scientist (f/m) / PhD position
Project no:
Thi0118

Project leader:

Project supervisor:
Thi, Viet Loan Dao
Application deadline:
31. Jul 2018
Start of PhD project:
15. Aug 2018

Project description:

Title:
Hepatitis E virus trafficking in polarized human pluripotent stem cell-derived hepatocyte-like systems
Summary:
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: vdaothi@rockefeller.edu.
References:
1. Wu X*, Dao Thi VL*, Liu P, Takacs CN, Xiang K, Andrus L, Gouttenoire J, Moradpour D, and Rice CM. Pan-Genotype Hepatitis E Virus Replication in Stem Cell-Derived Hepatocellular Systems. In press at Gastroenterology.

2. Takacs CN, Andreo U, Dao Thi VL, Wu X, Gleason CE, Itano MS, Spitz G, Belote RL, Flatley BR, Scull MA, Rice CM, and Simon SM. 2017. Differential regulation of lipoprotein and hepatitis C virus secretion by Rab1b. Cell Rep. 21(2):431-441.
Methods that will be used:
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.
Cooperation partners:
Personal qualifications:
We are looking for a highly motivated, interactive and team-oriented candidate with a background and interest in molecular biology and virology. Applicants should hold a Master’s degree in Biomedical or Molecular Sciences, Biochemistry, Biology or related fields. Expertise in cell imaging and confocal microscopy is advantageous.
Keywords:
Molecular virology, stem cells, cellular polarization, trafficking