Unraveling the molecular mechanism of Hepatitis C virus assembly

PI: Salvatore Chiantia, Emanuel Schneck || Requires: Biophysics or related degree
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Hepatitis C virus (HCV) is a significant threat to human health worldwide. It is estimated in fact that between 2 to 5 % of the human population is infected by HCV. Despite the significant public health burden, there is yet no vaccination available and the existing therapies have extremely high costs. Despite the continuous scientific progress in the field of HCV pathology, the development of alternative therapeutic approaches is hindered by the lack of basic understanding about the molecular mechanisms involved in the viral life cycle, e.g. during the assembly of new virions in infected cells.
In this context, we propose to use a recently developed in vitro lipid monolayer system, as an advanced model of cellular structures in which the first step of virus assembly occurs. By combining this biophysical model with ellipsometry, x-ray/neutron reflectometry, and fluorescence microscopy methods, we will quantitatively characterize the adsorption and oligomerization of the HCV capsid protein and its interaction with lipid droplets (LDs). More in detail, using approaches such as Fluorescence Correlation Spectroscopy, Number&Brightness and Image (Cross) Correlation, we will monitor protein-lipid and protein-protein interactions driving the capsid protein oligomerization, under well-defined and controlled conditions. The investigation will be further complemented by analogous measurements in living cells.
The results of our study will help to better understand the life cycle of HCV and, specifically, virus assembly, thus providing the opportunity to identify new targets for alternative therapeutic approaches.

Master in Biophysics or related subject. Profound practical knowledge in molecular biology (e.g. cloning, mutagenesis) and cellular biology, with focus on protein-lipid interaction. Experience with programming (e.g. Matlab) and fluorescence microscopy will be an advantage.
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