Hepatitis C virus (HCV) is an important human pathogen that causes chronic liver diseases in millions of infected people worldwide. HCV is an enveloped single-stranded RNA virus that infects predominantly hepatic cells. The process of viral entry into the host cells is an obvious target for virus inhibition, however the exact mechanism of this event is not known. It is established that the two HCV envelope glycoproteins E1 and E2 are involved. The ectodomain of E2 interacts with high affinity with human CD 81, the best characterised cellular receptor of HCV.The interaction between E2 and CD81 is also involved in immunomodulation during the HCV infection. E2 also forms heterodimers with E1 on the viral surface. The aim of the proposed project is to apply rec ently developed techniques for the expression of glycoprotein ectodomains in order to provide structural information on the ectodomain of HCV envelope glycoprotein E2 and its interactions with the cellular receptor CD81 and HCV glycoprotein E1. The structure of E2 and its complexes with CD81 and E1 will provide a better understanding of the function of HCV envelope glycoproteins in cell surface recognition and membrane fusion and thus HCV pathogenesis. Structural information on E2 may also be exploited for developing new drugs targeting this human pathogen.Working on the proposed project, I will obtain experience in numerous new techniques, including e.g. protein expression in mammalian and insect cells and mass spectrometry as well as advance my knowledge of protein crystallography. I will also use local high-throughput platforms and robotics. This will allow me in the future to work independently on complex projects at the interface of biology and biophysics.