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Project proposal for 6 to 9 month internship We are looking for one enthusiastic and interested master student. If you want to know more information or apply, please do not hesitate to contact us by email. Affiliation: Virology Division of the Department Infectious Disease and Immunology at the Faculty of Veterinary Medicine, Utrecht University Our general aim is to understand the infection process of viruses at the level of the cell, the organism and the population, and the development of strategies for the diagnosis of and protection against these infections. With respect to the viruses, we focus on enveloped positive stranded RNA viruses with particular attention to coronaviruses and baculoviruses. Speicial focus of the Berend Jan Bosch is the targeting and cell entry of coronaviruses and baculoviruses. Schedule Starting Mid September to October 2012 Supervisor Dr. Berend Jan Bosch - [email protected] Daily Supervisor: Oliver Wicht – [email protected] Molecular determinants for protease dependence of porcine epidemic diarrhea virus (PEDV) The propagation of the swine Coronavirus PEDV field strains in cell culture is dependent on protease activity. The main determinant for tropism and viral entry is the spike fusion protein. We have created several mutant viruses that allow is to characterize and investigate the responsible amino acids within the spike protein. A deeper understanding of the viral entry mechanisms will allow us to improve the virus production for vaccine purposes. Within this project, the student will characterize and study the PEDV-Spike protein by i) classical virological methods ii) protein biochemistry iii) molecular biology. Alternative Project: Dimerization of the receptor for Murine Hepatitis Virus (MHV) Pilot experiments are performed at the moment; this project depends on the outcome. MHV infects mouse cells in cell culture by using mCeacam1a as receptor. It remains unclear how the receptor mediates virus uptake by endocytosis and virus-cell fusion. Intracellular signaling of the receptor does not play a role. Instead, the virus might induce dimerization of the receptor and thereby inducing endocytosis and uptake. Within this project, the student will perform mutagenesis study on the transmembrane domain of the receptor to determine the molecular requirements for receptor mediated virus infection by i) classical virological methods and ii) molecular biology. _____________________________________________ Oliver Wicht, MSc. Department Infectious Diseases & Immunology, Division Virology Utrecht University, Faculty of Veterinary Medicine Yalelaan 1 3584 CL Utrecht The Netherlands tel: +31 (0)30 253 5094 fax: +31 (0)30 253 6723 e-mail: [email protected]