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Ph.D. (fulltime) VU University Medical Center, Amsterdam, The Netherlands Job description The goal of this project is to identify the genes responsible for depression, making use of genome-wide association data. You will be trained in finemapping, resequencing high priority candidate genes, bioinformatic analysis for biologically relevant variants, functional analysis of high priority variants. You will be responsible for the generation of reliable data on this project. In addition you will investigate patients with depression from NESDA cohort (see www.nesda.nl) by 1) performing a genome-wide expression analysis 2) collecting and isolating RNA from a two-year follow-up 3) validate relevant gene expression data and candidate RNA’s, that are differentially expressed at baseline collection and after two years. You will be supervised on a daily basis by a postdoc and by the research team, including e.g. statistician, a geneticist, a psychiatrists, a data manager and a genetical epidemiologist. Requirements - Master degree in (Bio)medical Science, (medical) Biology, degree in medicine or related background Interest and preferably experience in genetic, statistical, bioinformatics, molecular and cell biological techniques Ability to work in a multidisciplinary team Candidate needs to be ambitious and innovative Organization The Section Medical Genomics, Department of Clinical Genetics and the Department of Psychiatry (VUMC) are part of the Center for Neurogenomics and Cognitive Research-VU, in which research focuses on depression and cognition. http://www.cncr.nl/ Condition of employment You will work as a team member of TI Pharma project. This is one of the projects under the TI Pharma initiative to bring together university and industry. The partners on the project are Organon, University Medical Center Utrecht, VU and VU University Medical Center Amsterdam. Duration of the contract:4 years. You will enrol in the PhD graduate programs of the TiPharma institute, the CNCR and the Graduate school for Neuroscience Amsterdam. Furthermore you will attend a unique drug discovery education and training program offered by TI Pharma. Additional information According to the WHO, depression will be the second leading cause of disability worldwide by 2020 and costs over $43 billion/year in the US alone. In the Priority Medicine program the large gap between treatments needs availability is especially underscored for psychiatric disorders, such as mood disorders and psychosis. The efficacy of currently available anti- depressants ranges from conservative estimates of 35% to more optimistic estimates of 60%. This is primarily caused by a lack of proper diagnosis of patients resulting in ill-defined treatment strategies but also the lack of proper assessment of novel treatment approaches during preclinical and clinical drug development by the pharmaceutical industry. Diagnostic accuracy and prediction of treatment-outcome is limited by subjective phenotypic assessments and would strongly benefit from psychometric and biological, so called endophenotypes, in combination with genetical assessments. The endophenotype that is most proximal and direct to the genotype in gene expression. Therefore for the prediction of pharmaco-treatment outcome, and testing drug efficacy in the clinical phase, there is a great need to apply pharmacogenomics technologies including genetics, genome-wide expression studies. This way, we aim to improve the classification of patient groups for better evaluation of randomized trials and allowing for more focussed clinical trials leading to improved medications in mood disorder and psychosis. Area of research of this project is identification of the possible candidate regions involved in depression and subsequently the biological important variants. The starting point will be the results of the whole genome association study funded through the GAIN initiative. Through this initiative the results of GWA study on ~1860 patients and matched controls from the twin register of Netherlands. For these regions we will perform the detailed fine-mapping. While the results from the GAIN study may identify specific candidate variants (from known SNPs) for functional assays to be followed up directly, it is much more likely that they will identify regions showing evidence for association with disease, but not the relevant functional variant per se. Therefore we will conduct in depth genotyping of these regions for association and haplotype analysis , investigate the possible biological relevance of these variants in more detail and conduct both in vitro and in vivo functional assays of the variants. The other part of the project is performing a genome-wide expression analysis which can be used to identify subgroups ad inter-individual differences in disease and response to a given treatment. Application You can apply by sending your application to: Dr. Marianna Bevova VU University Medical Center, Amsterdam [email protected] Tel:+31-20-5983854 Deadline for applications is 30.11.08