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Project description
Genome-wide association studies (GWAS) have so far identified hundreds of genetic loci that are robustly associated with cardiometabolic risk factors and diseases, such as obesity, type 2 diabetes, atherosclerosis and coronary artery disease. With few exceptions, the causal genes in these loci are currently unknown. Before results from GWAS can be translated to something that can be used in the clinic - for example as novel biomarkers or drugs - we need to identify and characterize the causal genes in these loci. Recent developments in CRISPR-Cas9-based mutagenesis, high-throughput imaging, and image-based analyses have highlighted the zebrafish as a promising model system for large-scale genetic screens.

The overall aim of the proposed project is to identify causal genes in GWAS-identified loci for cardiometabolic risk factors and diseases using zebrafish model systems.

The planned projects includes the following parts: 1) Identifying potentially causal genes for obesity, type 2 diabetes, atherosclerosis and coronary artery disease by means of high-throughput, image and lab-based genetic screens in mutant and wildtype zebrafish larvae; 2) experimental follow-up of mutants that show promising results in the primary genetic screens using more detailed phenotypic analyses in adult fish; 3) Back-translation of findings in zebrafish to establish the relevance for humans using available cohort studies, such as ULSAM, PIVUS, TwinGene and EpiHealth.

The PhD student(s) will assist in generating mutant models using CRISPR-Cas9, maintain the lines, generate and prepare larvae and fish for experiments, phenotype the larvae using high-throughput microscopy and other methods, prepare samples for biochemical analysis, perform histological and immunohistochemical experiments, perform data analysis, and disseminate results in manuscripts. The student(s) will receive a thorough education in molecular biology, zebrafish husbandry, imaging, epidemiology and handling of large datasets. The PhD student(s) will be placed in the Ingelsson research group (www.ingelsson.org). The ERC, VR and Wallenberg Academy Fellow program fund the projects.

Requirements of the applicant
Applications are accepted from highly motivated candidates with a master degree in Biomedicine, (Molecular) Medicine, Molecular (Cell) Biology or similar. Written and oral proficiency in English is a prerequisite, as are basic knowledge of, and skills in molecular biology. Prior knowledge of epidemiology, bioinformatics and/or programming is a bonus. Personal qualities will be considered in the ranking of candidates.

The application should include a statement of research interest, a CV/resume, a verified list of course grades and contact details for reference persons. If available, a Master thesis (completed or in draft form) and letters of recommendation can also be included.

Local salary rules will apply.

The rules governing this process can be found (in Swedish) in Högskoleförordningen 5 Chapter 1-7 §§ and in University rules http://regler.uu.se/.

For more information, please contact:
Marcel den Hoed, PhD, phone +46-70-425 07 52, marcel.den_hoed@medsci.uu.se,
Erik Ingelsson, Prof, phone +46-70-756 94 22, erik.ingelsson@medsci.uu.se, or
Anna Foyer, staff coordinator, phone +46-18-611 43 92, anna.foyer@medsci.uu.se.

You are welcome to submit your application no later than October 20th, 2014,
UFV-PA 2014/2745. Please use the link below to access the application form.

2 PhD position in Medical Science – Functional genomics of cardiometabolic risk factors and diseases using zebrafish model systems
We decline offers of recruitment and advertising help. We only accept the application the way described in the advertisement.
Placement: Department of Medical Sciences
Type of employment: Full time , PhD placement
Pay: Fast lön
Number of positions: 2
Working hours: 100%
Town: Uppsala
County: Uppsala län
Country: Sweden
Union representative: Carin Söderhäll, TCO/ST 018-471 1997 1
Per Sundman, Saco-rådet 018-471 1485 1
Stefan Djurström, Seko 018-471 3315 1
Number of reference: UFV-PA 2014/2745
Last application date: 2014-10-20
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