Researcher in Translational Genomics of Environmental Adaptation

Researcher in Translational Genomics of Environmental Adaptation

Uppsala University

Uppsala, Sweden

Project description:

Understanding the relationship between genetic variation and phenotypic variation is a fundamental goal in genome biology and genomic medicine. In the last 15 years, genome-wide association studies (GWAS) have detected numerous DNA regions that are associated with complex traits in humans. Translation to functional understanding is lagging, in part because >95% of human GWAS-identified loci are in non-coding, regulatory regions of the genome, and pinpointing causal genes and mechanisms is complex. In this project, we aim to understand the molecular mechanisms of species’ ability to adapt to their environment. The herring is an excellent system to study such adaptations. First, herring fertilize their eggs externally, which exposes them to considerable environmental variability throughout their life cycle. Secondly, there are ~1012 herring on earth, which mate randomly. Hence, allele frequencies of gene variants in different locally adapted subpopulations are set by natural selection, while genetic noise (genetic drift) plays a minute role. GWAS in herring performed at Leif Andersson’s lab at Uppsala University have identified >100 genomic regions controlling adaptation to differences in salinity, temperature, timing of reproduction and light conditions. Unlike in humans, many associated DNA regions in herring include single base changes in protein coding sequence that clearly point to likely causal variants and genes. Funded by the Wallenberg Foundation and enabled by a new research infrastructure built by the BalticWaters Foundation, we now recruit a researcher to be part of a team striving to unravel the molecular mechanisms through which some identified variants influence species adaptation. The researcher will focus on base editing and functional experiments in zebrafish models, and possibly in herring as well. Throughout the project, the researcher will interact with experts in the fields of evolutional biology and spatial transcriptomics, who will approach the challenge from complimentary angles.

Work description:

The researcher will primarily study molecular mechanisms hypothesized to underly species adaptation by developing and using zebrafish models. Tasks include: 1) generating mutants using state of the art base editing and CRISPR/Cas9 approaches; 2) generating transgenic, fluorescent reporter lines for putative causal genes; 3) using in vivo fluorescence microscopy to visualize effects of variants; 4) preparing samples for downstream experiments and analyses, e.g. spatial and/or single cell RNA sequencing and other -omics approaches; 5) objectively quantifying image data; 6) data management, quality control, and statistical analysis of data; 7) staying up to date on methods development in the field and implementing important advances; 8) writing reports and presenting results to the team and at international meetings; and 9) disseminating results in manuscripts for publication in peer-reviewed journals.

Qualifications:

• Applications are accepted from highly motivated candidates with a PhD in Molecular Biology or similar, with at least three years of relevant research experience at post-doctoral level;
• Applicants must have a documented and broad competence in basic molecular biology methodology;
• Documented experience with genome engineering in zebrafish is required;
• Applicants must have at least 2 years of experience using zebrafish as a research animal;
• Proficiency in micro-injections and zebrafish husbandry are required;
• A successful candidate should be a highly motivated, organized, reliable team player who can also work independently;
• Excellent communication in English is required, both orally and in writing.

Merits:

• Prior knowledge and experience in fluorescence microscopy, data management, and image-based analyses are a bonus.

Apply NowDeadline 15 August