Uppsala University is a comprehensive research-intensive university with a strong international standing. Our mission is to pursue top-quality research and education and to interact constructively with society. Our most important assets are all the individuals whose curiosity and dedication make Uppsala University one of Sweden’s most exciting workplaces. Uppsala University has 42,000 students, 7,000 employees and a turnover of SEK 6.7 billion.
The Department of Immunology, Genetics and Pathology at Uppsala University (www.igp.uu.se) has a broad research profile with strong research groups focused on cancer, autoimmune and genetic diseases. A fundamental idea at the department is to stimulate translational research and thereby closer interactions between medical research and health care. Research is presently conducted in the following areas: medical and clinical genetics, clinical immunology, pathology, neuro-oncology, vascular biology, radiation science and molecular tools. Department activities are also integrated with the units for Oncology, Clinical Genetics, Clinical Immunology, Clinical Pathology, and Hospital Physics at Akademiska sjukhuset, Uppsala. The department has teaching assignments in several education programmes, including Master Programmes, at the Faculty of Medicine, and in a number of educations at the Disciplinary Domain of Science and Technology. The department has a yearly turnover of around SEK 400 million, out of which more than half is made up of external funding. The staff amounts to approximately 340 employees, out of which 100 are PhD-students, and there are in total more than 600 affiliated people.
The student will be placed in the Lymphangiogenesis Lab research group lead by Kaska Koltowska (koltowskalab.com). Our research group studies lymphatic vessel formation in zebrafish, as a main model system. Lymphatic vessels are predominantly derived from a defined venous, vascular network, posing an intruding question of how cells know to form one vasculature from another. The overarching goal of my lab is to broaden our understanding of how lymphatic vessels form and establish function; and apply this knowledge to the development of new therapeutics.
Project description: Lymphangiogenesis includes the sprouting, migration and elaboration of new lymphatics from pre-existing vessels in both development and disease. The apical signalling pathway in lymphangiogenesis is the VEGFC/VEGFR3 pathway, yet how signalling controls cellular transcriptional output remains unknown. We used a forward genetic screen in zebrafish to identify the transcription factor mafba as essential for lymphatic vessel development. We found that mafba is required cell autonomously for the migration of lymphatic precursors after their initial sprouting from the posterior cardinal vein.
The main aim of this project is to characterise the migratory powerhouse downstream of mafba essential for lymphangiogenesis. In this project, the student will generate CRISPR mutants and characterise their role in lymphatic development.
Main techniques and analysis required in this project: RNA sequencing, CRISPR-Cas9 gRNAs technology, generation and maintenance of zebrafish lines, confocal fluorescence microscopy, immunohistochemistry, in situ hybridisation, objective quantification of imaging data, quality control, large data sets and statistical analysis, manuscripts preparation.
The student will receive a thorough education in molecular biology, zebrafish husbandry, fluorescence microscopy and handling of large datasets.
The successful candidate will devote most of the time towards his/her research level education. Other service activities within the department, e.g. education and administrative work can be included within the framework of the employment (maximum 20%). The position will be extended with the time devoted to teaching to allow four years of full time graduate studies.
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 is basic knowledge of, and skills in molecular biology. A successful candidate should be a highly motivated, organized, reliable team player that can also work independently. Prior knowledge and experience in fluorescence microscopy, bioinformatics, programming, zebrafish husbandry and/or image-based analyses are a bonus.
The application should include:
1) a cover letter describing yourself, your research interests and your experience relevant to this position.
2) a CV/resume; a verified list of course grades; and contact details for at least two reference persons.
3) 2 page synopsis of the most recent discoveries in zebrafish lymphatic development (including reference list).
4) If available, a Master thesis (completed or in draft form) and letters of recommendation can also be included.