PhD position in Molecular Immunology (Basic Science research project)

What to expect

We are the UKE – the University Medical Centre Hamburg-Eppendorf [Universitätsklinikum Hamburg-Eppendorf]. A pulsating centre of health in the heart of Hamburg. When you are surrounded by that much energy and when progress sets the pace, no two days are the same. More than 14,100 employees with very different responsibilities are united by the same goal: ensuring health and well-being.

CD4+ TH17 cells underlie autoimmune diseases such as Multiple Sclerosis (MS) and Inflammatory Bowel disease (IBD) and have important roles in homeostasis and inflammation. How TH17 cells balance their pathogenic and regulatory functions is not understood. Upon their TCR engagement and co-stimulation, the CD4+ TH17 cells proliferate and remodel their metabolism to acquire TH17 steady state effector and/or pathogenic functions. Furthermore, during the resolution of the inflammatory response, TH17 cells finally convert into anti-inflammatory TR1 cells. How the metabolic switch to pathogenic TH17 cells is controlled is currently unkown but nevertheless, the identification of the gatekeeping mechanisms of TH17 cell pathogenicity portends immense therapeutic potential in autoimmunity.

Blimp1 (the product of PrdmI gene) is a terminal differentiation transcription factor for many cell types, including B and T lymphocytes, while its role in CD4+ TH17 cells remains controversial. To address the conundrum, we have conditionally deleted Prdm1 specifically in TH17 cells, in the context of a mouse model allowing us to follow in real time, the in vivo fate of the Blimp1-deficient TH17 cells. Our data indicate that Blimp1 controls both the pathogenic and regulatory fate of TH17 cells via a yet unidentified switch to their basic metabolic program.

This work program specifically addresses this hypothesis, aiming to shed light into the molecular principle(s) controlling the pathogenic TH17 cell metabolism and identify new therapeutic targets in autoimmunity.

• Fully funded research project
• Project supervision from a Molecular Biology and Epigenetics Scientist
• Integration into a small project related team with close supervision and mentoring
• Overall integration in a highly collaborative working environment of three working groups
• Weekly discussion and feedback rounds with supervisors
• Possibility to work on an established project with state-of-the-art experimental techniques
• Integration into structured institutional PhD program

This position is temporary for 3 years.

What we look forward to

• Completed academic studies in biology, biochemistry, human biology, bioinformatics or related subjects
• Basic knowledge in basic biological methods and cell culture
• Basic knowledge in either epigenetics, immunology or metabolism
• Basic knowledge in bioinformatic analysis of multi-omic data and/or work with laboratory mice
• High degree of intrinsic motivation and an aptitude for problem solving

What we can offer

• International and multidisciplinary environment at a leading European Institution, the University Medical Center Hamburg-Eppendorf (Germany)
• Access to several sophisticated mouse models (germ-free mice, Inflammatory-mediated Immune Disease models, immune cell reporter mice), multi-omics (single-cell sequencing; metabolomic screening; proteomics) along with direct access to human material for potential translational studies
• A Molecular Biology Scientific project in the fields of the Epigenetic and Metabolomic aspects of Immune-mediated Inflammatory diseases
• A FELASA A introductory course for animal experimentation
• A personal, step-by-step introduction and coaching to a variety of state-of-the-Art Molecular Biology, Immunology and Metabolomics methods, animal husbandry and in vivo mouse model experimentation.
• Weekly scientific exchange: lab meetings and journal clubs
• International collaboration with partners in European and American Academic Institutions (USA)
• Access to the soft skills programme of the institution: e.g., presenting skills, scientific writing