PhD Position in Type 1 Diabetes Research KU Leuven, Clinical and Experimental Endocrinology

Prof Chantal Mathieu’s research team focuses on the pathogenesis of type 1 diabetes (T1D). Research areas of interest are in particular focusing on the special nature of the beta-cell, the possible role in its own destruction and more recently the specific role of inflammation-mediated post-translational modifications in the generation of beta-cell neo-autoantigens. Also her lab is well equipped for performing preclinical studies making use of animal models in T1D and especially demonstrating the value of the vitamin D hormone as a natural immune modulator. Recently her team brought antigen-specific therapies into a new dimension by oral delivery of antigens through genetically modified Lactococcus lactus bacteria. The diabetes research group is part of the Laboratory of Clinical and Experimental Endocrionology, located at Campus Gasthuisberg, KU Leuven. Prof. Mathieu is the coordinator of a large-scale EU consortium INNODIA on translational approaches to disease modifying therapy of type 1 diabetes: an innovative approach towards understanding and arresting type 1 diabetes (www.innodia.eu). The available PhD position will fit in the frame of this EU consortium.

Applications are invited for a PhD position at the Laboratory of Experimental Medicine and Endocrinology at the KU Leuven, Leuven, Belgium for a project on ‘Post-translationally modified beta-cell proteins: a driving force behind type 1 diabetes?’.

 

The laboratory of Clinical and Experimental Endocrinology, headed by Prof. dr. Chantal Mathieu, has a position available for a highly motivated PhD student to study beta-cell autoimmunity with a strong focus on the interaction between immune system and insulin-secreting beta cells.

 

The position fits within the research interests of the lab, where studies are conducted on the pathogenesis, prevention and intervention of autoimmune type 1 diabetes in pre-clinical models and immunological assays (dr. Conny Gysemans), research of beta-cell dysfunction and death pathways and their signaling towards the immune system (dr. Lut Overbergh), as well as translational research in patients (prof. dr. Chantal Mathieu). Type 1 diabetes is an autoimmune disease characterized by progressive destruction of the insulin-secreting beta cells. It is a complex disease that results from the loss of tolerance to beta-cell autoantigens. This loss of tolerance can be caused by modifications of beta-cell autoantigens, generating 'neo-autoantigens’, and inducing autoreactive T-cell responses. The Mathieu lab found that post-translational modifications, i.e. citrullination, of ER chaperones and their subsequent translocation to the plasma membrane of a dying beta cell impacts on type 1 diabetes pathogenesis progression in mice (Rondas D et al. Diabetes, 2015, 64(2):573-86). These findings were translated to the human pathology (Babon et al. Nature Med, 2016;22(12):1482-1487; and Buitinga et al., work submitted).

 

Post-translational modifications of beta-cell autoantigens provide a novel hypothesis to understand how autoreactive T cells can escape immune tolerance and cause destruction of beta cells. Additionally, aberrant proteins produced by stressed beta cells can cause their own destruction. This path of research will be taken to the next level in both preclinical in vivo studies and in human patient material. Experiments will involve cell culture, multi-color flowcytometry, confocal immunofluorescent microscopy, transmission electronmicroscopy, in vivo animal models, mass spectrometry, and standard biochemical/molecular approaches. 

 

- Candidates must have a master in the field of biomedical sciences or equivalent.

 

- The candidate has excellent communication skills in written and spoken English.

 

- He/she is highly motivated to work in a multidisciplinary research team, as well as independently, has an open communication style and has a problem-solving attitude.

• As this PhD project is part of a large-scale international consortium INNODIA (www.innodia.eu), the candidate will be embedded in an international research team, where basic researchers and clinicians work closely together. 
• The candidate will have access to state-of-the-art technologies and a rich training environment.
• We offer a fully funded 4-year PhD position. 

For more information please contact Mrs. Lut Overbergh, tel.: +32 16 37 74 66, mail: lutgart.overbergh@kuleuven.be. For applying, please send your CV, a motivation letter and contact information of 2 referees to Dr. Lut Overbergh (lutgart.overbergh@kuleuven.be) and Prof. Chantal Mathieu (chantal.mathieu@kuleuven.be)