The beta-cell in the pathogenesis of type 1 diabetes: focus on translational and post-translational events.

Type 1 diabetes (T1D) is a disease where the bodys own immune system destroys the pancreatic beta-cells. Understanding the origin and development of T1D will pave the way to prevention and cure. In the present project, I will further unravel the abnormalities present in beta-cells already before the onset of the disease and the events which are taking place in the beta-cell under immune attack. I will concentrate on abnormalities at the protein and post-translational level. In a first part I wish to gain more insight in how T1D is initiated. As a second aim I will investigate the pathways involved in immune-mediated beta-cell dysfunction and death. In a third aim I will look into the secretory vesicles of the beta-cell, identifying the proteins and peptides present in this organelle, in an attempt to find new auto-antigens. For all these studies I will make use of sophisticated proteomics techniques (2D-DIGE and MS/MS), combined with systems biology tools and newly developed software programs to analyze post-translational modifications in the proteins of interest. The studies proposed will provide a more complete view of our current understanding of abnormalities that are taking place at the level of the beta-cell.

Keywords:Secretory, Granules, Systems biology, Peptidomics, Type 1 diabetes, Post translational modifications, Proteomics

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences