Robert

Moulder

With recent improvements in chromatographic and mass spectrometry technology it has been increasingly possible to provide detailed proteomic information of complex samples in a time efficient manner. Such characterizations of biological systems can provide important insight into cell biology and disease pathologies. Following this theme, my research pursuits are divided into two related categories, proteomic biomarker identification and proteomics characterization of cells pertinent to the immune system. Using samples collected in the Finnish Diabetes Prediction and Prevention (DIPP) study I have used mass spectrometry based quantitative proteomics to identify early changes and risk related differences in the temporal proteomes of children that develop type 1 diabetes in comparison with age, gender and risk matched controls. Our publication of this research presented the first detailed temporal proteome of children at risk from T1D. Following on from this work further validations in independent cohorts are in progress, in addition to other T1D research and related studies. Similarly, using longitudinal samples we have studied the differences in the serum protein profiles of subjects with asymptomatic cardiovascular atherosclerosis. The key genetic component for T1D is found amongst variants of the human leucocyte antigen (HLA) gene, the functions of which include activatation of CD4+ T cells. As inappropriate CD4+ T helper cell activation and polarization have been linked with several inflammatory and autoimmune diseases, an understanding of the molecular mechanisms of these processes is important in identifying the pathologies of related disease states. We have used quantitative proteomics to study the early changes in the differentiation process, including published proteomics works on Th17, Th2 and Th1 cells, including complementary genomics. Ongoing work concern the use of targeted and non-targeted proteomics to analyse these and other Th cell subsets, detailing protein interactions and temporal profiles.