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. . .the grantees are internationally recognized for their work in regulatory T cells for Fiona Powrie and fundamental and clinical proteomics for Matthias Mann. For the third time, EMBO Molecular Medicine is delighted to publish commentaries from this year's winners, ‘Gut reactions: Immune pathways in the intestine in health and disease’ (Powrie, 2012) and ‘Proteomics for biomedicine: A half-completed journey’ (Mann, 2012). Fiona Powrie trained as a PhD student in Immunology in Oxford, where she worked in Don Masons' lab. Following postdoctoral research in the USA, she returned to Oxford and has worked there ever since. Her seminal work identified functionally distinct subsets of CD4+ T cells that suppress immune responses and whose absence causes inflammatory disease. Powrie further identified the functional role of regulatory T (Treg) cells in maintaining intestinal homeostasis, tracing their lineage and identifying their mode of action. The gastrointestinal tract is home to a multitude of bacteria, and it is clear now that the intestinal microbiota plays a major role in modulating the host immune response and in the defence against pathogens. However, aberrations in this commensal relationship cause potentially fatal inflammatory responses. Well-known examples of such a detrimental effect are the inflammatory bowel diseases (IBD) encompassing Crohn's disease and ulcerative colitis. Powrie's work has shown how important it is to maintain a fine balance in the gut of beneficial bacteria, while avoiding infections. In that respect, both adaptive and innate immune mechanisms contribute to intestinal inflammation and Powrie's lab identified the pro-inflammatory cytokine IL-23 as a key modulator/effector of the development of pathogenesis of chronic intestinal inflammation. Effector T cells were shown to drive inflammation via a Th17 immune response while regulatory T cells suppress it. A defect in Treg number or function can result in IL-23 driven chronic intestinal inflammation, suggesting that Tregs could be used as therapeutic agent against chronic inflammatory disease. With the Louis Jeantet Prize, Fiona Powrie will undoubtedly continue to unravel the immune mechanisms that help our gut to stay healthy. Specifically, she will aim at better understanding how particular bacteria and their metabolites differentially affect effector and regulatory T cell responses. How changes in the microbiota of the gut activate the immune system and the impact of this on disease progression remains largely unknown. Matthias Mann studied mathematics and physics in Göttingen and obtained his PhD from Yale University where he worked with John Fenn on electrospray mass spectrometry (for which John Fenn was awarded the Nobel Prize in Chemistry in 2002). This pioneering work paved the way to modern proteomics, the global analysis of proteins. Over the last 25 years, the field of proteomics has evolved so much that it is now possible to detect and characterize with high sensitivity thousands of proteins, mapping structure and function globally onto any biological system. Recent advances, both in terms of instrumentation, computational analysis and sample preparation, to which the Mann lab has critically contributed, allow for accurate quantification of proteins across varying conditions. Proteomic applications in medicine range from the characterization of differential proteomes between normal and disease state to tissue specific proteomes, including formalin-fixed samples, or marker of expression in body fluids such as urine or plasma. Modern mass spectrometry techniques are capable of identifying different post-translational modifications or diverse protein interactions. With these progresses, proteomics can now be successfully applied to all areas of research and medicine and be used to identify specific markers of a disease, progression stage and potential drug resistance. One famous discovery of the Mann's lab is SILAC (stable isotope labelling by amino acids in cell culture), the most accurate proteome quantification method, enabling detection and characterization of proteins via their interactions, modifications and cellular localizations. Recently Matthias Mann's group reported the proteome of a single cancer cell type, thereby providing proof of principle for clinical proteomics which will allow very precisely quantifying and cataloguing thousands of proteins that may be used as biomarkers or protein signatures to guide clinicians in diagnosis, prognosis and better adapted treatment of human diseases. This is the ambitious project that the lab will focus on in the coming years aided by the Jeantet prize. On behalf of EMBO, we wish to congratulate the 2012 Louis Jeantet Prize winners, and look forward to an exciting decade in Molecular Medicine research. The authors declare that they have no conflict of interest. Céline Carret Céline Carret is an editor of EMBO Molecular Medicine at EMBO. European Molecular Biology Organization, Heidelberg, Germany E-mail: [email protected] Bernard C. Rossier Bernard C. Rossier is Emeritus Professor, University of Lausanne, Secretary of the Scientific Committee and Vice President of the Louis Jeantet Foundation E-mail: [email protected]