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Project

Single cell RNA and small non-coding RNA sequencing to identify biomarkers for pathogenesis and therapy response in type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease resulting from T-cell mediated destruction of the pancreatic beta-cells causing blood glucose dysregulation. We devised a unique method for tolerance restoration in autoimmune diabetic mice using gut delivery of bacteria genetically altered to secrete proinsulin along with the immunoregulatory cytokine IL10. To facilitate clinical translation, profound insights in the mode of action and the identification of robust (peripheral) biomarkers not only uncovering disease progresses, but also measuring responses to therapies, and predicting the prognosis of patients are needed. We propose to analyze peripheral blood and islet derived T-cells during disease progression in diabetes-prone NOD mice and from therapy responder and non-responder mice. Single cell transcriptomes and T-cell receptor repertoires of islet derived Tcells may provide insights into the regulation of T-cell identity and phenotypes, which may be very different from those in the circulation and which might be linked to the progression of T1D, its underlying heterogeneity and therapy responsiveness. Moreover, small non-coding RNAs (sncRNAs) present in the periphery and target organ will be characterized using a deep sequencing approach to evaluate the potential use of circulating sncRNAs as tissue-specific biomarkers of T1D development and therapy response. Finally, samples from T1D patients avaible through INNODIA and EUnPOD platform will be used for human validation.

Date:1 Jan 2019 →  31 Dec 2022
Keywords:Medical genomics
Disciplines:Endocrinology, Medical genomics