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The molecular regulation of T helper cell subtype plasticity (ThPLAST)
Start date: Aug 8, 2011, End date: Feb 4, 2014 PROJECT  FINISHED 

Naïve CD4+ T cell differentiate into distinct lineages to achieve successful adaptive immune responses to diverse categories of pathogens. The development of these effector cells is controlled by cytokines, transcription factor interactions and chromatin modifications. In addition, several of the differentiated subtypes can interconvert, a property known as plasticity. However, the molecular regulation of flexibility of this subset cells is still unresolved. I propose to explore the molecular machinery of the T helper (Th) effector cells’ plasticity, specifically of Th subset 2 plasticity to Th1, as understanding of this reprogramming is a key target of autoimmune- and allergen-specific immunotherapy.I plan to study the regulation of Th2-Th1 cell plasticity both experimentally and computationally. I will identify the gene expression level dynamics as well as the epigenetic events during plasticity using RNA- and ChIP-deep sequencing. These results will be processed by computational tools to define the hierarchy and dynamics of molecular regulators, and to predict key molecular players (transcription factors, microRNAs) responsible for expression of the specific cytokines. I will also monitor specific RNA and protein expression at a single cell level, and identify specific regulatory interactions, including the nucleic acid motifs involved.This research will reveal insights into the balance between lineage commitment and plasticity, which is a key question in developmental biology, and in general will impact a wide range of areas in biology from stem cell biology to cancer.
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