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Development of a model system to study the role of chromatin factors during transgenerational epigenetic inheritance (TEI) in C. elegans

Objective

Non DNA-sequence based inheritance has been observed in many organisms from microbes to man and likely impacts public health. The mechanisms of non DNA-sequence based inheritance remain largely unknown. However, some examples of non DNA-sequence based inheritance in mammals, plants and invertebrates are linked to the control of selfish, transposable elements in the genome. Here we propose to discover the mechanistic basis of multi-generational non DNA-sequence based inheritance, also referred to as transgenerational epigenetic inheritance (TEI), using the laboratory animal model Caenorhabditis elegans. Specifically, our goal is to identify chromatin and non-coding RNA “epigenetic” marks that transfer information from generation to generation in C. elegans. C. elegans is a great model for this work as it has a generation time of only three days, has a powerful genetics toolkit and its chromatin and RNA pathways are largely conserved in humans. Towards this goal we have established a novel assay we named piRNA-related insertional chromatin immunoprecipitation (piChIP). Using this piChIP system, our specific aims are:
Aim-1: Identification of novel non-coding RNAs in the germline nuclear RNAi pathway
- Method: RNA-seq
Aim-2: Identification of novel proteins and histone PTMs in the germline nuclear RNAi pathway
- Method: SILAC proteomics and Mass Spectrometry

Call for proposal

H2020-MSCA-IF-2016
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Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 183 454,80