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IdrSeq SIGNED

Discovery and characterization of functional disordered regions and the genes involved in their regulation through next generation sequencing

Total Cost €

0

EC-Contrib. €

0

Partnership

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 IdrSeq project word cloud

Explore the words cloud of the IdrSeq project. It provides you a very rough idea of what is the project "IdrSeq" about.

cancer    assemblies    regulate    molecular    modular    selectable    contrast    therapeutic    neurodegeneration    sequencing    direct    influence    readily    phenotype    discovery    experiments    poorly    cell    eukaryotic    experiment    gene    platform    tertiary    form    encodes    cellular    vision    yeast    enriched    discover    idrseq    health    fraction    variants    diseases    relationship    simultaneously    libraries    extended    functional    coupling    exploits    genome    40    protein    functions    enormous    structural    principles    revealing    structure    idr    computation    vast    intrinsically    implications    genes    critical    genotype    assay    gt    half    stability    broad    function    linked    integrative    holds    human    synthetic    life    mediated    activate    signaling    context    disordered    elucidating    model    throughput    transcription    organisms    idrs    scalable    idps    structured    sequence    biology    code    millions    regions    sequences    generation    segments    genetics    assembly    proteins   

Project "IdrSeq" data sheet

The following table provides information about the project.

Coordinator
UNITED KINGDOM RESEARCH AND INNOVATION 

There are not information about this coordinator. Please contact Fabio for more information, thanks.

 Coordinator Country United Kingdom [UK]
 Project website https://www.mrc-lmb.cam.ac.uk/genomes/madanm/IDR-Screen/
 Total cost 1˙998˙126 €
 EC max contribution 1˙998˙126 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-05-01   to  2021-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNITED KINGDOM RESEARCH AND INNOVATION UK (SWINDON) coordinator 1˙998˙126.00
2    MEDICAL RESEARCH COUNCIL UK (SWINDON) coordinator 0.00

Map

 Project objective

A large fraction of any eukaryotic genome (>40%) encodes protein segments that do not adopt a defined tertiary structure. These proteins or regions are called intrinsically disordered proteins/regions (IDPs/IDRs). IDRs are enriched in critical functions such as transcription and signaling, and have been linked with numerous diseases including neurodegeneration and cancer. In contrast to structured regions, the molecular principles behind the sequence-function relationship of IDRs remain poorly understood.

We propose to identify functional IDRs and discover genes that regulate their function using yeast as a cellular model. We will develop and apply a targeted, high-throughput approach called IdrSeq. This technology exploits next generation sequencing to simultaneously assay vast libraries of sequences (~millions) that code for IDRs by coupling IDR sequence (genotype) to a selectable function (phenotype) and identifying functional variants through a selection experiment.

Specifically, using IdrSeq, we aim to identify and characterize IDRs in a cellular context that can (Aim 1) activate transcription, and discover genes that regulate IDR mediated transcription (Aim 2) influence protein stability, and discover genes that regulate IDR mediated half-life (Aim 3) form higher-order assemblies and discover genes that regulate assembly formation

The unique feature of this proposal is its integrative vision of synthetic & systems biology, structural biology, cell biology, genetics, experiments and computation to establish a discovery platform to study IDRs in a cellular context. Since IdrSeq is modular and scalable, it can be readily extended to investigate a broad range of IDR functions, and adapted to other organisms. Elucidating the principles of sequence-function-gene relationship of IDRs holds enormous potential for synthetic biology. The discovery of genes that regulate IDR function has direct implications for human health by revealing novel therapeutic targets.

 Publications

year authors and title journal last update
List of publications.
2018 Charles NJ Ravarani, Tamara Y Erkina, Greet De Baets, Daniel C Dudman, Alexandre M Erkine, M Madan Babu
High‐throughput discovery of functional disordered regions: investigation of transactivation domains
published pages: e8190, ISSN: 1744-4292, DOI: 10.15252/msb.20188190
Molecular Systems Biology 14/5 2019-05-27

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