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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.

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

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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