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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.

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

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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