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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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 Outcomes and results

 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.

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

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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