IdrSeq SIGNED
Discovery and characterization of functional disordered regions and the genes involved in their regulation through next generation sequencing
Total Cost €
0EC-Contrib. €
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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.
| # | ||||
|---|---|---|---|---|
| 1 | UNITED KINGDOM RESEARCH AND INNOVATION | UK (SWINDON) | coordinator | 1˙998˙126.00 |
| 2 | MEDICAL RESEARCH COUNCIL | UK (SWINDON) | coordinator | 0.00 |
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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 |
|---|---|---|---|
| 2018 |
Charles NJ Ravarani, Tamara Y Erkina, Greet De Baets, Daniel C Dudman, Alexandre M Erkine, M Madan Babu Highâ€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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