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

Projektinformationen

IdrSeq

ID Finanzhilfevereinbarung: 682414

DOI 10.3030/682414

Das Projekt endete am 30 Juni 2020

EK-Unterschriftsdatum 5 April 2016

Startdatum 1 Mai 2016

Enddatum 30 April 2021

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten € 1 998 126,00

EU-Beitrag € 1 998 126,00

Koordiniert durch

UNITED KINGDOM RESEARCH AND INNOVATION
United Kingdom

Ziel

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.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › biochemistry › biomolecules › proteins › proteomics
• natural sciences › biological sciences › synthetic biology
• natural sciences › biological sciences › cell biology
• natural sciences › biological sciences › molecular biology › structural biology
• natural sciences › biological sciences › genetics › genomes › eukaryotic genomes

Schlüsselbegriffe

• Intrinsically disordered proteins

Programm/Programme

• H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme

Thema/Themen

• ERC-CoG-2015 - ERC Consolidator Grant

Aufforderung zur Vorschlagseinreichung

ERC-2015-CoG

Finanzierungsplan

ERC-COG - Consolidator Grant

Gastgebende Einrichtung

UNITED KINGDOM RESEARCH AND INNOVATION

• Netto-EU-Beitrag: € 1 998 126,00
• Adresse: POLARIS HOUSE NORTH STAR AVENUE ; SN2 1FL Swindon ; Vereinigtes Königreich
• Region: South West (England) › Gloucestershire, Wiltshire and Bristol/Bath area › Swindon
• Aktivitätstyp: Research Organisations
• Gesamtkosten: € 1 998 126,00

Begünstigte (1)

UNITED KINGDOM RESEARCH AND INNOVATION

Vereinigtes Königreich

• Netto-EU-Beitrag: € 1 998 126,00
• Adresse: POLARIS HOUSE NORTH STAR AVENUE ; SN2 1FL Swindon
• Region: South West (England) › Gloucestershire, Wiltshire and Bristol/Bath area › Swindon
• Aktivitätstyp: Research Organisations
• Gesamtkosten: € 1 998 126,00