Objective
In the human genome, many G-rich sequences have the potential to form 4-stranded non-canonical secondary structures known as G-quadruplexes (G4s). G4 structures have been visualized in nuclei by immunofluorescence and mapped genome-wide to regulatory chromatin regions linked to elevated transcription using G4 chromatin immunoprecipitation and high-throughput sequencing (G4 ChIP-seq). G4s are implicated in gene regulation, DNA replication and genome instability, yet little is known about their protein interaction partners or role in regulating genome activity.
We therefore propose to develop G4 Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins (G4 RIME) methodologies to elucidate the G4 interactome within a native chromatin context. ChIP-seq of protein candidates coupled with G4 ChIP-seq will verify binding at endogenous G4 structures. Using established biophysical and biochemical techniques, we will investigate binding modes, recruitment and effects on G4 dynamics. Consecutive chromatin immunoprecipitation steps using antibodies targeting characteristic chromatin marks as well as G4 ChIP-seq supported by bioinformatics analysis of genomic databases will identify proteins involved in transcriptional regulation. We will then test the consequence of stabilising G4s with small molecule ligands on the G4 interactome and how this is modulated during genomic stress. Cells genetically deficient in G4-interacting proteins will enable detailed exploration of G4 formation and transcriptional effects.
This highly interdisciplinary project will provide a wide range of excellent training opportunities exploiting the Balasubramanian group’s unique position with laboratories at the Cancer Research UK Cambridge Institute (CRUK CI) and the Department of Chemistry. Overall, the studies will generate novel functional insights in the G4 biology that may ultimately lead to the identification of mechanisms and pathways for new anti-cancer agents.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
- natural sciences chemical sciences analytical chemistry mass spectrometry
- natural sciences biological sciences genetics genomes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2016
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
CB2 1TN CAMBRIDGE
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.