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Regulation of (ADP-ribosyl)ation signalling in the DNA damage response: elucidating the function of a novel PARP1/ARTD1 interactor

Objective

(ADP-ribosyl)ation is a dynamic post-translational modification synthesised by PARPs/ARTDs and regulates a diverse array of cellular processes, including the DNA damage response (DDR). The last decade has significantly improved our understanding of the key enzymes involved in (ADP-ribosyl)ation and the cellular pathways they function within. However, our understanding of how these enzymes are regulated is lacking and demands further investigation. In this proposal I seek to redress this.
I have provided promising preliminary data identifying a novel uncharacterised interactor of PARP1 involved in the DDR. I expect that this novel protein will have a fundamental role in PARP1 biology in cells given that the two have co-evolved and form a protein complex in cells.
I will implement newly available cutting-edge technologies, such as CRISPR-Cas9 and quantitative cell biology approaches, into an interdisciplinary strategy involving genetics, cell biology, structural biology and biochemistry. This strategy will allow me to address the following research objectives: (1) elucidate the function of this protein complex in genome maintenance (2) determine the atomic structure of the complex (3) define the physiological function of the protein complex using genetic mouse models.
This timely and holistic approach will allow me to answer crucial outstanding questions related to the regulation of (ADP-ribosyl)ation signalling for the first time. Consequently, this will be the first mechanistic study of its function and therefore my research objectives are likely to yield original insights into novel aspects of (ADP-ribosyl)ation signalling.
The objectives described in this proposal will enhance my potential to become an independent investigator by promoting the diversification of my technical competences through training at a world-leading institute and host laboratory. Therefore, the proposal is well aligned with the over-arching aims of the Work Programme.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2015

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

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.

€ 183 454,80
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 183 454,80
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