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Spatial-temporal regulation of APC/C, its role on G1 arrest and impact on terminal differentiation

Objective

Coupling the cell-autonomous process of the cell cycle with spatiotemporal clues that promote the differentiation process is a major challenge in developmental biology. The retina aberrant in pattern (rap) gene was initially identified as a retina differentiation and patterning gene in Drosophila. It was later discovered to encode Fizzy-related (Fzr), a coactivator of the cell cycle regulator, Anaphase Promoting Complex/Cyclosome (APC/C). This was a critical initial step towards establishing a link between differentiation and cell cycle regulation. This project aims to understand the coordination between mechanisms of proliferation and differentiation, with a particular focus on the APC/C complex. The requirement of individual APC/C components to sustain the developmentally controlled G1 arrest and its subsequent effects on terminal differentiation will be addressed. The transcriptional and posttranslational regulation of each APC/C component will be assayed during eye development. Next, functional APC/C interactors will be identified through two complementary screens. An in vivo gain-of-function overexpresion screen will be performed, to identify the genes that can induce cell cycle arrest in overproliferating tissues, using the newly developed FlyORF library. Additionally, a proteomic analysis of APC/C components will be performed to identify eye-specific APC/C interactors. With the information gained I will investigate how the activity and expression of the APC/C is spatial-temporally controlled by signalling cascades during eye development, and how the APC/C in turn modulates the activation and output of those signalling pathways. Overall, the insights from this project will contribute to our understanding of complex diseases such as cancer and neurodegeneration.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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.

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.

(opens in new window) H2020-MSCA-IF-2014

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Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
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.

€ 195 454,80
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN Cambridge
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
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.

€ 195 454,80
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