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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.

Field of science

  • /medical and health sciences/clinical medicine/cancer/colorectal cancer
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /agricultural sciences/agriculture, forestry, and fisheries/agriculture/horticulture/fruit growing
  • /medical and health sciences/clinical medicine/ophthalmology
  • /natural sciences/biological sciences/developmental biology
  • /natural sciences/biological sciences/zoology/mammalogy

Call for proposal

H2020-MSCA-IF-2014
See other projects for this call

Funding Scheme

MSCA-IF-EF-ST - Standard EF

Coordinator

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 195 454,80