Project description DEENESFRITPL Role of the recycling endosomes in tumour interaction with the stroma Endocytosis of cell surface receptors regulates signalling during differentiation, proliferation, and migration of cells. Invasive cancer cells accumulate recycling endosomes at protrusions, delivering receptors for extracellular matrix, regulating tumour cells interactions with microenvironment, and coordinating actin polymerisation through Rho family GTPases. The Rab11 GTPase family is implicated in determining the aggressiveness of high-grade serous ovarian carcinoma (HGSOC). The EU-funded EndoPos project aims to determine recycling endosomes positioning within HGSOC cells invading the extracellular matrix. A combination of innovative approaches will help to elucidate how localised endocytic trafficking controls tumour-stroma interactions and contributes to HGSOC progression. Show the project objective Hide the project objective Objective Endocytosis of cell surface receptors controls signaling during proliferation, differentiation and migration of cells, and plays a significant role in cancer progression. Invasive cancer cells accumulate recycling endosomes (including Rab11) at protrusions. This promotes the delivery of integrins, receptors for extracellular matrix, to regulate interactions between tumour cells and their surroundings, and coordinates actin polymerization through Rho family GTPases. The Rab11 family is particularly important in determining the aggressiveness of high-grade serous ovarian carcinoma (HGSOC). Despite its importance, the machinery that guides Rab11 trafficking and the functions of polarized trafficking are not clear in HGSOC. I aim to determine how recycling endosomes are positioned within HGSOC cells invading extracellular matrix, using BioID-based proteomics (a proximity labelling approach well established in the host lab) to identify the Rab11-associated machinery in HGSOC cells. I further aim to actively manipulate the dynamics of Rab11 positive endosomes in invading cells by developing a magnetogenetic approach to reposition endosomes in live cells, using a combination of my developed skills (including live imaging, protein engineering). Both cutting-edge methods will be applied in the most physiological and cancer relevant context to lend clinical relevance to our observations. Combining these innovative approaches will provide molecular detail and mechanistic insight to elucidate how localised endocytic trafficking controls tumour-stroma interactions in the metastatic niche and contributes to HGSOC lethality. This work will further provide targets for therapies aimed at suppressing metastasis and preventing relapse in HGSOC, a lethal form of ovarian cancer that has one of the worst survival rates (<40% 5-year survival). Moreover, this project will allow me to acquire technical skills and expertise essential for my development as an independent researcher. Fields of science engineering and technologyenvironmental engineeringwaste managementwaste treatment processesrecyclingnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesclinical medicineoncology Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator THE UNIVERSITY OF MANCHESTER Net EU contribution € 224 933,76 Address OXFORD ROAD M13 9PL Manchester United Kingdom See on map Region North West (England) Greater Manchester Manchester Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 224 933,76
