Project description
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.
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 (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
- medical and health sciences clinical medicine oncology
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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-2018
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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.
M13 9PL Manchester
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.