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Regulation of early colorectal cancer tumorigenesis by nutrient signalling of intestinal stem cells and their tissue environment

Objective

Colorectal cancer (CRC) is the second most common cancer and nutrition influences its prevalence. CRC originates from intestinal stem cells (ISCs) and is initiated by specific genetic alterations, which influence cell growth, proliferation and fate. How nutrient signalling within the mutated ISCs and the surrounding tissue environment influences the early steps of CRC tumorigenesis and whether genetically distinct tumour types react differently to nutrition remains poorly understood. The host laboratory has recently discovered a mechanism that couples nutrient-dependent control of ISC size to cell fate regulation. As distinct tumorigenic genotypes display different fate profiles, I hypothesise that nutrient-dependent control of ISC size differentially modulates phenotypes of CRC-associated gene variants. To test this, I will utilise the Drosophila midgut model as well as the fully defined Drosophila diet to systematically uncover the nutrient vulnerabilities of several ISC-derived tumorigenic genotypes. As my preliminary data implicates the role of nutrient signalling in the tissue environment, I will develop a new dual gene expression tool, enabling simultaneous genetically control of the tumour and the neighbouring tissue. I will combine transcriptomics, metabolomics and organ-wide imaging with quantitative image analysis to mechanistically address how changes in nutrient signalling and metabolism of oncogenic and surrounding wild-type cells influence tumour initiation. To test the conservation of the main findings in Drosophila, I will utilise the CRC models of mouse intestinal organoids. Collectively, this project will address how nutrient regulation of ISCs and their tissue environment will affect the initial events of CRC tumorigenesis.

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Keywords

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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.

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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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) HORIZON-MSCA-2022-PF-01

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Coordinator

HELSINGIN YLIOPISTO
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.

€ 215 534,40
Address
FABIANINKATU 33
00014 HELSINGIN YLIOPISTO
Finland

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Activity type
Higher or Secondary Education Establishments
Links
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.

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