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

Informacje na temat projektu

TEATIME

Identyfikator umowy o grant: 101110041

DOI 10.3030/101110041

Data podpisania przez KE 4 Maja 2023

Data rozpoczęcia 1 Stycznia 2024

Data zakończenia 31 Grudnia 2025

Finansowanie w ramach

• Marie Skłodowska-Curie Actions (MSCA)

Koszt całkowity Brak danych

Wkład UE € 215 534,40

Koordynowany przez

HELSINGIN YLIOPISTO
Finland

Cel

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.

Dziedzina nauki (EuroSciVoc)

Klasyfikacja projektów w serwisie CORDIS opiera się na wielojęzycznej taksonomii EuroSciVoc, obejmującej wszystkie dziedziny nauki, w oparciu o półautomatyczny proces bazujący na technikach przetwarzania języka naturalnego.

• medycyna i nauki o zdrowiu › medycyna kliniczna › onkologia

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Słowa kluczowe

• stem cell
• intestinal cancer
• Drosophila
• nutrient sensing
• metabolism

Program(-y)

• HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme

Temat(-y)

• HORIZON-MSCA-2022-PF-01-01 - MSCA Postdoctoral Fellowships 2022

Zaproszenie do składania wniosków

HORIZON-MSCA-2022-PF-01

System finansowania

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

Koordynator

HELSINGIN YLIOPISTO

• Wkład UE netto: € 215 534,40
• Adres: FABIANINKATU 33 ; 00014 HELSINGIN YLIOPISTO ; Finlandia
• Rodzaj działalności: Higher or Secondary Education Establishments
• Koszt całkowity: Brak danych