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Regulation of early colorectal cancer tumorigenesis by nutrient signalling of in...
Regulation of early colorectal cancer tumorigenesis by nutrient signalling of intestinal stem cells and their tissue environment 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, prol... 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. ver más
31/12/2025
HELSINGIN YLIOPIST...
216K€
Perfil tecnológico estimado
Duración del proyecto: 31 meses Fecha Inicio: 2023-05-04
Fecha Fin: 2025-12-31

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-05-04
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2022-PF-01-01: MSCA Postdoctoral Fellowships 2022
Cerrada hace 2 años
Presupuesto El presupuesto total del proyecto asciende a 216K€
Líder del proyecto
HELSINGIN YLIOPISTO No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5