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Single-cell and live-imaging approaches to study Intra-tumor Heterogeneity and Population Dynamics in Colorectal cancer organoids

Project description

Intra-tumour cellular heterogeneity in metastatic colorectal cancer

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide, leading to around one million deaths each year. Recent findings suggest that intra-tumour cellular heterogeneity plays a significant role in therapy resistance, but the effects of different subpopulations on tumour biology remain poorly understood. Supported by the Marie Skłodowska-Curie Actions programme, the POPYNA project will explore intra-tumour phenotypic heterogeneity and subpopulation interactions in metastatic CRC using advanced techniques. The project will employ single-cell RNA sequencing to identify and characterise distinct subpopulations in human-derived organoids, monitor their plasticity through fluorescent reporter lines and live imaging, and assess their impact on tumour growth while uncovering underlying molecular pathways.

Objective

Colorectal cancer (CRC) is one of the most diagnosed cancer worldwide. Though several treatment strategies are available today, around a million people die of this disease each year worldwide. Thus, there is still a pivotal need for new and more effective treatments. Intra-tumor cellular heterogeneity has emerged lately as an intrinsic feature of malignancies and as one of the factors responsible for therapy resistance or tolerance. However, the role that phenotypically distinct subpopulations have on tumor biology is far from being understood. This multi-disciplinary proposal is based on the use of cutting-edge techniques to unravel the basic features of intra-tumor phenotypic heterogeneity and subpopulations interactions. The goals are to (1) identify and characterize phenotypically distinct subpopulations on a set of metastatic CRC human-derived organoids by single-cell RNA sequencing; (2) monitor their plasticity (transitions) by generation of fluorescent reporter lines and live-imaging lineage tracing; (3) study the impact of each subpopulation on tumor growth, and identify underlying molecular pathways by live-imaging. Ambitiously, this project aims at witnessing phenotypic transitions in living cells, a challenging task that has not been fully accomplished yet, with relevant therapeutic consequences.
It is expected that this project will provide the scientific community with a deeper understanding on subpopulations dynamics in colorectal cancer, that could ultimately result in the discovery of novel treatment strategies, such as targeting a specific subpopulation or interfering with molecular determinants of transitions. Moreover, it will foster the independent career of the applicant as a researcher by expanding her skills and international network. This project tackles a relevant problem of modern cancer biology by employing innovative techniques, complemented with state-of-the-art facilities and high quality training and mentoring.

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

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

UNIVERSITA DEGLI STUDI DI TORINO
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.

€ 172 750,08
Address
VIA GIUSEPPE VERDI 8
10124 TORINO
Italy

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Region
Nord-Ovest Piemonte Torino
Activity type
Higher or Secondary Education Establishments
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Total cost

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