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SpatialOrganoids

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Profiling the emergence of phenotypic heterogeneity in breast cancer organoids

Cell-to-cell heterogeneity in biological systems has been broadly studied in unicellular organisms and mammals. Furthermore, non-genetic, in addition to genetic heterogeneity has been recently proposed to support tumour growth and... ver más

31/12/2022

UZH

191K€

Presupuesto del proyecto: 191K€

Líder del proyecto

UNIVERSITAT ZURICH No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2022-12-31

MSCA-IF-2019: Individual Fellowships

I+D

Cerrada hace 5 años

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3 Participantes

UZH

191.15K€ | Lider

FONTESTAD CITRUS

347.71K€ | Participante

ZUMOS VALENCIANOS DEL MEDITE...

371.30K€ | Participante

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Duración del proyecto: 32 meses Fecha Inicio: 2020-04-15
Fecha Fin: 2022-12-31

Líder del proyecto

UNIVERSITAT ZURICH No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 191K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Cell-to-cell heterogeneity in biological systems has been broadly studied in unicellular organisms and mammals. Furthermore, non-genetic, in addition to genetic heterogeneity has been recently proposed to support tumour growth and to induce resistance to cancer therapy. However, the molecular events on a spatial and temporal level that lead to the emergence of tumour heterogeneity are largely unknown. To address this question, I will study breast cancer, which shows the highest cancer incidence in women and is characterised by extensive intra- and inter-patient heterogeneity in cellular and molecular phenotypes. As model system, I select 3D organoid cultures, which are gaining popularity in cancer research due to their ability to reconstruct tumour-like molecular features and to recapitulate treatment response. Here, I propose experimental and computational time-course analyses of breast cancer organoids to understand molecular and spatial determinants that underlie the emergence of heterogeneity in cancer cell phenotypes. On the experimental side, I will use imaging mass cytometry and perturbation experiments to capture and validate spatio-temporal changes in cellular phenotypes, interactions and signalling networks. Statistical modelling will quantify dynamic changes in phenotypic heterogeneity over the time-course of organoid growth. Finally, I will predict the emergence of intra-organoid heterogeneity across multiple organoid lines, which allows me to derive targeted treatment strategies. In sum, the proposed work will disentangle and perturb the spatio-temporal emergence of phenotypic intra-tumour heterogeneity, which is characteristic of breast cancer tissues.

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