Innovating Works

SpatialOrganoids

Financiado
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... 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. ver más
31/12/2022
UZH
191K€
Duración del proyecto: 32 meses Fecha Inicio: 2020-04-15
Fecha Fin: 2022-12-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2022-12-31
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
Presupuesto El presupuesto total del proyecto asciende a 191K€
Líder del proyecto
UNIVERSITAT ZURICH No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5