Project description
Cancer cell clones and tumour biology
Cancer cells undergo genetic mutations and diversify over time, leading to the emergence of different subpopulations or clones within a tumour. This genetic diversification reinforces tumour progression and metastasis as well as the emergence of resistance to therapies. Understanding clonal evolution is crucial for developing more effective cancer treatments. Funded by the European Research Council, the SpaceClones project aims to investigate cell interactions within tumours using cell engineering and imaging techniques. The idea is to unravel molecular mechanisms governing clonal behaviours and decode spatial patterns, offering important insight into the role of cancer cell clones in tumour biology.
Objective
Clonal evolution in tumours, the process by which cancer cells expand, diversify and are selected, is a major determinant of tumour growth and response to therapy. How the co-existence of diverse cancer cell clones shape tumour development is a fundamental question that remains open, in part because of limitations on existing experimental platforms and analytical frameworks. Our expertise inferring multicellular behaviours within tissue microenvironments, together with recent advances in imaging, assay automation, and cell engineering, timely place us in an excellent position to profile and engineer clonal interactions within tumours from the tissue level down to the molecular scale, which enables targeting this important question with unprecedented throughput and spatial resolution. In SpaceClones, we aim to: (1) characterize clonal interactions in genetically engineered tumours at sub-100 nm resolution, (2) characterize clonal signatures under metabolically defined environmental conditions, and (3) examine the cell state of engineered clonal spatial patterns. To overcome a variety of challenges to understanding molecular and cellular mechanisms of clonal behaviours in tumours, I have designed a ground-breaking approach that combines highly-multiplexed imaging, in vitro and in vivo tumour models, cell engineering, super-resolution microscopy, combinatorial low-volume liquid handling, and algorithms for deconstruction of spatial patterns. Altogether, SpaceClones will exemplify how to imply causality on the emergence of clonal spatial patterns in tumours, having far-reaching implications for the study of any other multicellular system. Ultimately, a deeper understanding of clonal evolution will contribute in the design of more effective cancer therapies and tools to predict clinical outcomes.
Fields of science
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
08028 Barcelona
Spain