Objective
The tumor microenvironment (TME) is a dynamic ecosystem wherein tumor cells, immune cells and stromal cells interact and evolve. One of the primary characteristics of cancer progression is the diversification, selection and expansion of tumor sub-clones in manner that largely depends on the TME, e.g. through immune responses or metabolic crosstalk. Advances in single-cell and spatial genomics provide exciting opportunities for studying how tumors evolve in their tissue context, by lending an information-rich perspective on which cell subsets are present and how they might interact. However, fundamental questions, which require the knowledge of how single tumor cells are related sub-clonally, remain challenging to study through that perspective. Fundamentally - what characterizes the immediate cellular environment of successful subclones?
Here, we develop transcriptional phylogeography - a paradigm for studying tumor development in-situ, on a transcriptome-wide scale, and at single cell resolution. Our work will leverage studies by us and others that utilized CRISPR/Cas9 mutations coupled with single cell RNA sequencing to infer the lineage structure of thousands of single cells at a time. Adapting this system for in-situ profiling, we will generate the first of its kind phylogeography dataset of a tumor model. This data will allow us to identify tissue locations that harbor critical sub-clonal properties such as unrestrained growth, dedifferentiation, and metastatic seeding, and thereby investigate - through the lens of high throughput genomics- how the TME is associated with these properties. We will also identify and offer solutions for outstanding analytical questions in this nascent area, from lineage inference given sparse data to characterizing the metabolic aspects of tumor-TME cross talk. Together, these studies will help establish new causal links between the TME and tumor evolution and lay the foundation for transcriptional phylogeography analysis.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-COG
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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.
7610001 Rehovot
Israel
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.