Objective
Sarcomas are an extremely heterogeneous group of mesenchymal cancers, many of which remain lethal despite decades of clinical trials. A unifying characteristic in pediatric sarcomas is their low mutational burden. Instead, they frequently harbor an entity-specific chromosomal rearrangement giving rise to an oncofusion protein that acts as the disease driver. This genetic simplicity underlying a complex group of tumors implies a synergy between oncofusions and the cellular context in which they occur. However, the cell-of-origin for the vast majority of sarcomas is unknown. We have developed a flexible method for somatic engineering of the mouse muscle to model more than 10 genetically distinct pediatric sarcoma subtypes. Here we will take advantage of this unique tool to understand key questions so far unanswered due to the lack of suitable sarcoma models and flexible genetic approaches:
1.What is the identity of the cell(s) of origin and why are they permissive to transformation?
2.Are gene fusions required for tumor maintenance? And if they are, to what extent is transformation reversible? Do tumor cells retain memory of their previous normal states? Or there is a point of no return when they forget what they used to be?
By combining our models with transgenic mouse lines that allow in vivo cell barcoding, we will trace, isolate and characterize different population of cells in normal muscle and in primary tumors to identify and study sarcoma cells-of-origin. To understand the role of gene fusions in tumor maintenance we will apply the degradation system (dTAG) for in vivo acute degradation of oncofusion proteins. Temporal and spatial analysis will allow to dissect complex biological responses to oncogene withdrawal. These approaches will combine cutting-edge technologies to provide fundamental knowledge on the mechanisms underlying tumorigenesis, their intertwining with existing cellular states and the potential of oncofusion withdrawal for sarcoma treatment.
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 biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
You need to log in or register to use this function
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.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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
See all projects funded under this funding scheme
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-2024-COG
See all projects funded under this callHost institution
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.
69120 Heidelberg
Germany
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.