Project description
Rewriting the rules for protein control
Gene-editing tools can change DNA and RNA with speed and scale. While these tools link genes to specific traits, similar methods to control proteins currently do not exist. This limits the ability to link protein changes to cell behaviour. The ERC-funded ProteinPerturbomics project aims to build a programmable system that can control many proteins at once. The team uses gene editing and induced protein proximity to tag proteins or cause their breakdown inside cells. The project follows three steps. First, it will target proteins across the human proteome. Second, it will study how drug targets interact with protein-degrading factors. Third, it will explore ways to reprogram cancer cells by changing how key proteins act. The overall goal is to create new tools for biology and support the search for potential new cancer treatments.
Objective
Programmable perturbation technologies such as CRISPR-Cas have transformed how we study biological systems by offering efficient and scalable methods to manipulate DNA and RNA, thereby linking genotype to phenotype. However, corresponding technologies for rationally manipulating all proteins have lagged behind, restricting our ability to connect proteotypes to phenotypes. Developing a programmable protein perturbation technology would be a breakthrough in the biomedical sciences, as it would facilitate the interrogation of biology and creation of medicines in fundamentally new ways. The overarching goal of this proposal is to develop and apply such a high-throughput programmable protein perturbation platform by combining tools and concepts at the intersection of gene editing, proximity-induced pharmacology, and pooled screening. Our preliminary work has already established a foundation for this, including successful demonstration of high-throughput prime editing–mediated epitope tagging and targeted protein degradation (TPD) as well as induced proximity between any two proteins of interest. In this proposal, we will build upon these advances by: 1) establishing a proteome-scale TPD platform and applying it to uncover the time-resolved human protein essentialome, 2) interrogating the interactions between hundreds of therapeutic target proteins and thousands of protein degradation effectors in order to identify new strategies for induced-proximity therapeutics, and 3) characterizing a therapeutic landscape of cancer cell reprogramming strategies in which the function of cancer-associated proteins are overwritten by an endogenous effector protein. This proposal introduces new technologies for high-throughput programmable protein perturbation and induced proximity, offering insights into essential proteins, strategies for cancer treatment based on induced-proximity pharmacology, and a transformative methodology enabling broad applications in biology and medicine.
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 DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
- medical and health sciences basic medicine pharmacology and pharmacy
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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)
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Topic(s)
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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-2025-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.
8092 Zuerich
Switzerland
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.