Project description
Custom-built proteins to outsmart cancer
Transcription factors, the proteins that switch genes on and off, are the cell’s master regulators. When they malfunction, they can trigger uncontrolled cell growth, leading to cancer. Scientists are studying how these proteins are regulated and how to stop them when they go wrong. In this context, the ERC-funded ProTailor project aims to study how subtle chemical changes, known as post-translational modifications, affect gene activity. To do this, it will build customised versions of transcription factors. Using cutting-edge chemistry and molecular tools, the project seeks to map how these tweaks drive cancer. The findings will open the door to smarter, more precise therapies in the future.
Objective
The aberrant function of oncogenic transcription factors (TFs) is one of the most common drivers in human cancers, yet the mechanisms underlying their deregulation and targeting remain elusive. Understanding pathways that regulate TFs function has the potential to develop novel therapeutic compounds to target tumorigenesis. The overreaching goal of ProTailor is to develop ground-breaking modified TFs to understand gene expression regulation mechanisms and set the foundation for therapeutic opportunities to study and target human tumorigenesis.
Aim 1: I will develop novel synthetic strategies to prepare site-specifically modified oncogenic TF analogs bearing defined post-translational modifications (PTMs) to decipher the molecular role of PTMs in regulating gene expression. I will combine chemoselective peptide ligation, and orthogonal transformations, along with high-throughput screening to probe the molecular role of essential PTMs on gene recognition, interaction, and cancer-related oncogene expression.
Aim 2: I will generate libraries of chromatinized-DNA probes to investigate the interactions of modified TFs with packed DNA, aiming to understand how PTMs modulate TF-DNA interactions, accessibility, and influence gene expression regulation. I will probe the crosstalk between TF-PTMs, epigenetic modifications, and chromatin binding sites to unravel the mechanisms underlying gene recognition and interactions.
Aim 3: I will design photoreactive TF probes to map the regulatory role of PTMs in the interactions of oncogenic TF analogs with transcriptional machinery. I will deliver the synthetic TF probes to cancer cells and dissect the mechanisms by which PTMs modulate biomolecular interactions and unravel potential PTM markers associated with oncogene expression.
ProTailor will provide novel and powerful research tools to understand gene expression regulation mechanisms and lay the groundwork for therapeutic strategies to investigate and target human tumorigenesis.
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
- 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)
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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
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-STG
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69978 Tel Aviv
Israel
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