Project description
Deciphering transcription factor binding
Transcription factors are of clinical importance because their mutations are often associated with disease and they can be targets of treatment. Understanding why a transcription factor binds to a specific chromatin can lead to enhanced clinical prediction and targeted therapies. However, there is currently no means available to measure the biochemical kinetics of transcription factor binding events. The ERC-funded TF-KINETIX project aims to develop novel proteomics and genomics tools that will measure the regulation of transcription factor binding kinetics to the chromatinised genome. To do so, it will decipher interactome- and genome-wide binding kinetics of three transcription factors associated with lung cancer. It will also design predictive binding models to engineer cell-state-specific transcription factor binding profiles.
Objective
Transcription factor binding is orchestrated by a complex interplay between DNA sequence, chromatin composition, protein interactions, and transcription factor concentration. These regulatory features determine the binding kinetics: how long it takes for a certain amount of transcription factor to associate, and subsequently dissociate from specific binding sites. These kinetics are in turn determined by the thermodynamic properties of each interaction.
It is currently not possible to measure the biochemical kinetics of transcription factor binding across the chromatinized genome inside the nucleus of a cell. To understand why a transcription factor binds to a specific chromatin:DNA-sequence context in a specific cellular state at a specific time, we need to measure how chromatin and DNA influence the biochemical parameters that underpin transcription factor binding. This gap in knowledge limits our functional understanding of why a binding event occurs, and it hampers accurate predictions of transcription factor binding.
Here, I will establish a novel proteomics and genomics toolkit to decipher the regulation of transcription factor binding kinetics to the chromatinized genome. I will resolve interactome- and genome-wide binding kinetics of three lung-cancer-associated transcription factors. By delineating association and dissociation rates, and changes in disorder and binding energy, of all binding events across the genome, I aim to obtain a quantitative understanding of how the proteome composition, epigenetic landscape, and genetic code dictate transcription factor binding. Finally, I will build predictive binding models to engineer cell-state-specific transcription factor binding profiles.
Together, this will transform our knowledge about transcription factor binding into a functional understanding where instead of observing, we understand why each binding event occurs when it occurs, and how we can steer these events.
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 proteomics
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics genomes
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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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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.
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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-2024-STG
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1066 CX AMSTERDAM
Netherlands
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