Objective
A large body of evidence suggest that reversible post-translational modifications (PTMs) of histones play a crucial role in gene expression and to the field of epigenetics, and that aberrant histone modification contributes to different diseases such as cancer. Recently, two novel types of histone PTMs called lysine malonylation (Kmal) and succinylation (Ksucc) have been identified. KMal and Ksucc induce more substantial chemical changes to the chemical properties of the modified protein than lysine acetylation or methylation, which are already known to have very important cellular roles. Taking into account the fact that most previously described histone PTMs have important biological functions and are implied in different human diseases, a logical hypothesis is that Ksucc and Kmal also play an important role in the regulation of histone protein structure and function, and potentially also across the wider proteome. These novel PTMs open many interesting questions:
• Which histone lysine residues are the targets for these novel PTMs?
• What enzymes regulate addition (writer) or removal (eraser) of Kmal and Ksucc?
• Are there reader proteins that bind to histone Kmal and Ksucc to modulate changes in gene transcription?
• What role do histone Kmal and Ksucc play in the regulation of histone structure and function?
However, there are no standard and robust tools to directly identify and manipulate the enzymes or binders, and identifying the targets is currently a massive undertaking, and it is not easy to ‘pulse-chase’ without a label. The aim of the proposed project is to develop a platform of chemical probes and technologies that will enable for the first time proteome-wide global analysis of the complex biological network involve in these new types of PTMs of histone. These novel chemical biology tools will be used to identify novel histone targets and the enzymes (writers and erasers) and proteins (readers) involved in these new PTMs.
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
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences genetics epigenetics
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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.
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.
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.
FP7-PEOPLE-2012-IEF
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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.
Coordinator
SW7 2AZ London
United Kingdom
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.