Objective
Chronic inflammatory diseases, such as, for example, asthma, afflict millions of people worldwide. Nevertheless, the molecular mechanisms that drive inflammation remain poorly understood. Enzymes play a crucial regulatory role in inflammation and represent potential drug targets. Nevertheless, the activities of these enzymes are poorly studied due to a lack of convenient tools for modulation and detection. The importance of this issue is demonstrated by my previous work on small molecule probes for protein palmitoylation. It becomes increasingly clear that the slow advance in the development of chemistry-based methods to study enzyme activity in its physiological context delays drug discovery.
To address this problem further, I will develop novel detection methods and small molecule inhibitors to study inflammatory signal transduction pathways. Protein acetylations at lysine residues have a broad regulatory scope. Acetylations of histones form a major part of the histone code for epigenetic regulation of gene-transcription. In addition, reversible acetylations of non-histone proteins proved to be crucial for regulation of nuclear factor kB (NF kB) mediated gene transcription.
I aim to study the role of acetylations of histones and other proteins in NF kB mediated gene transcription. Firstly, I will develop a novel bioorthogonal ligation strategy for chemical labeling of protein acetylation in cells (aim 1) by employing the oxidative Heck reaction. Secondly, I will be the first to systematically investigate changes in protein acetylation in response to activation of the NF kB pathway using a proteomics strategy (aim 2). Thirdly, I will develop small molecule inhibitors of acetyltransferases and study their impact on acetylations that regulate the NF kB signaling pathway (aim 3).
Ultimately, these newly developed detection methods and small molecule inhibitors open up opportunities for drug discovery aimed at epigenetic regulation of NF kB mediated inflammation.
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.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- medical and health sciences clinical medicine pneumology asthma
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences health sciences inflammatory diseases
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.
ERC-2012-StG_20111109
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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.
Host institution
9712CP Groningen
Netherlands
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.