FWGDEKKER

Novel tools to read and write the epigenetic code in inflammation

 Coordinatore RIJKSUNIVERSITEIT GRONINGEN 

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 Nazionalità Coordinatore Netherlands [NL]
 Totale costo 1˙500˙000 €
 EC contributo 1˙500˙000 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2012-StG_20111109
 Funding Scheme ERC-SG
 Anno di inizio 2012
 Periodo (anno-mese-giorno) 2012-12-01   -   2017-11-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    RIJKSUNIVERSITEIT GRONINGEN

 Organization address address: Broerstraat 5
city: GRONINGEN
postcode: 9712CP

contact info
Titolo: Dr.
Nome: Dick
Cognome: Veldhuis
Email: send email
Telefono: 31503634142
Fax: 31503634500

NL (GRONINGEN) hostInstitution 1˙500˙000.00
2    RIJKSUNIVERSITEIT GRONINGEN

 Organization address address: Broerstraat 5
city: GRONINGEN
postcode: 9712CP

contact info
Titolo: Dr.
Nome: Frans Jacobus
Cognome: Dekker
Email: send email
Telefono: 31503638030

NL (GRONINGEN) hostInstitution 1˙500˙000.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

inflammation    nevertheless    drug    molecule    acetylation    detection    regulation    enzymes    small    pathway    epigenetic    acetylations    transcription    gene    proteins    crucial    nf    discovery    kb    inflammatory    poorly    protein    inhibitors    strategy    mediated    histones    regulatory    histone   

 Obiettivo del progetto (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.'

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