HISTONE DEMETHYLASES

A Chemical Genetics Approach towards Cancer Therapy Targeting Histone Demethylases

 Coordinatore THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD 

 Organization address address: University Offices, Wellington Square
city: OXFORD
postcode: OX1 2JD

contact info
Titolo: Ms.
Nome: Gill
Cognome: Wells
Email: send email
Telefono: +44 1865 289800
Fax: +44 1865 289801

 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 200˙371 €
 EC contributo 200˙371 €
 Programma FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call FP7-PEOPLE-2011-IEF
 Funding Scheme MC-IEF
 Anno di inizio 2012
 Periodo (anno-mese-giorno) 2012-03-01   -   2014-02-28

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

 Organization address address: University Offices, Wellington Square
city: OXFORD
postcode: OX1 2JD

contact info
Titolo: Ms.
Nome: Gill
Cognome: Wells
Email: send email
Telefono: +44 1865 289800
Fax: +44 1865 289801

UK (OXFORD) coordinator 200˙371.80

Mappa


 Word cloud

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

molecule    specifically    synthesis    enzyme    chemical    special    cancer    dna    demethylases    biology    cell    enzymes    gene    groups    small    therapy    histones    pairs    certain    histone    marker    inhibit   

 Obiettivo del progetto (Objective)

'Cancer is one of the most common causes of death in the EU. The disease is characterized by aberrant gene activity in certain cells. Even today, cancer therapy is little focused, which is reflected by severe side effects. Consequently, there is a need for novel and better tolerated therapies. In this proposal an approach to validate a new class of enzymes as targets for cancer therapy is presented. In the cell nucleus, DNA is bound to special proteins, called histones, which play key roles in gene regulation. Histones can be dynamically modified with special marker groups, which allows the control of gene expression without alteration of the DNA itself. Specifically, it is intended to inhibit histone demethylases, specialized enzymes which remove certain marker groups (methyl groups) from histones, which results in gene silencing or activation. Histone demethylases are known to be upregulated in certain cancers and are therefore promising candidates for pharmacological cancer therapy. Ideally, small molecule inhibitors will inhibit cancer growth and might even be able to restore the normal genetic program of a cell. During the study specific small molecule-enzyme pairs will be created, which allows the study of a single enzyme among very similar ones. This chemical genetics approach encompasses the mutation of the enzyme and the synthesis of specifically tailored small molecules. The properties of the enzyme-inhibitor pairs will be evaluated by in vitro assays and crystallization. Afterwards the compounds will be used to decipher the role of the histone demethylase in cell culture models by microarray methods and RNA sequencing. The study will be very interdisciplinary and encompass chemical synthesis, biochemistry, cell biology and structural biology.'

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