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Histone Demethylases

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A Chemical Genetics Approach towards Cancer Therapy Targeting Histone Demethylas...

A Chemical Genetics Approach towards Cancer Therapy Targeting Histone Demethylases 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. Conseque... ver más

28/02/2014

UOXF

200K€

Presupuesto del proyecto: 200K€

Líder del proyecto

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2014-02-28 No tenemos la información de la convocatoria

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1 Participantes

UOXF

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Líder del proyecto

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 200K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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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