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HeartAtaK

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Targeting the Anti Target From Structure to Drug in the heart Kv11.1 channel

Potassium channels are widely distributed and have many important biological functions in the human body. Of special interest is the Kv11.1 channel, whose main function is the repolarization of the membrane after a cardiac action... ver más

31/08/2018

UNIVLEEDS

183K€

Presupuesto del proyecto: 183K€

Líder del proyecto

UNIVERSITY OF LEEDS 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 H2020 notifico la concesión del proyecto el día 2018-08-31

MSCA-IF-2015-EF: Marie Skłodowska-Curie Individual F...

I+D

Cerrada hace 9 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

UNIVLEEDS

183.45K€ | Lider

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Duración del proyecto: 29 meses Fecha Inicio: 2016-03-16
Fecha Fin: 2018-08-31

Líder del proyecto

UNIVERSITY OF LEEDS No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 183K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Potassium channels are widely distributed and have many important biological functions in the human body. Of special interest is the Kv11.1 channel, whose main function is the repolarization of the membrane after a cardiac action potential. Unfortunately, this channel can be blocked by a variety of structurally diverse drugs causing the long QT syndrome (LQTS), a cardiac repolarization disorder that can lead to arrhythmia and sudden heart death. Due to this very severe side effect, a variety of drugs with otherwise good therapeutic profiles have been withdrawn from the market. Nowadays, cardiac Kv11.1 is an important anti-target in drug development to exclude any potential side effects that could lead to LQTS. In contrast, tumour cells require the expression of specific isoforms of Kv11.1 for survival making these channels a potential anti-cancer drug target – as long as these drugs do not bind to the heart isoform. The major goal of this project is the elucidation of the structure of Kv11.1 via X-ray crystallography or cryo-EM. I have established large-scale protein production of a Kv11.1-chimera using the baculovirus/insect cell expression system, thus enabling biophysical and structural studies to provide structural information on a range of time- and spatial resolution scales. This will not only shed light on the structural motifs responsible for binding a variety of structurally diverse drugs but also improve the fundamental knowledge for the understanding of the special biophysical properties of this channel. By taking these techniques together I will be able to determine how known inhibitors bind, and so identify new isoform specific binding pockets to guide isoform-specific drug design. My career goal is to pursue fundamental and translational research in structural biology of human membrane protein, with a focus on medically important targets and further drug development. This project will bring me closer to that goal.

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