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TB-IMMUNOGEN

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Understanding genetic control of global gene expression in human macrophages to...

Understanding genetic control of global gene expression in human macrophages to discover new immune mechanisms protecting from tuberculosis Tuberculosis (TB) is a major global problem that urgently requires new preventive and therapeutic approaches. Only minority of people infected with M. tuberculosis develops active TB. Genetic studies provide an unbiased way to sca... ver más

31/12/2015

THE CHANCELLOR MAS...

2M€

Presupuesto del proyecto: 2M€

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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 2015-12-31 No tenemos la información de la convocatoria

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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 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Tuberculosis (TB) is a major global problem that urgently requires new preventive and therapeutic approaches. Only minority of people infected with M. tuberculosis develops active TB. Genetic studies provide an unbiased way to scan the whole human genome to find sequence polymorphisms that predispose to TB. Therefore, we have established the world s largest sample collection for TB genetic studies. Now we genotype 6,000 HIV-negative patients with pulmonary TB and 6,000 healthy controls at ~1 million polymorphic sites across the whole genome. This genome-wide association study (GWAS) will allow us to compare frequency of genetic variants among patients and controls to find genes that protect from TB. Given that susceptibility to TB is a complex disease, a complementary strategy in genetic research is to identify variants that control intermediate cellular phenotypes. Here, for the first time I will undertake a large-scale study to identify polymorphisms that control gene expression in human macrophages, cells that play key role in protection from M. tuberculosis. We will study in vitro global gene expression in uninfected and M. tuberculosis-infected macrophages from hundreds of healthy volunteers correlating it with the genome-wide genotype data of these subjects. This will allow us to identify variants that regulate differential gene expression in macrophages upon M. tuberculosis infection. We will also study functional effects of the polymorphisms associated with TB risk in the previous and ongoing studies. Taken together these experiments will discover genes and biological pathways involved in protection from M. tuberculosis and will characterise macrophage transcription profile of subjects that are genetically predisposed to TB.

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