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Characterisation of high altitude metabolic phenotype driven by unique Andean ge...

Characterisation of high altitude metabolic phenotype driven by unique Andean genetics. High-altitude hypoxia is a known physiological stressor. Genetic signals associated with high-altitude adaptation have been identified in populations native to this environment, yet the links to molecular/physiological processes a... ver más

31/10/2023

THE CHANCELLOR MAS...

272K€

Presupuesto del proyecto: 272K€

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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

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2023-10-31

MSCA-IF-2019: Individual Fellowships Objective:The goal of the Individual Fellowships is to enhance the creative and innovative potential...

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4 Participantes

THE CHANCELLOR MASTERS AND S...

271.73K€ | Lider

ALBATROS, SL

522.55K€ | Participante

THE REGENTS OF THE UNIVERSIT...

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Duración del proyecto: 43 meses Fecha Inicio: 2020-03-24
Fecha Fin: 2023-10-31

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 272K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto High-altitude hypoxia is a known physiological stressor. Genetic signals associated with high-altitude adaptation have been identified in populations native to this environment, yet the links to molecular/physiological processes affording protection against hypoxic stress, specifically those related to metabolic function, remain largely unknown. Conversely, a significant proportion of Andean highlanders develop chronic mountain sickness (CMS), characterised by excessive erythrocytosis and cardiometabolic dysregulation. I will combine genotype analysis, RNA sequencing, cardiopulmonary exercise testing, metabolic/lipidomic profiling and mitochondrial function analyses to study high-altitude Andeans with and without excessive erythrocytosis, in order to identify underlying differences in (mal)adaptive (patho)physiology. Applying methods developed by the partner host laboratory, I will examine pre-selected candidate gene variants along with skeletal muscle metabolic phenotype, probed through assessment of mitochondrial capacity for substrate metabolism. Metabolomic/lipidomic analysis of muscle and plasma alongside measures of whole-body exercise performance will demonstrate the impact of these functional changes in vivo. This multidisciplinary approach will explore the links between adaptive genetic polymorphisms and molecular/physiological processes affording protection against hypoxic stress. It has the potential to further our understanding of the individual metabolic responses to hypoxia by distinguishing healthy adaptive signals from disease-related signatures, and link genetic, metabolic and whole-body physiological function data in the context of CMS. It will provide a foundation for addressing fundamental questions concerning human evolution whilst improving our understanding of highly prevalent hypoxia-related conditions and the metabolic aetiology of these.

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