Project description DEENESFRITPL Genetics of the high altitude metabolism While genetics are associated with high-altitude adaptation in populations native to this environment, the links to molecular and physiological processes related to metabolic function remain largely unknown. It is interesting to note that a significant proportion of Andean highlanders develop chronic mountain sickness characterised by increased erythrocytosis and cardiometabolic dysregulation. The EU-funded Champagne project will employ genotyping, RNA sequencing, cardiopulmonary testing, metabolomics, lipidomics and mitochondrial analyses to study high-altitude Andeans to identify underlying differences in (mal)adaptive (patho)physiology. This multidisciplinary project will explore the links between adaptive genetic polymorphism and mechanisms of protection against hypoxic stress. Show the project objective Hide the project objective Objective 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. Fields of science medical and health sciencesbasic medicinephysiologynatural sciencesbiological sciencesgeneticsRNA Keywords High-altitude hypoxia human evolution chronic mountain sickness genotype-phenotype metabolic (patho)physiology mitochondrial respiration metabolomics lipidomics exercise performance Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2019 - Individual Fellowships Call for proposal H2020-MSCA-IF-2019 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Net EU contribution € 271 732,80 Address Trinity lane the old schools CB2 1TN Cambridge United Kingdom See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all Partner Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement. THE REGENTS OF THE UNIVERSITY OF CALIFORNIA United States Net EU contribution € 0,00 Address Franklin street 1111 12 floor 94607 Oakland ca See on map Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 165 265,92
