Melting into thin air: Hypoxia, muscle wasting & genetic variation

With a reduced oxygen supply, humans show wasting and loss of muscle mass. This occurs in aging-associated pathophysiological conditions (i.e. chronic obstructive pulmonary disorder [COPD], ~14 % of >65 years of age), a RCUK research priority, or in high-altitude exposure in healthy lowlanders. Muscle atrophy is predictive of mortality, independent of disease symptoms, and prevention of atrophy offsets mortality. My research group studies myostatin, a central regulator of muscle mass (Elliott et al. 2012). Whist others demonstrated COPD patients have elevated myostatin, we directly demonstrated myostatin expression is altered by hypoxia alone. However, Tibetans, Sherpa and Highlander Peruvians exist in chronic hypoxia without muscle loss. What advantageous adaptations do these people carry?

The doctoral candidate will characterise the response of individuals born at high altitude (Tibetan Plateau) and lowlander individuals to hypoxic stresses. Muscle and endocrine markers of muscle atrophy will be matched against predetermined haplotype differences between populations. In the second part of this project, key genes identified in part one will be silenced in muscle cells in vitro. Modified and control cells will have their hypoxic response characterized to see if this produces a cellular ‘highlander’ phenotype.

The doctoral candidate will spend time embedded in the research laboratory of Dr Tatum Simonson, University of California San Diego, to gain necessary molecular and genetic skills (Simonson et al., 2010, 2015). This candidate will thus gain expertise in molecular and translational clinical physiological skills, and master in vivo and in vitro laboratory techniques. The candidate will take part in the University Graduate School and Faculty Doctoral Research Development Programme; in addition to these training programmes and skills listed above, the student will gain important transferable skills to aid future career progression. The candidate will be encouraged to join The Physiological Society and The Endocrine Society to aid academic development.