Project Reference: TRG27-PDN-DG1

Project title: Early Origins of Heart Disease in an Embryonic Model of Obstructive Sleep Apnoea During Development

Project outline

Obstructive sleep apnoea (OSA) is characterised by episodes of intermittent hypoxia (IH), which promote oxidative stress and increase the risk of heart disease in patients. In turn, human pregnancy is associated with OSA, which is aggravated by obesity, the rates of which in the UK, including in women of reproductive age, are reaching pandemic proportions.  Therefore, the chance of an embryo or fetus being exposed to IH of the type that may occur with OSA in pregnancy is now very real.  Despite this, the effects of IH on the developing cardiovascular system are unknown.  Therefore, this PhD project will study the effects of IH using the chicken embryo, an established model system that permits isolation of the direct effects of challenges and therapy on the developing cardiovascular system, independent of effects on the mother and/or the placenta.

Fertilised chicken eggs will be exposed to normoxia or IH to mimic moderate OSA in human pregnancy (21% and 10% FIO2, 40 cycles h−1 for 12 h day−1 (Oxycycler, BioSpherix). At day 19 of the 21-day incubation period, hearts will be isolated.  In one cohort, the heart will be mounted onto a Langendorff preparation to determine effects on systolic and diastolic function during basal conditions and in response to ischaemia-reperfusion (IR).  Other cohorts of embryos will be perfusion fixed at term to determine cardiac wall remodelling and cardiomyocyte number, size and nuclearity.  A final cohort of embryos will be reserved for freezing hearts at term to determine signalling pathways by molecular biology and miRNA analysis.  The PhD project will include identifying interventional strategies, including treatment with mitochondria-targeted antioxidants, such as MitoQ.  Data will also determine differences depending on the sex of the embryo.  The successful candidate will join an active laboratory full of support by ECR supervisors experienced in teaching vulnerable research skills in cardiovascular physiology.

Principal Supervisor

Professor Dino Giussani

Email address: dag26@cam.ac.uk

Department / Partner Institute: Physiology, Development and Neuroscience (PDN)

Website: https://www.pdn.cam.ac.uk/directory/dino-giussani

BBSRC strategic theme

Understanding the rules of life