Mitochondrial DNA methylation in human disease
Mitochondrial science is one of the fastest growing fields in genetics and clinical studies, connecting research areas ranging from early embryo development to ageing. Found in every cell type in the human body with the exception of red blood cells, mitochondria are the ‘powerhouses of the cell’ that generate the majority of the adenosine triphosphate (ATP) required for cellular processes and perform many other metabolic tasks, including signalling through mitochondrial reactive oxygen species, regulation of membrane potential, apoptosis-programmed cell death, calcium signalling, regulation of cellular metabolism, steroid synthesis and hormonal signalling. Alterations in mitochondrial metabolism are known to play a role in many human diseases including neuronal diseases, metabolic syndrome (including insulin resistance, hypertension, abnormal lipid levels, impaired glucose tolerance, and diabetes), and cardiovascular disease.
Epigenetic marks, particularly DNA methylation, are essential for normal cellular function, including embryonic stem cell differentiation, X-chromosome inactivation and parental-dependent allelic imprinting. They are also implicated in many human diseases and cancers, and are known to be disrupted through ageing, stresses, viruses, exposure to air particle pollutants, diet/nutrition, and cancers. Mitochondria contain their own DNA, a genome of approximately 17 kb in circular form, and recent studies have demonstrated that mitochondrial DNA can be methylated by machinery existing inside of the mitochondria in a similar way to the nuclear genome. This epigenetic modification can mediate the control of mitochondrial gene expression, and it is disrupted in neurodegenerative diseases and cancers.
My research interests in this emerging field are the processes by which the mitochondrial epigenome is regulated and how it is implicated in health and disease. I have shown that mitochondrial DNA methylation is affected by exposure to airborne pollutants, including pre-natal exposures, and my recent pilot work has demonstrated that it is disrupted in cardiovascular disease. I am also interested in the development of novel technologies to study the mitochondrial epigenome.
The project available in my laboratory aims to understand the role of mitochondrial epigenetics in obesity and cardiovascular disease, and how dietary intervention may impact upon mitochondrial DNA methylation through regulation of mitochondrial DNA methyltransferases. The work will involve use of a range of technologies, including pyrosequencing, whole epigenome sequencing, q-PCR, in vitro cell culture and general molecular works. We use human specimens and an in vitro system for our research.