Student research project
Supervisor: Professor Peter Meikle
he Metabolomics Laboratory uses state-of-the-art tandem mass spectrometry to obtain metabolic/lipid profiles from cell and animal models in addition to clinically relevant human samples to develop new approaches to diagnosis, risk assessment and therapy for diabetes and cardiovascular disease.
Plasmalogens are glycerophospholipids present in numerous tissues that can act as a natural antioxidant1. Modulation of plasmalogens can be achieved with oral administration of their metabolic precursors, naturally occurring compounds known as alkylglycerols. Plasmalogen modulation has reported to suppress diseases related to oxidative stress such as atherosclerosis2. However, the capacity of plasmalogen modulation to attenuate different aspects of metabolic disease is not fully defined and our understanding of the mechanisms involved is limited. Obesity and insulin resistance are forms of metabolic disease that involve dysregulation of lipid metabolism, heightened oxidative stress and chronic inflammation. Lipidomic profiling of multiple populations and clinical cohorts has identified decreased levels of plasmalogens to be associated with aging and obesity3 as well as pre-diabetes and type 2 diabetes4.
We hypothesise that upregulation of plasmalogens will reduce oxidative stress, improve the lipid dysregulation that accompanies obesity, suppress inflammatory responses, and ameliorate insulin resistance associated with metabolic disease.
The specific aims are to:
- Define the potential of plasmalogen upregulation as a therapeutic approach against obesity induced metabolic dysfunction.
- Define the role of plasmalogens in metabolic disease by genetically altering biosynthetic and catabolic pathways of plasmalogens in a tissue specific manner.
This project is suitable for an Honours or PhD student and will combine our lipidomics and lipoprotein expertise with our established mouse models of insulin resistance and oxidative stress and new genetically altered mouse models of tissue specific plasmalogen modulation to define both the potential and the mechanisms of plasmalogen modulation. Definition of the mechanisms operating to attenuate disease pathogenesis will provide a clear rationale for the subsequent translation and commercialisation of this new prophylactic therapy.
- Functions of plasmalogen lipids in health and disease Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2012;1822(9):1442–52.
- Plasmalogen modulation attenuates atherosclerosis in ApoE-and ApoE/GPx1-deficient mice Atherosclerosis 2015;243(2):598–608.
- Plasma lipid profiling in a large population-based cohort Journal of lipid research 2013;54(10):2898–908.
- Plasma lipid profiling shows similar associations with prediabetes and type 2 diabetes PloS one 2013;8(9):e74341.