Once viewed simply as a reservoir for carbon storage, lipids are no longer cast as bystanders in the drama of biological systems. The emerging field of lipidomics is driven by technology, most notably mass spectrometry, but also by complementary approaches for the detection and characterization of lipids and their biosynthetic enzymes in living cells. The development of these integrated tools promises to greatly advance our understanding of the diverse biological roles of lipids (Wenk 2010 Cell 143:888-895).
Lipid levels are governed by genetics, diet and the environment and lipid metabolism forms a central basis of homeostasis (structure, energy) and communication (cell signalling). Genetic studies in mice have provided insights into alterations in inositol signalling lipids which are compatible with life but which lead to abnormal neuronal function (Cremona et al 1999 Cell 99:179-188; Di Paolo et al 2004 Nature 431:415-422). However, lower and upper boundaries of natural variations in lipid levels are to a large extent unknown. Apolipoprotein E4 is a major risk factor for late onset Alzheimer Disease but variations in ApoE isoforms do not per se affect bulk lipid homeostasis in mouse brain (Sharman et al 2010 J Alzheimers Dis 20:105-111). Comparative lipidomic analysis of brain tissue from animal models and human patients with Alzheimer Disease reveals a multitude of changes as well as some commonalities in different brain regions (Chan et al 2012 J Biol Chem 287:2678-2688). Changes in cholesterol and sphingolipid metabolism are consistent with a view that adaptation in lipid homeostasis during ageing may affect specialized membrane organization and trafficking. Sterol homeostasis was also shown to be correlated with increased risks to Parkinson Disease. Lanosterol, (the first sterol with the characteristic cycloalkane ring structure during biosynthesis of cholesterol, induces mitochondrial uncoupling and protects dopaminergic neurons from cell death (Lim et al 2012 Cell Death Differ 19:416-427).
Research Activities :
Honors and Awards :
- 2009: NUS Yong Loo Lin School of Medicine – Research Excellence Award
- 2009-: LipidomicsNet (European Union FP7) – Scientific advisory board
- 2010 : NUHS Yong Loo Lin School of Medicine – Faculty Outstanding Researcher Award
- 2011-: Rapid Communication in Mass Spectrometry – Editorial board
- 2012 : Knut & Alice Wallenberg Foundation, Scientific reviewer