Opening up the world of lipids

Mention "lipids" and fats come to mind. Many of us perceive lipids as something bad -- something that will make us fat. They are indeed fatty compounds -- but they are essential components of every cell membrane. There are at least a few thousand forms of human cell lipids and scientists are only now discovering more about them, particularly about their role as "gatekeepers" in the body's important chemical reactions. Lipids coordinate the movement of substances in and out of cells, taking on crucial roles in the reception of signals in the body.


At NUS, a team specialising in lipidomics led by Assoc Prof Markus Wenk, Department of Biochemistry and Department of Biological Sciences, is looking into the roles of lipids and the intriguing mechanisms involved. He believes their work will have a key role in understanding and controlling important diseases. For example, working with the Novartis Institute for Tropical Diseases, his team is looking at tuberculosis (TB) and other diseases where the invading bacteria masquerade as a normal body cell by using its own lipids to enter the host cell.

"The critical role of lipids in cell, tissue and organ physiology is demonstrated by a large number of genetic studies and by many human diseases involving the disruption of lipid metabolic enzymes and pathways. Examples of such diseases include cancer, diabetes, neurodegenerative and infectious disorders," said Assoc Prof Wenk.

However, due to the complexity of lipids and the lack of powerful tools for their analysis, we still do not know enough about lipids, said Assoc Prof Wenk. "The explosion of information in the fields of genomics and proteomics has not been matched by a corresponding advancement of knowledge in the field of lipids," he said.

"Lipids can go through drastic changes and stimulate the cell to do different things, including how it communicates and reacts. Lipids are a critically important class of metabolites. Yet many functions of lipids remain poorly understood, in particular at the molecular level," he added.

Still, progress has been made. In recent times, lipid research has gained from a number of recent achievements and developments. Genetic and cell biological research has provided new insights into molecular mechanisms of lipid action. "It is becoming increasingly clear that deregulated lipid metabolism plays an important role in many human diseases and novel tools for lipid detection are being developed at a very rapid pace," said Assoc Prof Wenk.

As lipidomics is a discipline which, due to its focus on lipids, is intrinsically allied with many other fields of research, Assoc Prof Wenk advocated that a multi-disciplinary approach be taken in this research.

Assoc Prof Wenk said one of their foci would be to research novel approaches in global analysis of lipids for applications in the development of drug and biomarker for various diseases. "We aim to develop novel tools for lipid research which go far beyond current trends in biochemical lipidomics and to apply these approaches to biomedical and environmental research. These tools include hardware (chemical probes, antibodies) as well as software (search algorithms, analytical methods). We will include two prominent areas of R&D focus in Singapore -- immunology/infectious diseases and ageing/neurodegeneration."

His research project is one of the four projects in NUS to be given a generous grant from the National Research Foundation. The project is built on basic research and engineering with a strong outlook on applications. Six laboratories from NUS form the core team. Each member brings in unique expertise and research excellence in a highly integrated approach, merging facets of medicine, cell/biology, bio/engineering, and organic chemistry.

Included as industry partners, the Novartis Institute for Tropical Diseases and instrument manufacturer Applied Biosystems -- will collaborate in development and application of the above tools. The programme will enhance international connections to major initiatives at partner universities, ETH Zurich via the Swiss initiative in systems biology, Systems.X.ch, as well as Yale.