In early May 2010, I was fortunate to be able to attend and present a poster entitled 'Development of high-throughput platforms for the study of drug-membrane interactions' at the LIPID Metabolites and Pathways Strategy (LIPID MAPS) Annual Meeting, which took place in Scripps Seaside Forum, San Diego, USA. The LIPID MAPS initiative seeks to identify and quantify all lipids and their interacting moieties in mammalian cells (namely the 'lipodome'), using sophisticated techniques such as mass spectrometry, in order for the scientific community to begin to understand how these molecules play a part in various lipid-based disease mechanisms, including diabetes, stroke, and cancer.
The conference had an intense and varied programme with over 20 keynote speakers presenting their research in two days. The six sessions spanned a variety of areas that looked at membrane-protein interactions, cell and tissue imaging and roles of lipids in inflammatory disease and cell biology. The session on metabolomics, clinical networks and informatics was predominantly concerned with the proposal of pooling various external bodies, with the goal of better understanding and elucidating mechanistic pathways in disease states, eg neurodegenerative disease.
It was proposed that different networks ought to link with one another and act in a collaborative manner, specifically the metabolimics network, which Dr Rima Kaddurah-Daouk described, with the lipidomics and genomics networks. However in order to fulfil such a task, particularly from the lipidomics point of view, it is apparent that an efficient way in which to categorise and organise the vast amount of lipid data needs to be utilised.
Dr Stephen Bryant, from the National Centre for Biotechnology Information, talked about PubChem's contribution to the LIPID MAPS project over the last few years; all natural lipid structures have been incorporated into the database, of around 20,000 records, and are now encouraging researchers to utilise the additional features of PubChem, which include the citation of 'Bioassays', and lipids' roles in biochemical pathways. In unison, the bioinformatics core has developed a novel lipid classification system – this consists of a unique molecular identifier for each lipid molecule, incorporating the chemical skeleton, any stereochemistry, degree of unsaturation and charge.
The 55 posters on display covered a wide variety of areas, and I particularly valued a paper by Dr Francis Szoka of the University of California San Francisco, on the topic of sterol-modified phospholipids (SMLs), which is applicable to my own research. The Szoka group have synthesised a novel family of SMLs, where cholesterol is chemically attached to a glycerophospholipid molecule, ie its chemical motif consists of cholesterol substituted at either the sn-1 or -2 position in place of an aliphatic tail.
Interestingly it has been observed that the biophysical properties of the chimeric form of cholesterol behave in a similar manner to that of free cholesterol. Although the immediate application of SMLs by the Szoka group is concerned with enhanced liposomal drug delivery, where SML-doped liposomes are highly resistant to contents leakage due to the enhanced liposome stability associated with a reduction in cholesterol exchange with biomembranes, such lipid molecules are of great interest to anyone conducting studies of a biophysical nature on model membranes. Consequently, SMLs could be of great use in the field of droplet-interface bilayers (DIBs), a technology used in my own PhD studies for interrogating drug-membrane interactions.
DIBs are formed simply by bringing together two or more aqueous droplets in an oil environment where lipids are present. As the lipid molecules stabilise the aqueous-oil interface, a bilayer (or 'DIB') is formed as a result of the two monolayers coming into close proximity. If, for example, one would wish to produce cholesterol-containing DIBs, hence aligning the complexity of the lipid content towards that of more biologically relevant mammalian membranes, one may foresee potential problems associated with cholesterol demixing into the oil phase. SMLs therefore provide an opportunity to interrogate DIBs comprising cholesterol-containing lipid mixtures in model membrane systems.
In summary, this conference has provided me with a wealth of knowledge, enabling me to learn more about the LIPID MAPS project and the wider scientific community to further my research. Additionally it has presented itself as an excellent networking opportunity, providing me with an opening to meet and discuss my research with high profile/prestigious leaders in the field of traditional lipidomics and biophysical and biomedical fields. It was very inspiring to have so many people interested in my research and provide me with feedback and suggestions for the future.
I would therefore like to thank SCI for providing me with the opportunity to attend this conference.
Claire Stanley, Imperial College London
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