RESEARCH

Lipids are essential components of living systems; they are key chemical constituents of cells accounting for ca. 50% of cellular mass. At a subcellular level, the vast majority of lipids are associated with membranes where they have a well-recognized structural role. In addition, lipids also occur in the form of lipids droplets, enriched in neutral lipids that serve as a key storage reservoir for cellular energy substrates. Further, specific species of membrane lipids (eg:sterols, sphingolipids) are thought to underpin the compartmentalization of membranes into nanoscale assemblies along with proteins. At a molecular level, membrane lipids can regulate the activities of embedded proteins either allosterically or via protein lipidation. In addition, a range of low abundance lipids and their metabolites (eg: phosphoinositides) can function as intracellular messengers to regulate key cellular processes such as membrane turnover, cytoskeletal organization as well nutrient uptake and biosynthetic processes. Additionally, in the context of metazoans, lipid derived molecules (eg: steroid hormones) secreted into extracellular space serve as chemical messengers to co-ordinate the function of various tissues.

Finally qualitative and quantitative changes in the levels of various lipids have been implicated in disease states; these include well-recognized monogenic lipid storage disorders (eg: mucolipidosis) as well as polygenic conditions such as obesity, Type II diabetes mellitus and atherosclerosis.

Although the major classes of cellular lipids have been known for over a hundred years, the complexity of the cellular lipid pool is increasingly becoming clear. For each of the major classes and sub-classes of lipids, a large numbers of unique species have been described. Each of these species contain fatty acyl chains with a unique carbon chain length as well as differing levels of desaturation, i.e double bonds. Variations also occur on the lipid class determinant/head group (eg varying numbers of phosphorylations on the inositol head group of phosphoinositides). Taking these modifications into account, it is suggested that in an eukaryotic cell, the so-called “lipidome” may consist of thousands of individual lipid species. With the availability of analytical methods of increasing sensitivity and sophistication increasing numbers of lipid species are being described.

Despite the large number of lipid species that have been described, much less is know about their function as well as the biological relevance of their relative abundance. Further there are only a few studies (mainly for signaling lipids) that have been able to link cellular activity mechanistically with specific cellular processes at a molecular level. Work at the Lipid Center will address these questions using a multidisciplinary approach.

By analyzing the complete set of lipids from different cells and organisms, we aim at developing the necessary tools to make lipidomics an integral part of biological systems analysis. This is the challenge that the Indo Max Planck Partnership between the MPI of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden and the National Centre of Biological Science (NCBS) in Bangalore aims at taking up. Focused on Lipid Research, the Partnership aims at combining the existing expertise in both Institutes to maintain a leading role in the structure and function of cellular membrane as well as metabolic processes and become centers for lipidomics worldwide. To achieve these aims, the Partnership in addition requires strong chemical synthetic support. Thus, other Institutes of the MPG that are successful in the field of lipid chemistry (i.e. MPI of Colloids and Interfaces in Potsdam-Golm, Germany) or chemical companies and institutions located in Bangalore and elsewhere in india will be involved. It is widely accepted that lipids play a pivotal role in host-pathogen interactions and infection processes. Therefore, integrated in this Partnership will be institutes in Germany and India that are working infectious diseases where the study of lipids will have a particular impact on both science and society (i.e. MPI of Infection Biology in Berlin).

Goals     
To perform a systematic analysis of the lipidome in a set of living organisms.     
To identify biochemical pathways leading to the production and degradation of lipids.     
To identify role of particular lipids in the organization and function of the membrane of subcellular compartments, cells, tissues and a organism as a whole.