A consortium of researchers is going to identify and discover interactions of all lipid metabolites in macrophages.
The five-year, $35 million grant from the National Institute of General Medical Sciences (NIGMS) will support more than 30 researchers at 18 universities, medical research institutes, and companies across the United States, who will work together in a detailed analysis of the structure and function of lipids. The principal investigator of this collaboration is Edward Dennis, Ph.D, professor of chemistry and biochemistry in UCSD’s Division of Physical Sciences and UCSD’s School of Medicine.
Dennis notes that while sequencing the human genome was a scientific landmark, it is just the first step in understanding the diverse array of systems and processes within and among cells. Establishment of this consortium is a significant step in an emerging field called “metabolomics,” or the study of metabolites, chemical compounds that “turn on or off cellular responses to food, friend, or foe,” he explained.
Lipids are a water-insoluble subset of metabolites central to the regulation and control of normal cellular function, and to disease. Stored as an energy reserve for the cell, lipids are vital components of the cell membrane, and are involved in communication within and between cells. For example, one class of lipids, the sterols, includes estrogen and testosterone.
The initial phases of the project, known as Lipid Metabolites And Pathways Strategy (LIPID MAPS), will be aimed at characterizing all of the lipid metabolites in one type of cell. The term “Lipidomics” is used to describe the study of lipids and their complex changes and interactions within cells. Because this task is too extensive for a single laboratory to complete, researchers at participating centers will each focus on isolating and characterizing all of the lipids in a single class. This information will then be combined into a database (at http://www.lipidmaps.org) to identify networks of interactions amongst lipid metabolites and to make this information available to other researchers. Shankar Subramaniam, Ph.D., professor of chemistry and bioengineering at UCSD’s Jacobs School of Engineering and San Diego Supercomputer Center, will coordinate this aspect of the project.
The cell type selected for study is the macrophage, best known for its role in immune reactions, for example scavenging bacteria and other invaders in the body. Macrophage cells from mice will be used, rather than human cells, because there exists a “library” of mouse cells with specific genetic mutations. By studying cells missing certain genes, the research team will attempt to identify what genes code for those enzymes key in synthesis and processing of lipid metabolites. Christopher Glass, M.D., Ph.D., professor of cellular and molecular medicine at UCSD’s School of Medicine, will coordinate the macrophage biology and genomics aspects of the consortium.
What is interesting about this project is that it typifies a trend in biological sciences toward the more systematic and thorough collection of information on all the parts of each subsystem or category of cellular metabolism. Systematic efforts to collect data on cellular metabolites and components will provide the raw data needed to construct of far more detailed models of cellular metabolism. Coded up as computer programs these models will eventually be able to predict how each imaginable intervention in cellular metabolism will affect all the subsystems in a cell and in the larger organism that the cell is part of. Computer models built with sufficient detail will allow simulation runs to a serve in place of laboratory experiments that currently require real cells and real organisms. The systematic collection of data on the subsystems and components of cells will therefore lead to a great acceleration in the rate of biological science and in biological engineering.
Update: In another sign of the times the LIPID MAPS project has been made possible by instrumentation advances.
The LIPID MAPS project has become possible thanks to the refinement of mass spectrometers, which determine the type and quantity of lipids in a mixture. Today, machines can identify hundreds of lipids in a sample simultaneously using electron spray ionization mass spectrometry. Particles are fired at lipid molecules to chisel off shards, the chemical structures of which are determined one by one.
The development of better instrumentation does more to accelerate the rate of advance in biology than any other factor.
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