A new tool enables biomedical researchers from around the world to quickly see the connections between lipids and proteins inside cells, thanks to a new initiative led by scientists at Oregon Health & Science University.
Scientists say the new open-access database and dashboard could accelerate new treatments involving an understudied but potent aspect of human health.
"Lipids are involved in nearly every aspect of cell biology and play central roles in diseases including infection, stroke, heart attack, cancer, neurodegeneration and immune disorders," said Fikadu Tafesse, Ph.D., professor and chair of microbiology and immunology in the OHSU School of Medicine. "Pretty much every component of cellular function is connected to lipids and lipid metabolism."
Researchers describe the new "lipid interactome" in a study published online on Feb. 18 in the journal Bioinformatics. Gaelen Guzman, Ph.D., of OHSU is the first author.
Once thought to be passive membranes akin to microscopic walls in and around cells, scientists have come to realize in recent decades that lipids play a much more active role in biology. Not only do lipids store energy within the cells — some 50,000 distinct types of lipids have been identified so far — but scientists have increasingly come to realize lipids play a complex role in signaling within between cells.
This is where the new interactome may be crucial in unlocking their greatest potential in developing new vaccines and medications.
Scientists describe the new interactome as a type of "Google maps" charting the interplay between lipids and proteins. OHSU scientists say bringing together a vast database that logs interactions between the innumerable types of lipids and proteins may be the crucial step toward understanding how lipids drive disease.
"We know the biochemistry of some lipids, but we don't always know their role in cell maintenance and shape," said Carsten Schultz, Ph.D., professor and chair of chemical physiology and biochemistry in the OHSU School of Medicine. "This may be because they bind to certain proteins in the cell."
Every cell molecule in the body is made up of four components: proteins; nucleotides that form DNA and RNA; carbohydrates; and lipids.
Schultz noted that massive databases already have been assembled by the National Institutes of Health in the United States and the European Bioinformatics Institute in the United Kingdom describing the connections between proteins as well as connections between proteins and nucleotides. A single living database housing the connections between lipids and proteins has been sorely lacking, until now.
"This is a science community-building tool," Schultz said. "it's a credit to the collaborative scientific rigor of the research conducted at OHSU and with many colleagues around the world to have something like this based here."
Lipids remain a crucial but underappreciated aspect of scientific discovery partly because classifying and manipulating distinct lipids is excruciatingly difficult.
Schultz and scientific collaborators recently developed a set of chemical toolkits capable of manipulating the membrane's signaling and sometimes even its biophysical properties. The toolkit uses light to manipulate lipid membranes and thereby help scientists better understand how lipids influence cell shape and cell division — a critical aspect in cancer, for example.
"Lipids function together with proteins to accomplish their biological role in the cell," Tafesse said. "We want to identify the proteins that interact with lipids to do their thing because this translates the lipid world into the much better-known protein world. This is particularly useful in viral infections where the infected cell is vastly changing its lipid composition. The database will help scientists around the world perform this research.."
The research was supported by funding from the National Institute of Allergy and Infections Diseases, of the National Institutes of Health, award number R01AI141549; and the National Institute of General Medical Science of the NIH, award numbers R01GM127631, and R01GM151682.
