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All organisms have evolved ways to store energy- mostly as fat packaged into lipid droplets. Farese and Walther explain how lipid droplets form in cells and the physiological importance of getting this process right.

All life requires metabolic energy but energy supplies and demands change over time. For this reason, organisms have developed ways to store energy, predominantly as fat. Neutral lipids are packaged into lipid droplets, small organelles found in most eukaryotic cells and in some prokaryotes. Lipid droplets play a critical role in an organism’s physiology; too many lipid droplets can result in obesity and too few in metabolic disease. In their first video, Drs. Farese and Walther introduce us to lipid droplets and explain their importance in cellular biology.

In Part 2, Walther and Farese explain in more depth how lipid droplets form in cells in an organized manner. Triglycerides and other neutral lipids are made in the ER membrane. They accumulate in localized regions of the membrane that grow towards the cytosol and eventually bud off into lipid droplets. Farese and Walther describe experiments from their lab and others that have identified a protein complex in the ER membrane called LDAF1/Seipin that regulates where triglycerides localize and grow into mature lipid droplets.

In their final talk, Walther and Farese explain how proteins are targeted specifically to the surface of lipid droplets. This has functional consequences since proteins at the surface of lipid droplets govern lipid droplet growth and hydrolysis, and some of these proteins are associated with diseases. Farese and Walther end their talk by describing a number of diseases or physiological conditions that are now recognized as resulting from mutations in genes encoding proteins involved in lipid droplet formation.

Speaker Biographies:
Since 2014, Drs. Robert Farese and Tobias Walther have run a joint research lab in the TH Chan School of Public Health (HSPH) and Harvard Medical School at Harvard University. Their lab studies the mechanisms and physiology of lipid synthesis and storage in lipid droplets; organelles that are vital for storing energy and membrane building materials for the cell.

Robert Farese Jr.:
Farese is currently Chair and Professor of Molecular Metabolism at HSPH, Professor of Cell Biology at Harvard Medical School, and an Associate Member of the Broad Institute. As an undergraduate student at the University of Florida, Farese studied chemistry. He went on to do an MD degree at Vanderbilt University. He completed his residency training at the University of Colorado and then moved to the University of California, San Francisco to train in endocrinology and metabolism. From 1994-2014, Farese was an investigator at the Gladstone Institutes at UCSF. In 2005, he took a sabbatical in the lab of Peter Walter at UCSF. There he met Tobi Walther, who was a post-doc at the time, and they began their long-running collaboration to study lipid droplets.

Farese has received numerous awards and honors for his pioneering research. He is an elected member of the American Society for Clinical Investigation and the Association of American Physicians and he has received the Bristol-Myers Squibb Freedom to Discover Award and the ASBMB Avanti Award in Lipids.

Tobias Walther:
Walther was a PhD student at the European Molecular Biology Lab (EMBL) where he studied the nuclear pore. He then moved to Peter Walter’s lab at the University of California, San Francisco for post-doctoral studies. It was during his stay at UCSF, that he began his long-time collaboration with Bob Farese to study lipid droplets. Following his post-doc, Walther led labs at the Max Planck Institute of Biochemistry in Martinsreid and then at the Yale School of Medicine. In 2014, he and Farese set up their joint lab at HSPH.

Walther is currently a Professor of Molecular Metabolism at HSPH, Professor of Cell Biology at Harvard Medical School, an Associate Member of the Broad Institute and an Investigator of the Howard Hughes Medical Institute. For his contributions to research in lipid metabolism, Walther received the ASBMB Walter A. Shaw Young Investigator Award in Lipid Research in 2013.

Learn more about research in the Farese and Walther Lab here:
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