Seeing Is Believing
Drosophila Embryo at 8 stages of cell division
Lately, Jennifer Lippincott-Schwartz, Ph.D., has a passion for self-renewal—of the cellular variety. Over its lifetime, a single living cell must constantly refine its components by getting rid of old and faulty organelles or proteins. Autophagy (from the Greek, meaning literally “to eat oneself”) is the process that makes possible both this refinement and ultimately, when necessary, controlled cell death.
Electron Microscope image of organelles in a cell
“Cell death, like cell growth, is integral to everything that happens within an organism,” explained Jennifer Lippincott-Schwartz, Head of the Section on Organelle Biology at NICHD. Each of us is composed of roughly 100,000,000,000,000 cells that contain the same basic genetic information. One cell is part of an eye and another is part of a limb as a result of dynamic decision-making processes within individual cells to grow, differentiate, proliferate or die that begin in development and persist throughout life.
Lippincott-Schwartz realized early in her career that to really understand cellular behavior, one needed to study the internal workings of cells over time. Electron microscopy, although a powerful tool for see fine structure, could not depict more than a single moment in time.
Fluorescent labeling of two organelle systems in a single cell
Lippincott-Schwartz first joined the Intramural Research Program (IRP) as a post-doctoral fellow in 1986, and a few years later began using the newly discovered green fluorescent proteins (GFP) to “tag” organelles in living cells and follow their microscopic progress. These studies laid the foundation for the work she continues to this day.
When she started her own laboratory, her post-doctoral fellow, George Patterson, discovered a way to turn GFP into a form that could be switched on by shining a tiny beam of light on the molecules. More recently, she hosted Howard Hughes Medical Institute physicists Eric Betzig and Harold Hess as collaborators in the development of a new super-resolution technique for using photoactivatable GFP to follow the fate of individual proteins. “Eric had developed the theoretical basis, but had neither access to these proteins nor a laboratory in which to build a microscope,” said Lippincott-Schwartz.
Jennifer Lippincott-Schwartz in her lab at NICHD
“It wasn’t just that we added these photoactivatable GFPs and presto we could see super-resolution images,” said Lippincott-Schwartz. The project required everything from a purpose-built microscope and software development to the right techniques for processing the cell samples. “All the expertise we needed was in our Branch.” Their proof-of-principle study was published in the journal Science in 2006.
Lippincott-Schwartz is currently studying organelles that mediate autophagy. Over its lifetime, a single living cell must constantly refine its components by getting rid of old and faulty organelles or proteins. Autophagy makes possible both this refinement and ultimately, when necessary, controlled cell death. Autophagosomes mediate this process.
Single cell expressing a fluorescent marker that targets autophagosomes
Autophagy is increasingly seen to play a critical role in diseases ranging from cancer to neurodegeneration, so understanding the laws that do apply to these specialized organelles is more important than ever. Autophagosomes can apparently form virtually anywhere in the cell, recruited by molecular signals that Lippincott-Schwartz and her team are working to dissect. “We can remove a whole organelle system from a cell simply by manipulating the signals that trigger autophagy. We can actually watch it.”
Jennifer Lippincott-Schwartz, Ph.D., is Chief of the Section on Organelle Biology in the Cell Biology and Metabolism Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).