Lubert Stryer, professor emeritus at Stanford University, has spent his research career harvesting the power of light. Some of his most important work has used light to develop tools to explore the structure and function of biological macromolecules. In his recent “Reflections” article for The Journal of Biological Chemistry, Stryer recounts his life experiences and gives praise to many of the students, postdoctoral fellows and collaborators who have helped him produce a successful career. One common thread in his life has been his interest in trying to understand the “interplay of light and life.”
Stryer’s interest in light-catalyzed reactions was first piqued in an introductory biology course at the University of Chicago. Stryer writes in his “Reflections” essay that he can “vividly recall my excitement on seeing this graphic demonstration of key features of photosynthesis in a test tube.” Conversations with Nobel laureate James Franck, an emeritus professor in chemistry at the University of Chicago, were just as important to his career path. Stryer worked as a waiter during his time at the university, and Franck was a frequent customer who always ordered the same thing. This left ample time for conversations about science. Stryer and Franck discussed Franck’s initial research on energy transfer, which revealed that excitation energy can be transferred through direct electromagnetic interaction. At some point, Franck told Stryer, “One day, you too might work on energy transfer.” This, in fact, turned out to be the case.
Stryer’s first foray into studying fluorescence energy transfer came when he was a summer research student under Douglas Smith at Argonne National Laboratory. Smith introduced Stryer to photodynamic action, a process whereby light activates a photosensitizing dye in the presence of oxygen, leading to cellular damage. At Smith’s urging, Stryer read the literature about Theodor Förster’s theory of energy transfer. Stryer was intrigued by the theory’s prediction of the absolute dependence on the distance of the two dipoles. Stryer viewed this as a potential way to develop new knowledge of biological macromolecules using energy transfer in proteins.
Stryer entered medical school at Harvard University under the mentorship of Elkan Blout. He performed research investigating polyglutamic acid and polylysine complexation with dyes and effects on optical rotation. Stryer devoted his career to basic research during his fourth year in medical school. Blout planned Stryer’s postdoctoral research career, making sure Stryer boned up on his physics, chemistry and mathematics, and then Stryer headed off to the Medical Research Council Laboratory in Cambridge, England. It was an exciting time for Stryer, and he says his years in the two Cambridges were some of the best in his life.
Stryer’s independent research career began at Stanford University. One of his major accomplishments there came while investigating how fluorescence energy transfer can serve as a way to measure the distance between two sites in a protein. Using the recently introduced solid-phase peptide synthesis technique, Stryer’s group synthesized a series of polypeptides with chromophores at known distances and determined their transfer efficiencies. Their study demonstrated that energy transfer can serve as a “spectroscopic ruler.” Much of the labeling work that is done today using FRET can be credited to the pioneering work of Stryer.
Another one of Stryer’s significant accomplishments was offering a better understanding of the biochemical basis of visual amplification. Rhodopsin is a photosensitive membrane protein that undergoes a cis-to-trans isomerization in the presence of light. This isomerization starts the cascade of events leading to the eventual firing of the optic nerve and visualization. Stryer and his team were the first to elucidate successfully the components and mechanism of the cGMP cascade responsible for rhodopsin activation.
Stryer has had a number of fruitful collaborations that were born from his interest in light. These collaborations have led to the development of important light-based tools that have moved the field forward and are still in use today. Stryer and researchers from the University of California, Berkley, developed multicolor fluorescent probes conjugated to biological molecules for flow cytometry and fluorescence microscopy. Also, as a scientific adviser to what is now known as Affymetrix, Stryer directed efforts to produce light-activated combinatorial synthesis libraries on a solid support for peptides and oligonucleotides.
Now that Stryer’s research career has ended, he explores his fascination with light in other ways. Since his retirement from Stanford, Stryer has spent much of his time enjoying his two interests: photography and adventure travel. He has traveled to Antarctica, the Arctic, the Galapagos Islands and Africa to take pictures. Although he is retired, science is still on Stryer’s mind. He says, “Photography has heightened my awareness of color in the natural world and deepened my interest in color vision.”
Pumtiwitt C. McCarthy (firstname.lastname@example.org) is a research fellow in the NIH Pharmacology Research Associate Program of the National Institute of General Medical Sciences.