Richard Hendler received his M.A. in physiological chemistry at the University of Pennsylvania in 1949 and his Ph.D. in biochemistry at the University of California at Berkeley in 1952. He came to the NIH in 1952 as a fellow of the National Foundation for Infantile Paralysis. From 1954 to 1955, he was at the University of Brussels, Belgium as a Special Research Fellow of the U. S. Public Health Service. Dr. Hendler joined Dr. Christian Anfinsen’s laboratory in the NHLBI in 1955 working in the area of protein synthesis. He retired as head of the NHLBI’s Section on Membrane Enzymology in 2000, but continued to work as a volunteer. In 2002, he was named a Scientist Emeritus. He currently pursues his research both at the NIH and The Institute for Bioscience and Biotechnology Research at the National Institutes of Standards and Technology. He is a member of the American Society for Biochemistry and Molecular Biology, Biophysical Society, Phi Beta Kappa, Society of Sigma Xi, Pi Mu Upsilon, Alpha Epsilon Delta, and Phi Eta Sigma. Dr. Hendler was awarded an NIH Award of Merit, “For development of mathematical processes for deconvolution of a complex spectrum into individual components and a spectrometer for rapidly recording sequential spectra.” This linear algebraic approach based on Singular Value Decomposition is widely used throughout the world for a variety of different applications. In addition to his numerous scientific manuscripts, Dr. Hendler is the author of the book, “Protein Biosynthesis and Membrane Biochemistry,” first published in 1968.
Energy-driven proton pumps are of major importance for living systems. Organisms from microbes to humans rely on specialized proteins that use photon energy or electron transfer to form an electrochemical gradient from proton movement, which is then used to synthesize ATP. Specific details, at the atomic level, on how these pumps transduce energy through the transport of protons across biological membranes are lacking. Dr. Hendler is focused on learning more about the structural changes and mechanism of action of energy-driven proton pumps, using bacteriorhodopsin (BR) as a model system. BR is a relatively simple, light-activated proton pump found in Archaea, but information obtained from this protein could help in understanding more complex systems such as mammalian cytochrome oxidase.
Dr. Hendler’s research has successfully combined visible and infrared (IR) spectral/ kinetic approaches to follow the path of protons across the cell membrane and the extent of protein conformational change at each step of the transduction process. Through these studies, his laboratory has identified the most important intermediate step for converting the input photon energy into a transient transmembrane voltage used to form ATP, as well as provided evidence to support the view that the BR transduction consists of two parallel cycles instead of the single photocycle that is favored by many researchers.
Recently, Dr. Hendler has been developing procedures to study single crystals of BR protein and characterize their kinetic behavior using his laboratory’s visible and IR approaches. His ultimate goal is to combine these techniques with time-resolved X-ray diffraction of BR membrane crystals to obtain atomic-level structural information of the protein conformational changes that result in the electrogenic transport of protons across the membrane.
During the course of his BR studies, Dr. Hendler has developed new linear algebra based mathematical techniques for isolating absolute visible and IR spectra of intermediates and better defining the kinetic sequence of events. The idea occurred that these techniques might be useful in unraveling the kinetic steps of plaque formation in Alzheimer’s disease (AD). In AD development, amyloid beta monomers are polymerized through a number of steps to oligomers, fibrils, and eventually plaques. Recent research has suggested that one of the soluble oligomeric forms of amyloid, and not the large fibrils or plaques, trigger the resulting pathology in AD. Dr. Hendler is currently testing to see if his approaches might identify the guilty oligomer.