The Ellison Medical Foundation has selected Associate Professor in Pharmacology Jochen Buck to receive a Senior Scholar Award in Aging. The Ellison Foundation supports basic biomedical research concerning aging, the understanding of aging processes, and age-related diseases and disabilities. It is hoped that the Ellison awards will lead to break throughs in the prevention or amelioration of age-related debilitation and disease through an understanding of their biological processes.
Dr. Buck, in collaboration with Dr. Lonny Levin (also a faculty member in the Department of Pharmacology,) has been studying the role of Soluble Adenylyl Cyclase (sAC), a unique enzyme in the maturation processes of mammalian sperm. Drs. Buck and Levin hypothesize that this enzyme may be an essential factor in other mammalian physiological systems such as salt and pH regulation in the kidney, brain, and general metabolic regulation. They plan to test these hypotheses to determine how the activity of sAC might effect the life span of mice. If these hypotheses are correct, this basic research could lead to novel drugs that increase longevity in humans.
For fifty years, researchers have been interested in how signaling happens inside cells. In the 50's, Dr. Earl W. Sutherland, Jr. (Nobel Prize, 1971) discovered cAMP (adenosine 3',5'-monophosphate,) the first intracellular signaling molecule. CAMP, one of the most ancient signaling molecules, is present in organisms from bacteria to man and has multiple signaling functions within cells. Ten years ago, the first mammalian enzymes producing cAMP (Adenylyl cyclases) were characterized and cloned. These enzymes were transmembrane protein (tmAC) which restricted their localization to the cell membrane. Researchers quickly discovered that cAMP had a myriad of effects in the cell which were not easily explained by the transmembrane form of the enzyme. This became most clear in the case of sperm. The cAMP signaling cascade is responsible for the activation of the sperm during ejaculation. This activation is characterized by increased motility and maturation of the sperm so that it can fertilize the egg. The perplexing result concerning sperm adenylyl cylcase was that the enzyme was soluble, which was not consistent with a transmembrane protein. This sperm cyclase, therefore, represented a novel form of adenylyl cyclase.
Dr. Buck's Research
Six years ago, Drs. Buck and Levin, asked the question: What is this novel adenylyl cyclase in sperm? The gene they cloned from protein purified from rat testis had little similarity to the known class of enzymes making cAMP, but a lot of similarity to more ancient enzymes characterized in cyanobacteria. After the gene was cloned, Dr. Buck began asking how this unique enzyme, Soluble Adenylyl Cyclase (sAC) is regulated. It was well established that sperm are activated by bicarbonate (baking soda). During ejaculation, sperm are mixed with high amounts of bicarbonate. One year ago Dr. Buck discovered that sAC was directly activated by bicarbonate. SAC is poised to sense cellular metabolic changes via alterations in CO2 which is the end product of the cellular energy producing pathways. In cells, CO2 is immediately converted to bicarbonate ion, the activator of sAC. Activation of sAC produces cAMP which is regulating metabolic key enzymes.
It is a longstanding observation that caloric restriction in higher and lower species increases longevity. With the support of the Ellison award, Dr. Buck's lab will study whether sAC has a role in this phenomenon.
Lorraine Gudas, M.D., Chair of the Department of Pharmacology, calls Buck "a spectacular researcher." "We're very excited for him. Dr. Buck has discovered an entirely new signaling pathway in cells. With the support of this Ellison award, he will probably continue to produce exciting and novel findings in the area of the molecular basis of aging."
A year ago Center research pilot grant recipient Dr. Jay Edelberg, who coordinates the Center's translational seminars in aging research series, received a New Scholar Ellison Award in Aging. Dr. Buck is the first Weill Cornell faculty member to receive the prestigious and competitive four-year Ellison Senior Scholar Award.