Paul Hardin (born September 14, 1960) is an American scientist in the field of chronobiology and a pioneering researcher in the understanding of circadian clocks in flies and mammals. Hardin currently serves as a distinguished professor in the biology department at Texas A&M University. He is best known for his discovery of circadian oscillations in the mRNA of the clock gene Period (per), the importance of the E-Box in per activation, the interlocked feedback loops that control rhythms in activator gene transcription, and the circadian regulation of olfaction in Drosophila melanogaster. Born in a suburb of Chicago, Matteson, Illinois, Hardin currently resides in College Station, Texas, with his wife and three children.
Academic career
Hardin earned his B.S. in biology at Southern Methodist University (SMU) in 1982. He then continued to pursue a Ph.D in genetics from Indiana University in 1987 with William H. Klein. He went on to conduct his postdoctoral research at Brandeis University under the supervision of chronobiologist Michael Rosbash. From 1991 to 1995, Hardin worked as a professor at Texas A&M University, and from 1995 to 2005 at the University of Houston. Since 2005, Hardin has worked as a professor and researcher in the biology department at Texas A&M University. He teaches courses on introductory biology, molecular cell biology, and a graduate level class on biological clocks. He also serves as the director of the Texas A&M's Center for Biological Clocks Research and as faculty for the Texas A&M Institute for Neuroscience and PhD program in genetics. In addition, Hardin was also actively involved in the Society for Research on Biological Rhythms; he served as the secretary in 2006, treasurer in 2010, and president in 2016.
Research
Discovery of per mRNA cycling
In 1971, Ron Konopka, a geneticist at the California Institute of Technology, discovered the Period gene, which he found to be involved in the circadian clock of Drosophila. In 1999, Paul Hardin discovered that per mRNA underwent strong circadian oscillations by exposing isolated wild-type per mRNA to a series of light-dark (LD) cycles followed by cycles of constant darkness (DD). As a post-doctorate in the lab of chronobiologist Dr. Michael Rosbash, Hardin specifically noted that per mRNA levels in Drosophila brains fluctuate about 10-fold in a typical 24-hour light-dark cycle. Hardin further demonstrated that wild-type protein, PER, can rescue rhythmicity in the mRNA of an arrhythmic mutant of the per gene. His findings suggested that feedback of the PER protein regulates levels of per mRNA. Hardin ultimately published his seminal work on the rhythmic nature of per mRNA in Drosophila in the journal Nature. This discovery led Hardin and other prominent members in the field of chronobiology to develop a model that describes the clock mechanism in Drosophila. This model is referred to as the Transcription Feedback Loop, which suggests that the translated protein provides negative feedback on the mRNA transcription of itself.
Role of the E-box in per activation
In 1997, Hardin, with Haiping Hao and David Allen, analyzed the sequence of the per gene in Drosophila and found a 69-bp enhancer upstream of the gene. This enhancer sequence contained an E-box (CACGTG), which was determined to be necessary for high-level per transcription. As E-boxes are typically bound by proteins containing a basic helix-loop-helix (bHLH) protein structural motif, the presence of an E-box in per led to the hypothesis that the proteins involved in circadian rhythms may contain a bHLH domain. This proved to be vital in establishing the function of the previously discovered CLOCK protein, which was known to play a role in circadian rhythms and contained a bHLH domain as well. This discovery also aided in the identification of the BMAL1 and CYCLE proteins as critical players in the circadian rhythms of mammalian and Drosophila circadian systems respectively.