Ronald J. Konopka (1947-2015) was an American geneticist who studied chronobiology. He made his most notable contribution to the field while working with Drosophila in the lab of Seymour Benzer at the California Institute of Technology. During this work, Konopka discovered the period (per) gene, which controls the period of circadian rhythms.
Academic career
Ron Konopka received his Ph.D. in Biology from the California Institute of Technology in 1972. In 1975, following his discovery of the period mutants, Konopka was awarded a faculty position at the California Institute of Technology. While there, Konopka's colleagues were critical of his reluctance to publish his work on the period gene, and Konopka was denied tenure. After his stay at Caltech, Konopka accepted a position at Clarkson University but was again denied tenure and subsequently exited the field of science. Konopka's career, interwoven with the work of his mentor, Seymour Benzer, and the other scientists working in Benzer's lab is narrated in Time, Love, Memory by Jonathan Weiner.
Konopka's discovery and genetic analysis of period and several other circadian rhythm mutations became the basis of the research done by Drs. Jeffrey C. Hall, Michael Rosbash, and Michael W. Young, who were awarded the 2017 Nobel Prize in Physiology or Medicine.
Research
Period mutants
Discovery of Period
As a graduate student in Seymour Benzer's lab, Konopka sought to use Benzer's method of behavioral genetics to unravel the mysteries of the "master clock" that existed in every organism. He used ethyl methanesulfonate (EMS) to induce point mutations in the Drosophila melanogaster genome, and eventually isolated three mutants with abnormal rhythms in eclosion. He mapped the mutations to the same location on the far left of the X chromosome, less than 1 centimorgan away from the white gene locus. These mutations were alternative alleles of a gene that Konopka subsequently named period. While wild type flies have a circadian period around 24 hours, Konopka found the per01 mutant was arrhythmic, the perS mutant had a period of 19 hours, and the perL had a period of 29 hours.
Neurobiology of per mutants
In 1979 and a 1980, Konopka and Dominic Orr tested whether mutations in per mutations affected the period of the entire circadian cycle or just a portion of it. By comparing the light responses of perS eclosion rhythm to that of wild type flies, Konopka and Orr found that light pulses reset the mutant clock to a greater extent than the wild type clock (about 10 hours for perS compared to 3 hours for wild type flies). They also observed that the while duration of the light-sensitive part of the day (subjective night) was found to be similar between perS and wild type flies, the duration of the light-insensitive part of the cycle (subjective day) was 5 hours shorter in mutant flies than in wild type flies. They concluded that differences in period length between mutant and wild type flies could be accounted for by a shortening of the subjective day, or the active part of the circadian cycle, in perS mutants. From this, Konopka concluded that separate molecular processes correspond to the subjective night and subjective day and that the perS allele acts by shortening the subjective day while leaving the subjective night unchanged. Based on these findings, Konopka and Orr constructed a model for the action of the per gene. The oscillation is interpreted in terms of a membrane gradient that is established during the subjective day and dissipates during the subjective night. The model predicts that the per gene product is active during the subjective day and functions like a pump to establish the gradient. Once a high threshold is reached, the pump shuts off and light-sensitive channels open to dissipate the gradient. A light pulse during the subjective night closes the channels and starts the pump; the value of the gradient when the channels close is the same as the value when the pump starts, and thus a reset in the cycle is produced and an oscillation results. This model has been replaced with a transcription translation negative feedback model involving timeless, clock, and cycle.