A research paper on the gene regulating the circadian rhythm that Professor of Biology Kathy Siwicki worked with a team on a research project about the gene regulating the circadian rhythm. On Oct. 2, this research won the Nobel Prize.
The paper, titled “Antibodies to the period gene product of Drosophila reveal diverse tissue distribution and rhythmic changes in the visual system,” was carried out by five researchers.
Siwicki and the others were studying a gene in fruit flies that regulates the circadian rhythm, which are endogenous biological rhythms that most organisms have. They are biological “clocks” that regulate the timing of an organism’s behavior and physiology so that it coordinates with the day-night cycle.
According to Siwicki, in this particular gene (called the period gene) that regulates behavioral rhythms, the protein that the gene produced had its own daily rhythm. Levels would increase during the night and decrease during the day, even in the darkness. They concluded that the differing levels were not a reaction to light.
This finding led to development of a model for how the circadian clock works through changes in the expression of the gene, which was originally proposed around 1990. It explained not just fruit flies’ circadian clocks but all organisms’ circadian clocks through the same mechanism. All animals have period genes; humans have three.
“We were studying fruit fly clocks because it was a fascinating biological puzzle, not because we necessarily wanted to solve the puzzle of the human circadian clock … we didn’t know it at the time, but the mechanism we were studying in fruit flies laid the groundwork for understanding human circadian clocks as well,” Siwicki said.
They were hopeful that the mechanisms in fruit flies would be relevant to the understanding of the human circadian clock as well as those of other animals and plants. Siwicki believes that the surprising homology and similarity between the clocks of various organisms is part of the reason that her research is being recognized. The connection between a gene and a behavior is a “complex biological puzzle” that hadn’t really been worked out for hardly any genes in the 1980s.
“There was no road map for how to do this. We were taking it one step at a time, using whatever methods were available to us at the time,” she said.
There were two different labs working on the research at the same time and were led by Jeffery C. Hall and Michael Rosbach, two of the Nobel laureates. The two groups collaborated closely, though there was competition between them. The third lab, run by the third Nobel laureate, Michael Young, was at Rockefeller University. The competition between the groups contributed to the progress, mentioned Siwicki.
“We just had to work as hard as we could to get data and produce evidence that would give us insights and try to get to the finish line before they did,” Siwicki said. “The competition influenced the intensity of our efforts.”
However, Siwicki still emphasized the value of working collaboratively with other people.
“It’s a combination of hard work and intense intellectual engagement with the problem that is more fun when you’re doing it as a team,” she said.
One thing Siwicki tells former students is that she did this recognized work when she was in her early thirties, and the people leading the lab (Nobel laureates) were in their early forties. According to her, scientists get the opportunities to make important discoveries when they’re relatively young. All of her former students who are in their early thirties are in a prime position to make their own discoveries.
“There are still big, challenging questions about the connection between genes and complex behavioral phenotypes, including neurological and clinical disorders that still need to be worked out,” Siwicki said.
Chair of the Biology Department Elizabeth Vallen emphasized Siwicki’s commitment to mentoring students and supporting their success.
“Kathy has been instrumental in promoting neurobiology and neuroscience in the department … she’s just been an incredible mentor and role model, who for a long time has been continually committed to teaching and having a research program in areas that are… competitive,” Vallen said.
She used to teach a seminar about circadian rhythms, and she has transitioned to do more work related to behavior, particularly learning and memory, Her interest is the neurobiology of behavior.
Her current research program on learning and memory was actually brought to her as an idea by a student from one of her seminars. She works with students at different levels, and is open to new ideas about what kinds of research would work well at Swarthmore.
Siwicki has been invited to attend the award ceremony held by the Nobel organization in Stockholm on December 10, where the project will be recognized.
“I have no words. It’s exciting and thrilling,” she said. “I kept saying that I feel like my head is going to explode because it was a feeling that I’ve never had before.”