A new award from the National Science Foundation may help researchers at the Virginia Bioinformatics Institute unlock the secrets of the body's internal clock.
The $750,000 award will aid research on circadian rhythms' effects on fundamental cellular processes that, when altered, result in the development of numerous diseases and disorders, including cancer. The award will also provide educational opportunities for high school students from Virginia and Argentina.
Circadian rhythms, often referred to as the body's internal clock, interest researchers for their broad-ranging impacts on human health.
These mechanisms are responsible for more than eating and sleeping; they also aid in proper functioning of the cell cycle and in helping the cell respond to environmental conditions. If circadian rhythms are disrupted and environmental signals are adverse or poorly interpreted, the decision of a cell to live, divide, or die can be compromised. Diseases ranging from cancer to neurodegenerative disorders could arise as a result.
"We're just beginning to understand the big picture of how the environment influences the cell's decisions here," said Carla Finkielstein, an associate professor in the College of Science, the project's principal investigator, and a fellow at the Virginia Bioinformatics Institute. "What we thought we knew about the functioning of circadian rhythms has revealed itself to be one small part of a large and intricate puzzle."
In previous research, Finkielstein and her team were able to pinpoint a causal relationship between the transcriptional regulator Human Period 2 and a tumor suppressor protein, hp53. The group's research provides evidence that disruptions in circadian rhythms play a critical role in tumor genesis and progression.
One common obstacle to healthy circadian function is prolonged exposure to artificial light.
If the light-dark cycle is altered, as in shift work where people are awake at night and asleep during the day, their circadian rhythms can be disrupted, which can in turn throw off hormonal cycles, metabolic cycles, and neurotransmitter rhythms. Such disruptions can even, as Finkielstein's team has shown, cause tumor growth by interrupting normal tumor suppressing factors, such as the key DNA damage repair component, hp53.
Shift workers like nurses, custodians, and security guards are particularly susceptible to this kind of disruption, as their circadian rhythms are constantly thrown off by the nature of their work. For example, increasing evidence points to rising incidences of breast cancer cases reported among shift workers.
With input from the fields of mathematical modeling, bioengineering, and biochemistry, Finkielstein and her team hope to establish how circadian rhythms control cellular checkpoints that allow cells to develop and slough off as they normally should, and how certain environmental stresses, like altering the body's physiology by shift work, perturb the system. By using mathematical modeling to understand the smaller pieces of the puzzle, the larger picture of circadian rhythms will emerge. Ultimately, the goal is to learn how to manipulate these rhythms for optimal health.