Kathleen K. Siwicki - US grants

The PI has discovered a unique protein that appears to be essential to the biologic clock which determines daily rhythms controlled by the brain. The discovery of the protein came out of work she did at Harvard on the molecular biology of the "period" gene in the Drosophila and its influence on biological rhythms. From this lowly fly brain an exciting generalization has come because the proteins which the Drosophila genes express in neurons are also expressed in the hypothalamus of vertebrate animals. This indicates the vital importance of the gene to brain function as it has been conserved for millions of years. Dr Siwicki will study the neurons in the brain by applying an antibody she has produced to the protein produced by the gene and study the electrophysiology of the identified neurons to test the biological consequence of neurons containing the protein. This should clarify if cells that produce the product are rhythm generators which keep the brain "on time" to coordinate brain function.

The PI has discovered a unique protein that appears to be essential to the biologic clock which determines daily rythms controlled by the brain. The discovery of the protein came out of work she did at Harvard on the molecular biology of the "period" gene in the Drosophila and its influence on biological rhythms. From this lowly fly brain an exciting generalization has come because the proteins which the Drosophila genes express in neurons are also expressed in the hypothalamus of vertebrate animals. This indicates the vital importance of the gene to brain function as it has been conserved for millions of years. Dr. Siwicki will study the neurons in the brain by applying an antibody she has produced to the protein produced by the gene and study the electrophysiology of the identified neurons to test the biological consequence of neurons containing the protein. This should clarify if cells that produce the product are rythm generators which keep the brain "on time" to coordinate brain function.

Lay Abstract PI: Siwicki, Kathleen K. Proposal Number: IBN-9723920 From our own sleep-wake cycle to the chirping of crickets on summer evenings, examples of circadian (daily) rhythms in behavior are abundant in nature. These rhythms are driven by internal biological clocks in the nervous system that are synchronized with the daily cycles of light and temperature in the environment. In the past decade, researchers have deciphered the basic mechanism by which biological clocks keep time: the clock's central gears are genes that turn on and off every day. While rhythmic behaviors and clock genes have been identified in a variety of organisms, the cellular mechanisms by which clock genes produce their behavioral effects are relatively obscure. This project examines the mechanisms by which clock genes act within cells and tissues to produce circadian rhythms of behavior. Experiments allow for direct studies of cells regulating rhythmic behavior and how the properties of those cells are regulated by the clock genes within them. These studies represent a significant step towards understanding the physiological mechanisms by which clock genes and the cells that express them can interact to generate circadian rhythms in behavior.

This award provides partial support for the acquisition of a laser scanning confocal microscope for the college's new Science Center. This will allow faculty and students in the departments of Biology and Engineering to advance the goals of at least six different research projects. Neurobiologists will map the brain circuits responsible for learning and memory in fruit flies in order to improve understanding of how small neural networks can generate complex behaviors. Other research teams will address fundamental questions in developmental biology by visualizing molecules that determine how different cells in a young plant embryo produce different structures, or by asking how cells in a young turtle embryo make the turtle's shell. Cell biologists will attempt to understand how cells divide during the final phase of mitosis by watching the interactions among specific proteins in yeast mutants that divide abnormally. Microbiologists will grow bacterial biofilms and examine them in the confocal microscope in order to understand their formation, structure and sensitivity to ultrasound. In addition, researchers in the Engineering department will use this instrument to probe microscale fluid mechanics, with potential applications to microcoolant systems and other devices.

Because student research is an essential component of the educational mission at this college, these research projects will be conducted with undergraduate students working in close collaboration with their faculty mentors. A comprehensive training program will allow the student researchers to take full advantage of this new instrument. In addition, laboratory exercises involving confocal microscopy will be integrated into intermediate and advanced courses in both the Biology and Engineering departments. As a result of direct experience with the powerful three-dimensional imaging capabilities of this microscope, it is expected that students will more readily grasp the organization of biological structures, and will gain a more tangible understanding of cellular processes in living cells.

This coeducational liberal arts college has an outstanding record of graduates who pursue careers in the sciences. Direct experience with the confocal microscope will contribute to training these young scientists, and will allow them to perform world-class research as undergraduates. Their research projects will advance understanding of fundamental questions in biology such as how cells divide, how cells and molecules in an embryo interact to produce an adult organism, how simple neural networks generate complex behaviors, or how bacteria form potentially hazardous biofilms. A significant impact of this confocal microscope will be to enhance training for the next generation of biologists, teaching them to think integratively about molecular, cellular, and organismal-level processes, and providing them with experience in analytical methods which will be essential tools in their future scientific careers.