A grant has been awarded to Dr. Steven James and Dr. Kazuo Hiraizumi, co-principal investigators at Gettysburg College, to procure two major items of equipment through the Major Research Instrumentation Program of the NSF. A computerized system that integrates photodocumentation with image analysis and a preparative ultracentrifuge will allow the two faculty and their students to conduct research that cannot be executed with the equipment currently available at Gettysburg College. The goals of this grant are to expand the scope and quality of training in molecular and cellular biology for undergraduates. Gettysburg College provides a research-intensive learning environment for undergraduates in the sciences. Experiential, hands-on learning is encouraged by requiring student-faculty collaborative research for the B.S. degrees in Biology and Biochemistry/Molecular Biology (BMB). Students in these degree programs write a research prospectus, spend at least a full semester on their research, write a scientific paper on their work that is evaluated by faculty, and present their research to their peers during an end-of-semester colloquium. All BMB majors are required to conduct individualized research and over 60% of Biology majors choose the B.S. track; a substantial number of these students go on to graduate school. The instrumentation procured with NSF support will allow undergraduates working with Drs. James and Hiraizumi to perform cutting-edge research, thereby giving them excellent preparation for graduate school and careers in science.
The focus of Dr. James' research is the regulation of the cell cycle, a carefully orchestrated series of events that coordinates chromosome replication with nuclear and cell division. Dr. James studies the role of genes that regulate this process, using as a model system the bread mold Aspergillus. The focus of Dr. Hiraizumi's research is population and evolutionary genetics of gene regulation. He studies genes that code for a group of digestive enzymes called peptidases, using the fruit fly Drosophila melanogaster. Both faculty employ techniques of molecular genetics, cell biology, and biochemistry in their research. In these fields, a most fundamental question involves the relationship between the DNA sequence of a gene and the function of the protein that it encodes. Mutations in the sequence of DNA often cripple or destroy the resulting protein, which can produce devastating effects. To understand the relationship between DNA sequence, protein function, and the physiological effects of mutations requires sophisticated instrumentation for isolating molecules and measuring their activity. First, the ultracentrifuge provided by support from this NSF-MRI grant will enable isolation of large amounts of maximally pure DNA and protein. This preparative ultracentrifuge subjects particles or molecules to high centrifugal force and separates them based on differences in their density, size or shape. Second, the photodocumentation /image analysis system will be used to measure the activity of both normal and mutant proteins. These proteins will be isolated and purified using the ultracentrifuge, or by a different technique called gel electrophoresis. Gel electrophoresis separates molecules through a gel matrix subjected to electrical current. DNA can also be separated in this manner. To detect and measure the molecules of interest, they are chemically stained or radioactively labeled. The resulting signals are stored as electronic files, which can be analyzed for quantitative differences with a high degree of sensitivity and precision. This helps to determine which genes are turned on under various conditions, how much of the protein is present, and whether there are differences in the activity of a protein between genetically different individuals.
The research conducted by these faculty and their students addresses questions that have potential medical applications. For example, many genes that regulate cell division can undergo mutation that leads to cancer. In all organisms, cell division is governed by a similar set of genes. Thus, investigating the regulation of genes that control cell division in a simple, easy-to-study model organism such as Aspergillus aids in understanding the molecular and cellular processes leading to cancer in more complex, less tractable organisms such as humans. Recently, scientists discovered surprising similarity in the DNA sequence of human and fruit fly genes. A mutation in a peptidase-coding gene could produce debilitating effects, such as a form of neuronal ceroid lipofuscinosis, a fatal hereditary neurodegenerative disease in humans. The use of the fruit fly peptidases as a model provides information on how mutations affect the physiological function of these enzymes in other organisms, including humans. Thus, with support from the NSF-MRI grant, Gettysburg College undergraduates will benefit from expanded opportunities to perform modern research on relevant biological problems. These experiences will in turn prepare them for graduate studies in molecular and cellular biology and careers in biomedical research.