Keri L. Colabroy - US grants

The Muhlenberg College Departments of Biology, Chemistry, and Mathematics and Computer Science are jointly integrating bioinformatics into multiple biology and biochemistry courses at three levels: introductory, intermediate, and advanced. There are two major educational goals for this project: 1) to improve undergraduate sophistication about bioinformatics, and 2) to increase the mathematical content in the biology and biochemistry curricula. The project is serving approximately 200 biology, biochemistry and neuroscience majors each year. One introductory biology course, three intermediate level biology laboratory courses, and three advanced courses in biology and biochemistry are introducing new bioinformatics components or are expanding and improving existing components. Laboratory curricula feature multiple-week investigative experiences that build on existing experimental schemes. The curricular goals are being supported by a new genomics and proteomics core laboratory facility that features real-time PCR and 2-D gel electrophoresis. In addition, multiple laptop computers are enabling students in introductory and upper-level courses to work on challenging problems in smaller discussion sections and laboratories. The new computers allow instructors to explore computational applications, and the underlying mathematics, more effectively in the classroom. Faculty development, in the form of a one-time week-long inter-disciplinary on-site bioinformatics course, is supporting the curricular goals, inspiring faculty in the use of the new technology, and encouraging collaboration among biologists, biochemists, and computational scientists. The increased faculty expertise and interdisciplinary collaboration is also resulting in undergraduate research projects in bioinformatics or projects that rely on bioinformatics as an integral tool within the research design.

Intellectual Merit: The project adapts and implements published curricular suggestions for improving undergraduate education in biology and bioinformatics. The over-arching mission is to educate more quantitatively-literate biology students. Faculty development, the potential for new collaborations in courses and student research, and the new laboratory core facility itself are having a significant impact on the local science environment. The value of bioinformatics as a tool for improving quantitative instruction and the specific instructional schemes themselves are being assessed through student surveys and other instruments as appropriate.

Broader Impact: Familiarity with basic bioinformatics and computational approaches is increasingly a necessity for professionals in a range of areas related to the life sciences. The assessment of curricular outcomes from the project is being disseminated broadly to provide a reference point for the development of similar strategies and projects at other undergraduate institutions.

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Keri Colabroy from Muhlenberg College and Dr. Larryn Peterson of Rhodes College to investigate an unstudied family of enzymes that cleave ring-shaped molecules called catechols. Catecholic rings are found in the woody tissue of plants to provide structure and strength. Nature refashions these rings into antibiotics and other bioactive materials. The complex relationship between enzyme structure and function is not well understood. This lack of understanding limits the ability to exploit the use of enzymes to make new natural products and degrade plant material into biofuels. The researchers generate new knowledge through the collaborative study of the enzyme-catalyzed reactions in real-time using small molecules carefully designed to expose the inner workings of catalysis. In addition to the direct mentorship of undergraduate students in faculty research labs, students transfer between institutions to experience the project from different perspectives. Part of the project is integrated into undergraduate coursework at each of the home institutions to give additional undergraduates the opportunity to conduct original research. Instructional videos of the established and emerging technologies and methods used in this research are published to a freely-accessible, online research archive for training of the next-generation science, technology, engineering and mathematics workforce both at the partner institutions and beyond.

This research project expands understanding of the extradiol dioxygenase mechanism by exploring structure and function for evolutionarily distinct, but representative members of a discreet topology (type IV) group within the vicinal-oxygen-chelate (VOC) superfamily. The synthesis of novel small-molecule substrates fuel the study of reaction kinetics, both in the pre-steady state and at equilibrium. This work also uses X-ray crystallography and mutagenesis to define the roles of active site residues and global kinetic modeling of substrate and mutant data to develop a mechanism. These experiments broaden the structural and kinetic understanding of extradiol dioxygenase mechanism, while also providing the opportunity to understand the extent of conservation versus permutation of dioxygenase mechanism as a function of topology within the VOC enzyme family.