The goal of this project is to develop an educational program in which undergraduate, graduate, and postdoctoral students learn the process of scientific discovery in the setting of active learning in biology coursework and hands-on experience in the principal investigator's laboratory. The research goal is to elucidate developmental mechanisms that give rise to complex sensory circuitry. The proposed research addresses important themes seen throughout the biology curriculum and will thus be integrated in the educational goal.

Sensory processing relies on neural circuitry that forms during embryonic and postnatal development in very precise patterns. A key question in biology is how these neural circuits form. In order to address this question, one must consider different levels of organization and how they are connected, a major theme in the PI's introductory biology course, From DNA to Organism. The PI uses the chick auditory system as a model in which to address this question. In particular, the circuit examined underlies the animal's ability to determine the locations of sounds. Neurons connect to each other through their axons, and axons can find their targets due to the integrated functions of proteins called axon guidance molecules. Of the many known axon guidance molecules, the Eph proteins are excellent candidates because previous studies by the PI demonstrate a role for one of these proteins, EphA4, in the accurate formation of connections in the auditory brainstem. Eph proteins are a large family of proteins with complex signaling mechanisms. The proposed research will investigate the role of two other candidate Eph proteins, EphB2 and ephrin-B1, and will examine the interactions between EphA4 and EphB2 during development. The PI has developed methods for introducing genes focally in the auditory brainstem and for tracing axonal connections between regions. These approaches allow for a careful and quantitative determination of which proteins are important for circuit formation, and where they act, and will provide a framework for investigating other classes of molecules.

The educational goal of the PI is a learning-centered approach to teaching biology. The proposed experiments will be performed by students, postdoctoral fellows, and technicians working collaboratively. This hypothesis-based inquiry is also reflected in the coursework taught by the PI. In From DNA to Organism, active learning approaches include group and individual activities to promote observation and information-gathering skills, and comprehension assessment in real-time. In the freshman seminar, discussions of developmental neuroscience are used to demonstrate how scientists obtain information and how skills for scientific inquiry are applied to careers in science. In addition, the PI will organize workshops for faculty and for postdoctoral fellows to provide a forum for developing approaches for active learning and using classroom technology effectively.

Project Report

The two major goals of this project were to perform research to discover mechanisms of nervous system organization and to develop an educational program integrated with this research. The overall goal of the research component of this project was to investigate the development of brain circuitry in the auditory system. This circuitry extracts cues needed to determine the locations of sound sources, and contains connections that form precisely from their initial development. We tested the function of proteins that are known to guide growing axons. The Eph family of proteins is a large family with several members expressed in the developing auditory system. We used gene misexpression and pharmacological approaches to determine how these proteins shape connections. We found that several different family members contribute to distinct aspects of auditory system development in several brain areas involved in hearing. Further studies revealed that these proteins have a role in circuit plasticity that is similar to their role in development. Our results demonstrate that the timing and location of protein expression contributes to the precision in circuit formation. Additionally, the attractive and repulsive effects of Eph proteins on growing axons act in a manner that promotes growth of axons to appropriate target regions. These studies show how multiple factors are integrated to orchestrate neural circuit assembly. The overall goal of the educational component was to provide an integrated, learning-based approach to the study of biological sciences. We enhanced learning in very large, diverse undergraduate biology classes by introducing activities to engage students in problem solving. Additionally, we developed an advanced undergraduate course that focused on developmental neurobiology. Smaller discussion courses complemented these efforts. Undergraduate students were given laboratory training and were incorporated into the research project. Education and outreach through the Minority Science Program increased participation by underrepresented minorities. The project also resulted in contributions to graduate education through training and mentoring in addition to course work. The core course work was enhanced by the addition of a comprehensive unit on nervous system development that included lectures and discussion. These educational goals, together with the integrated research and education plan, resulted in improved effectiveness in teaching biology at several levels, inclusion of a broad population of students, and enhanced mentoring and outreach.

National Science Foundation (NSF)
Division of Integrative Organismal Systems (IOS)
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Program Officer
James O. Deshler
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University of California Irvine
United States
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