Integrative activities to study the evolution of nervous system function part of Teaching Genomics at Small Colleges:Genomics Instructional Units Minicollection
The next generation of neurobiologist needs to be ready to put gene sequences into a functional context at the level of cells, neural systems, and ultimately behavior of the organism. Comparative genomics offers a powerful opportunity to engage neurobiology students in integrative thinking because it necessarily involves considering nervous system functions in the broadest evolutionary context, and raises questions that lend themselves naturally to multiple levels of analysis. This multi-week series of laboratory exercises gives students a chance to become familiar with, and apply genomics analysis tools to explore the hypothesis that specialized nervous system functions will have a "genomic signature." Week 1: Learn to use basic genomics tools to address a question relevant to neurobiology. Students begin the first session familiar with the ionic basis of the action potential such that they are ready to deconstruct a variety of action potential phenotypes into expression of subtypes of ion channels. A computer-based exercise introduces them to basic genomic tools (BLAST & Genbank searches) and provides data insight into the relative evolutionary conservation of sodium and potassium channels. Week 2: Game of Integration. Building on the concept that electrical excitability of neurons is conferred by specific gene products localized to specific intracellular locations, the second week examines the integral role of glial-neuronal interactions in nervous system signaling in the mammalian brain. This is intended as an open-ended exercise, but we designed a "game of integration" modeled after a grant proposal to scaffold student inquiry. Students work in groups to brainstorm about candidate gene products they would expect to be clustered in association with myelination or the tripartite synapse, building on background information from class and journal club. An emerging literature is enhancing resources for investigating neuron-glia interactions and illuminate new questions about the phylogenetic distribution of glia in nervous systems (e.g. apparent convergent evolution of myelin in invertebrates). Weeks 3 and 4: Comparative Evolution Project and Poster Session. Students now use their candidate genes identified in Week 2 as a probe for studying the evolution of a neuron-glial relationship by performing comparative genomic analyses. During the poster session, teams present their project findings to the class and invited "external reviewers" consisting of professors with expertise in genetics/molecular biology, evolutionary biology, and comparative anatomy. This exposes students to scientific debate as they, we, and our departmental colleagues interpret data from multiple perspectives. Groups collaborate to make informal posters to present both the mouse-based integrative analysis and the comparative genomic analyses. Faculty colleagues with expertise in molecular biology, evolutionary biology and comparative physiology are invited to the session to emphasize that the students are engaged in real science. This exercise is intended to develop iteratively across multiple classes, like a grant would across multiple renewals. Making examples of the work of the last class improves scaffolding, sharpens thinking and allows the next class to dig deeper into the key questions. It is also becoming easier to teach integration from genome to behavior and from cnidarians to humans as models of this kind of analysis begin to appear in the literature. While this exercise is framed in terms of comparative "neuro-gliomics," it can be readily adapted to explore the genomic signature of comparative evolution of a variety of neural processes (e.g., FOXP2 and language, NMDA receptor and experience-dependent plasticity or PAR proteins and neuron polarity) appropriate to the instructor's expertise and research interests.