Bioinformatics at Carleton
"Research, development, or application of computational tools and approaches for expanding the use of biological, medical, behavioral or health data, including those to acquire, store, organize, archive, analyze, or visualize such data".
(definition from The National Institutes of Health)
The interdisciplinary field of Bioinformatics is used to answer biological questions by combining computational, software, and database tools. At Carleton, bioinformatics tools are integrated into and across our Biology curriculum. Some of the newest additions to Biology courses below illustrate this embedded approach.
DNA Microarray Lab in a Molecular Biology Course
Prof. Stephan Zweifel is developing a laboratory "case study" in his Molecular Biology course using DNA microarrays to detect genome-wide expression patterns in yeast cells in response to mitochondrial DNA mutations. The exercise is intended to engage students in bioinformatics inquiry: blending genetics and computational biology. In addition to introducing students to a current genomics technique, this is an example of what one can accomplish with the wealth of DNA sequence information currently available. The hope is that students who have this laboratory experience will shed preconceived notions about the compartmentalization of the cell, and start viewing the cell as an interconnected network of gene regulatory pathways.
Until recently, geneticists have been limited to studying the genome of an organism "one gene at a time" through mutational analysis. But with the accumulation of vast amounts of DNA sequence information in the last ten years, molecular geneticists have expanded their studies of gene function to the cell-wide level. This global approach to studying gene expression and gene interaction is called functional genomics.
In one application of this technology, total RNA is extracted from a culture of cells (this population of RNA thus represents all the genes that are "turned on"). The RNA is fluorescently labeled, and then hybridized with the microarray. The fluorescent RNA molecules will bind to spots of DNA on the microarray that are complementary, and are detected by a laser beam illuminated microscope. In the common "two-color assay", fluorescently labeled samples prepared from RNA of two different cell populations are co-hybridized onto the microarray to measure relative gene expression levels. This technique provides a unique genome-wide profile of gene expression.
In this lab, students will begin by isolating total RNA from cells with defined mtDNA mutations. The RNA will then be labeled with a fluorescent dye, and then hybridized to a microarray slide. The laser scanning of the slide will be done off-site. The turn-around time for the raw data however is rapid, and students will have plenty of time to wade through a very large bioinformatics data set. The yeast genome database is one of the best organized, and annotated sites available to the public. In other words, students should encounter a "user friendly" genomics environment.
New Comparative Genomics Lab Project in a Plant Development Course
Prof. Susan Singer developed a term-long lab project for her Plant Development course that involves comparative genomics. This lab was offered in spring 2005. Students cloned homologs of Medicago truncatula and Pisum sativum inflorescence architecture genes from the native prairie plant Chamaecrista fasiculata. All three plants are legumes, but C. fasiculata is a basal legume with a different inflorescence architecture. Students used bioinformatics tools to design primers for PCR-based cloning and for comparison of their sequences with known sequences in legumes and other families. The goal is to uncover small sequence changes that could correlate with different architectural plans. Phylogenetic trees based on sequence were compared with community consensus trees. In the next offering of this course, students will pick up the project and continue sequencing and comparing these key floral regulatory genes.
New Bioinformatics Components in Introductory Biology Labs
Three separate versions of our Introductory Biology 125 course (Genes, Evolution, and Development) now have two labs with strong bioinformatics components that use a range of tools in Student Biology Workbench. At the beginning of the term, students spend two weeks using both morphological and molecular traits to build primate phylogenies. The lab effectively addresses diversity and evolution. At the end of the term, when students have substantially more sophistication in development and molecular genetics, they engage in a lab that looks at the evolution and development of cauliflower and broccoli. Students use sequence databases and bioinformatics tools to identify a premature stop codon in a flowering gene in broccoli and cauliflower, and then trace the phylogenetic origins of this mutation.
Other Information about Bioinformatics