This study stems from our conviction that undergraduate science education should closely follow recent advances in scientific research. Textbooks and pre-planned laboratory experiments are important components of undergraduate training. However, we believe firsthand experience of the entire scientific discovery process is crucial for preparing the student for a productive career in modern biological and biomedical sciences.
The complete sequencing of several eukaryotic genomes has now made it possible to create experiments in functional genomics for the undergraduate student. Here, we show an innovative approach to incorporate professional functional genomics research into the biology education of 138 undergraduate students over a period of two years. We have demonstrated that if carefully planned and carried out, a significant number of undergraduates can not only benefit from their own discovery-based learning processes, but also collectively produce a large amount of high-quality data that have a meaningful scientific impact for the research community.
In each 10-week academic quarter, 24-28 undergraduates from different departments (the majority of them 1st and 2nd year students) were enrolled in a lower-division class named Life Sciences 10 Honors (LS10H). The class consists of a research laboratory, a computer laboratory, and a series of lectures. Students in LS10H characterized 1375 lethal mutations and identified 499 eye phenotypes (see research methods). Each quarter, approximately 5 students who complete LS10H were selected to participate in an advanced series of three upper-division classes, called Life Sciences 100 Honors (LS100H) A/B/C. In addition to working on individual projects, these advanced students also verified the data of the LS10H students.
To enable the student's success, the lecture series is closely coordinated with the student's research program (see sample syllabus). The only prerequisite for LS10H is AP level Biology in High School. Therefore, care is taken to avoid jargon. All students are familiar with the general concepts of the central dogma of molecular biology, basic Mendelian genetics and segregation properties of chromosomes during mitosis and meiosis. This is all that is really needed for initiating the lecture series. The concepts are largely developed ab initio as logical genetic paradigms. Basic concepts of genetics and genomics are emphasized to establish that studies using model systems can create the foundation for medical research. Most of the students involved are medical school bound, and we make no attempt to change their minds on their career choice. However, we do emphasize that they have several career options to choose from. Towards the middle of the quarter, specific information pertaining to the experiments is provided. By the end of the quarter, however, we return to basics, this time emphasizing how modern developments in genomics can revolutionize the biomedical sciences. Some training in research ethics and expert lectures on research are also part of the curriculum. The midterm is an NIH style grant proposal (see the sample midterm--which was written by a student). The final paper is written as a manuscript for a journal (see the sample final--which was written by a student). There are no textbooks used for the class. The lecturing style is rather freeform and interactive. Lectures are delivered both in a classroom setting and inside the laboratory. Students are assessed for grades based on a large number of criteria (see sample syllabus). Students evaluate the instructors and course on a standard UCLA evaluation form. The ultimate goal of the didactic component is to emphasize "learning through hearing" as in a scientific seminar setting and developing in the student the ability to create links between ideas and to correlate a wide spectrum of concepts.
There are 5-6 computer sessions in LS10H each quarter. The first two sessions involve the use of a web-based virtual Fly Lab (http://biologylab.awlonline.com), in which students are reinforced on basic Mendelian concepts taught in the lectures. After a short demonstration of how to use the software, the class is divided into groups of two and three (at each computer) so that within a group there is extensive discussion and interaction, that is essential for solving the assigned genetic problems. These computer exercises supplement the laboratory instruction by allowing the students to perform virtual crosses and obtain the progeny phenotypes and ratios in seconds, whereas a one generation cross normally takes about two weeks in a real laboratory. During the next 3-4 sessions, students learn how to obtain necessary information on their assigned mutations and fly stocks from FlyBase (http://www.flybase.net), the largest Drosophila genomic database, and NCBI database ( http://www.ncbi.nlm.nih.gov). They perform BLAST searches in FlyBase to determine the exact insertion site of the P-element and the gene that is likely to be disrupted. Once they obtain the sequences of their genes, protein-protein BLAST searches are carried out in the NCBI database to look for significant homology to well-defined domains in the proteins. These exercises enhance the understanding of their own research projects as they learn the likely function of their assigned genes and begin to appreciate the powerful tools of bioinformatics.
There are two laboratory sections, each can accommodate up to 15 students. A typical LS10H student spends an average 18-20 hours each week on these projects. Assistance from an instructor was made available full-time in the laboratory to facilitate continuous guidance. LS100H students also provide significant mentoring to the LS10H students. During the first week of the laboratory, students set up their first crosses and learn basic Drosophila genetic techniques, including sexing males and females, collecting virgins to set up crosses, adult genetic markers, and basic microscopy. As their projects progress, they begin to learn more complex genetic concepts based on their new crosses (Figure S1 in research methods). For example, in the F1 cross they become familiar with P-element transposition and its use as a mutagenesis tool, as well as the concept of balancer chromosomes that eliminate progeny resulting from meiotic recombination. In F2 crosses, they learn the usefulness of using natural meiotic recombination to genetically engineer flies and to map mutations with respect to genetic markers. Specifically, they calculate the recombination distance between each unique P-element induced mutation and the FRT site (a fixed marker). The most important and difficult central concept, inducing FLP-mediated mitotic recombination, is introduced by the time of the F3 cross (Figure S2 in research methods). From their high school AP biology classes, students are familiar with "mitosis" and "recombination" but have always known that the two never mix, as recombination is a meiotic phenomenon. For all students, the fact that their core experiments involve "mitotic recombination" is a study in "out of the box" thinking. Students also learn the difference between the artificially induced mitotic recombination that occurs in the somatic cells of F3 progeny and natural meiotic recombination, which takes place in the female germline. By the time of the F4 generation, most students will have gained an appreciation for using mitotic recombination to bypass the lethality caused by homozygosity of their assigned lethal mutations. Mosaic clones allow for the analysis of recessive lethal genes on eye development. Students then document interesting eye phenotypes in these following categories: rough, cell lethal and glossy. In this project, 501 total phenotypes were classified in these categories. The retrospectively determined rate (36%) for finding phenotypes ensured that every student isolated at least one eye mutant, providing every student with the exhilaration of discovery, thus enhancing their learning experience.