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A Program for Teaching Introductory-Level Biology
Summary: Richard Losick's research interests include RNA polymerase, gene transcription and its control, and development in microorganisms. His HHMI project uses interdisciplinary and active-learning approaches to improve the pedagogy for teaching introductory molecular biology. The project also provides long-term research experiences for students from economically or educationally disadvantaged backgrounds, and it is building a community of science-dedicated students who can support and mentor each other during their undergraduate years and beyond.
HHMI PROJECT SUMMARY
Original Project (2002 grant)
The initial grant supported the development of a three-part project involving undergraduate education in the biological sciences at the introductory level. The first part, FEEDS (Freshmen from Economically or Educationally Disadvantaged Backgrounds in Science), is aimed at students who enter Harvard with a strong interest in science but whose school or home location and situation has not allowed them to pursue advanced courses or research opportunities. Each year since 2002, up to six freshmen have been paired with science faculty to take on a multiyear, inquiry-based research project. Students from disadvantaged backgrounds are at risk for dropping out of science, so the idea is that an open-ended research experience and a long-standing relationship with a faculty mentor will keep students excited about science for the remainder of their undergraduate careers and beyond. The FEEDS students, who are on scholarship, receive stipends for doing their research (during the term and summer) in lieu of having to contribute to meeting their educational expenses by pursuing other kinds of work. FEEDS also creates a community of students who, in turn, mentor other science-dedicated students from disadvantaged backgrounds.
The second part of the project involved enhancements for teaching concepts and lab procedures in my sophomore-level introductory course on molecular biology, Biological Sciences 52. Working with a professional animator, I developed Web-based animations on topics such as the DNA replication fork and protein biosynthesis. A new bioinformatics module, developed in conjunction with a colleague in the Department of Statistics, includes a student-friendly, Web-based version of an algorithm called BioProspector, which identifies sequence logos for regulatory proteins based on transcriptional profiling data. Students presented with data from a gene microarray experiment are able to use BioProspector to identify the recognition sequence for the regulatory protein in question. Instead of the standard laboratory module, students in the course who have extensive prior lab experience are able to take on a semester-long research project under the supervision of a postdoctoral fellow.
The third part of the project, the Undergraduate Experimental Biology Program (MCB100), was created to give students a chance to experience how science is done through the practice of experimental inquiry and to forge ties between Harvard research faculty and undergraduates. Students are divided into small teams, each team assigned to a different project tied to ongoing research in the labs of participating faculty members. The projects, which are diverse, have included studying the genetic regulation of Bacillus subtilis biofilm formation, using systemic RNAi to study C. elegans, and constructing and screening a cosmid-based environmental DNA (eDNA) library to identify novel natural products produced by uncultured bacteria. Unlike students in a standard laboratory course, students in MCB100 carry out research projects for which the outcomes are unknown. At the end of the term, students make oral presentations on their research and prepare reports modeled on the NIH R01 grant format. The program has been institutionalized at Harvard College and is now a self-sustaining part of the curriculum.
Project Update (2006 grant)
The FEEDS program will be maintained with a steady state participation of up to 25 students in their sophomore, junior, and senior years. The community-building aspect of FEEDS will be expanded by introducing a range of additional activities designed to reinforce students' sense of accomplishment and provide support for students joining the program. Activities will include off-campus retreats for current FEEDS students and, periodically, for FEEDS alumni. I will also create a Web site where students can contact and obtain advice and network with FEEDS alumni.
A second project involves making Biological Sciences 52 more interdisciplinary and quantitative by using more active-learning approaches and widening the subject matter to include the physical chemistry of macromolecules. Working with a professional animator I will create interdisciplinary animations in molecular biology that integrate concepts from chemistry, biology, and physics. I will also develop modules that incorporate approaches from other disciplines such as statistics and physics. To foster an active-learning experience I will prepare interactive lectures that take advantage of personal response devices technology and develop a Web-based series of interactive problem sets in biophysics.
RESEARCH SUMMARY
My research interests include RNA polymerase, gene transcription and its control, and development in microorganisms. I study a class of transcriptional regulatory proteins called sigma factors that bind to the RNA polymerase in bacteria and confer on it the capacity to recognize sequences called promoters, sites in the DNA from which genes are transcribed. Each sigma factor confers on RNA polymerase the ability to transcribe a distinct set of genes from a distinct set of promoters.
I have a special interest in the developmental process of spore formation in the soil bacterium B. subtilis. Sporulation is governed by a cascade of five developmental sigma factors that appear in a temporally and spatially ordered sequence over the course of development. A hallmark of sporulation is the formation of an asymmetrically positioned division septum that divides the developing cell into dissimilar-sized progeny cells that express different sets of genes under the control of cell-specific sigma factors. Among the questions that are being addressed are how cells divide asymmetrically, how asymmetric division gives rise to differential gene expression, how the progeny cells communicate with each other, and how gene expression is coupled to landmark events in morphogenesis. Underlying the answers to these questions are proteins that localize to particular sites in the cell, often in a highly dynamic manner. An important challenge is understanding how proteins determine their proper subcellular address and how their function is tied to their location.
I am also interested in morphogenesis in the filamentous bacterium Streptomyces coelicolor. This unusual bacterium grows by forming a branching network of hyphae (filamentous cells) known as the substrate mycelium. This substrate mycelium gives rise to an aerial mycelium consisting of hyphae that grow into the air away from the colony surface and metamorphose into chains of pigmented spores. Formation of the aerial mycelium appears to involve extensive intercellular signaling. I am studying genes involved in this developmental process and attempting to elucidate the intercellular signal transduction pathways that govern development.
Another topic of interest is the problem of chromosome segregation in bacteria. Bacteria lack a conspicuous mitotic apparatus and yet are able to segregate daughter chromosomes with high fidelity. The visualization of specific sites on the chromosome in living cells has revealed that replication origin regions rapidly move toward opposite poles of the cell but the nature of the motor that drives origin regions apart is not known.
Last updated March 2007
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