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Advancing Real-world Research Among Young Scientists

Research Summary

David Walt develops new array technologies and uses them to collect large amounts of data that can be used to understand fundamental aspects of genetics and cell biology. His HHMI project integrated this experience into undergraduate research, teaching, and outreach efforts and will make scientific research accessible to students who would not normally have the opportunity.

Under the HHMI Professorship, we created the ARRAYS (Advancing Real-world Research Among Young Scientists) project. Undergraduates engaged in research to develop inquiry-based curricula for K-12 students to convey the excitement of working in a multidisciplinary field. Students gained direct knowledge about contemporary research methods as well as the ethical and societal issues surrounding the use of genetic analysis technologies. Undergraduates, graduate students, and postdoctoral associates collaborated to develop outreach materials with a focus on modern chemical biology methods. We developed course materials for conducting all aspects of a modern microarray experiment—a type of experiment that typically requires sophisticated and expensive instrumentation.

Students investigated their maternal ancestry or determined if certain foods (e.g. soybean products) had been genetically modified. We developed simpler materials that could be used in many different learning environments, including undergraduate courses and K-12 classrooms. Students at all levels—graduate students, undergraduate students, and high school students—served as mentors in the project. We give students an appreciation of how modern research is conducted and how science is carried out with teams of workers who collaborate on a common goal. In addition, the project underscored the importance of integrating many scientific and technical fields (chemistry, biology, engineering).

The microarray project is well developed and has been implemented in many different high school classrooms and course materials are available for any class to implement. We are now introducing students to next-gen sequencing as a new technology that enables modern biology research. Students are trained in contemporary methods for analyzing complex biological data and prepared for continued studies and work in bioinformatics. Our Bioinformatics Inquiry through Sequencing (BIOSEQ) research project will use next-generation DNA sequencing to initiate bioinformatics activities and experiments within existing classes at high schools, create an inquiry-based research course at Tufts for advanced high school students, and establish summer professional development workshops for teachers in bioinformatics. Additionally, we will support teachers in their classroom activities with undergraduate science mentors who will visit the classrooms during bioinformatics activities, assist the teacher, and serve as role models for high school students. BIOSEQ will provide science teachers with support to successfully adopt the new focus on inquiry and an excellent platform to introduce students to the process of science by proposing questions and using interdisciplinary strategies to answer them. 

This past year, a sequencing center was established for educational use at Tufts University’s Medford Campus. The center is comprised of a next-generation DNA sequencer capable of sequencing microbial-sized genomes and targeted sequencing and has equipment, reagents, and knowledgeable people to assist educators and students in developing and completing experiments. This sequencing center will be available to college students and high school students through college-level research courses, and will also be available to educators and students who wish to integrate sequencing into classroom projects, science fair projects, and college-level theses.

Currently, the BIOSEQ research team is developing three modules that can be integrated into existing high school biology classes. The first module would allow students to generate a “portrait” of their microbiome by sequencing specific regions of the 16S rDNA of bacteria captured by swabbing the body at different sites. The second module addresses “the genetics of race” by sequencing students’ mitochondrial DNA and discussing the relative similarity between classmates. The third module studies mutations by sequencing a plasmid that was transformed into a DNA-repair-deficient strain of E. coli.  This spring, we will pilot test one or more of these modules in one or more of our partner high schools.

Research in the Walt Lab

The Walt group's research effort employs optical microwell arrays for the detection and analysis of single molecules. In one area, fundamental enzymology is investigated by observing a population of single enzyme molecules. Individual enzyme molecules are enclosed with fluorogenic substrate in a high-density microwell array. The substrate turnover in the microchambers can be monitored with fluorescence microscopy. The large array size provides excellent statistics. These experiments provide mechanistic insight into a variety of enzymes including RNase, horseradish peroxidase, beta-galactosidase, and restriction endonucleases. Mechanisms of inhibition can be determined and conformational changes leading to changes in enzyme activity can be monitored.

In addition to these fundamental studies, the single molecule array technology has been used for ultra-high sensitivity DNA and protein detection. We are using this ultra-high sensitivity to develop diagnostic tests for early detection of breast cancer and infectious diseases. In another project, the lab is investigating the use of integrated microfluidic systems combined with microwell arrays to study populations of individual cells, and analyze the contents of these cells with single molecule detection. These isolated cells and molecules exhibit properties that are very different from their ensemble mean. This work is leading to a better understanding of the behavior of collections of molecules and populations of cells.

Last updated May 2014

Scientist Profile

David Walt
HHMI Professor
Harvard Medical School
Chemical Biology