This course provides an introduction to the properties of, and technologies for detecting, biological molecules such as proteins and nucleic acids, including methods and uses for DNA sequencing. As such, it provides an introduction to molecular-level biology for students with physical science/engineering backgrounds. The course evolved from courses given to upper class undergraduates and first year graduate students at George Washington University, most of whom were bioengineering, electrical or mechanical engineering majors. The course focuses on nanoscale phenomena involving biological macromolecules. Much of the course is based on careful reading of seminal journal articles, and thus it also teaches how to critically analyze technical/scientific literature. Course materials include 11 videotaped lectures, 12 powerpoints, 3 homework problem sets and a midterm exam. The papers that are reviewed form a critical part of the course and are available online from most academic libraries (see references).
Topics by class:
Class 1 Molecules that biosensors sense and molecules used for specificity
Class 2 Enzyme linked "sandwich" immunoassays, label-free surface plasmon resonance sensors
Class 3 Mass transport: binding kinetics, flow, diffusion; immunochromatography and pcr
Class 4 Single-molecule ELISA based on femtoliter confinement
Class 5 Microcantilever mechanical sensor
Class 6 Single-molecule fluorescence, TIRF, FRET
Class 7 FET, WGM and GMR as signal transducers
Class 8 DNA mechanics and nanoscale engineering with DNA
Class 9 DNA engineering including pcr and molecular evolution
Class 10 DNA sequencing: Sanger method; emulsion pcr, bead capture and FET array biochemistry
Class 11 DNA sequencing: Illumina method – surface pcr and removable fluorescent labels
Class 12 Applications of DNA sequencing in cancer treatment
The instructor was a principal investigator at NIH with a background in physics, molecular biology and medicine. The course was developed as part of an NSF grant for undergraduate education in Nanotechnology.
Class 1. Philip Nelson, Biological Physics. Ch. 1, 2. Class 2. Philip Nelson, Biological Physics, Ch. 4. Class 3. L. Chang et al., Single molecule enzyme-linked immunosorbent assays: theoretical considerations. Journal of Immunological Methods 378:102-115 (2012) Class 4. T. M. Squires et al., Making it stick: convection, reaction and diffusion in surface-based biosensors. Nature Biotechnology 26:417-426 (2008). Class 5. T. P. Burg et al., Weighing of biomolecules, single cells and single nanoparticles in fluid. Nature 446:1066-1069 (2007). Class 6. A. Jain et al., Probing cellular protein complexes using single-molecule pull-down. Nature 474: 484-489 (2012). Class 7. F. Patolsky et al., Electrical detection of single viruses. Proc. Natl. Acad. Sci. 101:14017-14022 (2004); A. M. Armani et al., Label-free single molecule detection with optical microcavities. Science 317:783-787 (2007); R. S. Gaster et al., Matrix-insensitive protein assays push the limits of biosensors in medicine. Nature Medicine 15: 1327-1331 (2009). Class 8. 2d-DNA tile arrays-He et al., Journal of the American Chemical Society 127:12202 (2005); 3-d polyhedral: He et al. Nature 452:198 (2008); DNA tubes: Yin et al., Science 321:824 (2008). Class 9. C. Bustamante et al., Ten years of tension: single-molecule DNA mechanics. Nature 421:423-427 (2003). Class 10. J. M. Rothberg et al., An integrated semiconductor device enabling non-optical genome sequencing. Nature 475:348-352 (2011). Class 11. Illumina, Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456:53-59 (2008). Class 12. L. A. Diaz Jr. et al., The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486:537-540 (2012).
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