Module 2: Expression EngineeringModule 2: Expression Engineering20.109Lecture 7November 1st, 2007Cite as: Natalie Kuldell. Course materials for 20.109 Laboratory Fundamentals in Biological Engineering, Fall 2007. MITOpenCourseWare (http://ocw.mit.edu), MassachusettsInstitute of Technology. Downloaded on [DD Month YYYY].Sparks of inspirationJudah Folkman1950s Surgical Resident MGH “the warmth of tumors made him wonder whether they, like the other tissue in the body, needed their own blood supply and whether they could be starved if that blood supply was cut off”Photo courtesy of Noll Steinweg.Figure by MIT OpenCourseWare.Photo courtesy of Children's Hospital Boston.Used with permission.Cite as: Natalie Kuldell. Course materials for 20.109 Laboratory Fundamentals in Biological Engineering, Fall 2007. MITOpenCourseWare (http://ocw.mit.edu), MassachusettsInstitute of Technology. Downloaded on [DD Month YYYY].Sparks of inspirationexisting blood supply enoughno such molecules known tumors red from inflammationFigure by MIT OpenCourseWare..Photo courtesy of Children's Hospital Boston.Used with permission.Cite as: Natalie Kuldell. Course materials for 20.109 Laboratory Fundamentals in Biological Engineering, Fall 2007. MITOpenCourseWare (http://ocw.mit.edu), MassachusettsInstitute of Technology. Downloaded on [DD Month YYYY].Sparks of inspirationhttp://www.childrenshospital.org/research/videos/3_Isolating.movrabbit corneatumor + polymer + inhibitor -inhibitorThree photos removed due to copyright restrictions.Photo courtesy of Children's Hospital Boston.Used with permission.Cite as: Natalie Kuldell. Course materials for 20.109 Laboratory Fundamentals in Biological Engineering, Fall 2007. MITOpenCourseWare (http://ocw.mit.edu), MassachusettsInstitute of Technology. Downloaded on [DD Month YYYY].Sparks of inspirationClinical translation2004 FDA approval for endostatinImage courtesy of Children's Hospital Boston.Used with permission.Photo courtesy of Children's Hospital Boston.Used with permission.Cite as: Natalie Kuldell. Course materials for 20.109 Laboratory Fundamentals in Biological Engineering, Fall 2007. MITOpenCourseWare (http://ocw.mit.edu), MassachusettsInstitute of Technology. Downloaded on [DD Month YYYY].Sparks of inspirationClinical translationhttp://www.affymetrix.com/community/wayahead/macular_degeneration.affx2004 FDA approval for endostatin2007 10 anti-angiogenesis treatments approved32 countriescancer + macular degenerationCourtesy of Affymetrix. Used with permission.Image courtesy of Children's Hospital Boston.Used with permission.Photo courtesy of Children's Hospital Boston.Used with permission.Cite as: Natalie Kuldell. Course materials for 20.109 Laboratory Fundamentals in Biological Engineering, Fall 2007. MITOpenCourseWare (http://ocw.mit.edu), MassachusettsInstitute of Technology. Downloaded on [DD Month YYYY].AMD: Age-related Macular Degeneration15 million people in the US suffer from AMD# is expected to double as baby boomers age50 unaffected96 patients100K SNP array (Affymetrix)Genome-wide genotype analysisCourtesy of Affymetrix. Used with permission.Cite as: Natalie Kuldell. Course materials for 20.109 Laboratory Fundamentals in Biological Engineering, Fall 2007. MITOpenCourseWare (http://ocw.mit.edu), MassachusettsInstitute of Technology. Downloaded on [DD Month YYYY].Science (2005) 308:385Both SNPs in gene for Complement Factor HSNP encodes Y402H mutationScience (2005) 308:419Science (2005) 308:421Genome-wide genotype analysisFigure removed due to copyright restrictions. Figure 1 in Klein, R., et al. “Complement Factor H Polymorphism in Age-Related Macular Degeneration.” Science 308 (2005): 385.Cite as: Natalie Kuldell. Course materials for 20.109 Laboratory Fundamentals in Biological Engineering, Fall 2007. MITOpenCourseWare (http://ocw.mit.edu), MassachusettsInstitute of Technology. Downloaded on [DD Month YYYY].YY= homozygous for Y402 HH = homozygous for Y402H SNPWesternC-reactive protein (CRP) Complement Factor H (CFH)Genome-wide genotype analysisCourtesy of National Academy of Sciences, U.S.A. Used with permission.Source: Johnson, P. T., et al. "Individuals Homozygous for the Age-RelatedMacular Degeneration Risk-Conferring Variant of Complement Factor H HaveElevated Levels of CRP in the Choroid." PNAS 103 (2006): 17456. DOI: 10.1073/pnas.0606234103 . Copyright (c) 2006 National Academy of Sciences, U.S.A.Cite as: Natalie Kuldell. Course materials for 20.109 Laboratory Fundamentals in Biological Engineering, Fall 2007. MITOpenCourseWare (http://ocw.mit.edu), MassachusettsInstitute of Technology. Downloaded on [DD Month YYYY].Watercolor illustration by Thomas Hunt Morgan, 1919. Genome-wide phenotype analysisArrays for RNAi drug discoveryFeatures: $$$automatedcollaborative grow at RTambient CO2no lipid needed for txn“The researchers involved in the three-year, $18 million initiative successfully built a library of 160,000 custom-designed RNAi constructs targeting 15,000 human genes and 15,000 mouse genes. They also developed methods to apply this library effectively for loss-of-function genetic screens. This fundamental resource is available to scientists worldwide through Sigma-Aldrich and Open Biosystems.”Souce: http://www.broad.mit.edu/genome_bio/trc/ [Accessed June 12, 2008]Courtesy of the Broad Institute. Used with permission.Cite as: Natalie Kuldell. Course materials for 20.109 Laboratory Fundamentals in Biological Engineering, Fall 2007. MITOpenCourseWare (http://ocw.mit.edu), MassachusettsInstitute of Technology. Downloaded on [DD Month YYYY].Nature Reviews Genetics 2006 7: 373Genome-wide phenotype analysisOne possible screening paradigmdrug has no effect on cellsCourtesy of Norbert Perrimon. Used with permission.Cite as: Natalie Kuldell. Course materials for 20.109 Laboratory Fundamentals in Biological Engineering, Fall 2007. MITOpenCourseWare (http://ocw.mit.edu), MassachusettsInstitute of Technology. Downloaded on [DD Month YYYY].Nature Reviews Genetics 2006 7: 373Genome-wide phenotype analysisOne possible screening paradigmscreen to find siRNAs with some effect on cellsCourtesy of Norbert Perrimon. Used with permission.Cite as: Natalie Kuldell. Course materials for 20.109 Laboratory Fundamentals in Biological Engineering, Fall 2007. MITOpenCourseWare (http://ocw.mit.edu), MassachusettsInstitute of Technology. Downloaded on [DD Month YYYY].Nature Reviews Genetics 2006 7: 373Genome-wide phenotype analysisOne possible screening