Module 2 Expression Engineering 20 109 Lecture 7 November 1st 2007 Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY Sparks of inspiration Judah Folkman 1950s Surgical Resident MGH Photo courtesy of Noll Steinweg Photo courtesy of Children s Hospital Boston Used with permission 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 Figure by MIT OpenCourseWare Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY Sparks of inspiration existing blood supply enough no such molecules known Photo courtesy of Children s Hospital Boston Used with permission tumors red from inflammation Figure by MIT OpenCourseWare Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY Sparks of inspiration Photo courtesy of Children s Hospital Boston Used with permission rabbit cornea Three photos removed due to copyright restrictions tumor polymer inhibitor inhibitor http www childrenshospital org research videos 3 Isolating mov Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY Sparks of inspiration Clinical translation 2004 Image courtesy of Children s Hospital Boston Used with permission Photo courtesy of Children s Hospital Boston Used with permission FDA approval for endostatin Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY Sparks of inspiration Clinical translation Image courtesy of Children s Hospital Boston Used with permission 2004 Photo courtesy of Children s Hospital Boston Used with permission FDA approval for endostatin 2007 10 anti angiogenesis treatments approved 32 countries cancer macular degeneration http www affymetrix com community wayahe ad macular degeneration affx Courtesy of Affymetrix Used with permission Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY Genome wide genotype analysis AMD Age related Macular Degeneration 15 million people in the US suffer from AMD is expected to double as baby boomers age 50 unaffected 96 patients 100K SNP array Affymetrix Courtesy of Affymetrix Used with permission Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY Genome wide genotype analysis Both SNPs in gene for Complement Factor H Figure 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 SNP encodes Y402H mutation Science 2005 308 419 Science 2005 308 421 Science 2005 308 385 Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY Genome wide genotype analysis Western C reactive protein CRP Complement Factor H CFH Courtesy of National Academy of Sciences U S A Used with permission Source Johnson P T et al Individuals Homozygous for the Age Related Macular Degeneration Risk Conferring Variant of Complement Factor H Have Elevated 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 YY homozygous for Y402 HH homozygous for Y402H SNP Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY Genome wide phenotype analysis Arrays for RNAi drug discovery 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 Watercolor illustration by Thomas Hunt Morgan 1919 grow at RT ambient CO2 no lipid needed for txn Features automated collaborative Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY Genome wide phenotype analysis One possible screening paradigm Courtesy of Norbert Perrimon Used with permission drug has no effect on cells Nature Reviews Genetics 2006 7 373 Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY Genome wide phenotype analysis One possible screening paradigm Courtesy of Norbert Perrimon Used with permission screen to find siRNAs with some effect on cells Nature Reviews Genetics 2006 7 373 Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY Genome wide phenotype analysis One possible screening paradigm Courtesy of Norbert Perrimon Used with permission screen to find siRNAs with some effect on cells Nature Reviews Genetics 2006 7 373 Cite as Natalie Kuldell Course materials for 20 109 Laboratory Fundamentals in Biological