MIT20_020S09_prj17_onco_fnp

MIT20_020S09_prj17_onco_fnp - Final Presentation Final...

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Unformatted text preview: Final Presentation Final Anonymous student MK and NM Image credits: Left, courtesy of Torsten Witmann, used with permission. Right, Donald Bliss and Sriram Subramaniam, National Library of Medicine, NIH. OUR MISSION OUR CANCER METASTASIS COMMON DISEASE, KILLS 500,000 A YEAR ABNORMAL CELL GROWTH AND DIVISION ABNORMAL CAN ORIGINATE IN DIFFERENT ORGANS SPREAD FROM ORIGINAL TUMOR TRAVELS THROUGH BLOOD/LYMPH MAIN CAUSE OF DEATH OUR MISSION OUR A SOLUTION IMPACT DIAGNOSTIC IMAGING TOOLS BETTER UNDERSTANDING OF METASTASIS PATTERNS OF MOVEMENT, TIMING LEAD TO DEVELOPMENTS IN TREATMENTS COULD BE USED FOR KILLING CANCER CELLS SCIENCE BEHIND IT SCIENCE SIGNALS OVEREXPRESSION OF ENZYMES COX-2: PREVENTS APOPTOSIS MMP-1: BREAKS BASEMENT MEMBRANE Image: http://www.rcsb.org/ Courtesy of Larry Marnett, Ph.D. Used with permission. http://www.mc.vanderbilt.edu/lens/article/?id=49&pg=999 SCIENCE BEHIND IT SCIENCE DETECTION RIBOZYMES CLEAVE MRNA PRODUCTS OF REACTIONS BINDING ENDS LUCIFERASE INHIBITION EXPRESSION LEADS TO LIGHT Image removed due copyright restrictions. Fluorescent imaged mouse, from http://www.caliperls.com/tech/ optical-imaging/image-gallery/oncology-angiogenesis-models.htm HOW IT WORKS HOW TREATMENT REMOVE PATIENT CELLS ADD PLASMIDS/CHANGE DNA DELIVER MODIFIED T-CELLS ADD DOSE OF LUCIFERIN TAKE IMAGES WITH CCD CAMERA Image removed due copyright restrictions. Photo of CCD imaging system, http://www.caliperls.com/ products/contract-research/in-vivo/optical-imaging-studies.htm HOW IT WORKS HOW SYSTEM OVERVIEW ENDOCYTOSIS EXPRESSION EXPRESSION BINDING DIFFUSION LIGHT HOW IT WORKS HOW TIMING DIAGRAM COLLAGEN RECEPTOR S A “DEBRIS” PROSTANOIDS INHIBITOR LIGHT PRODUCER S A S A HOW IT WORKS HOW DEVICE OVERVIEW COLLAGEN RECEPTOR RECEPTOR INHIBITOR LIGHT PRODUCER BREAKING IT DOWN BREAKING COLLAGEN RECEPTOR COLLAGEN BINDS ENDO180 ENDOCYTOSIS OF COLLAGEN COLLAGEN BREAKING IT DOWN BREAKING COLLAGEN RECEPTOR PARTS STRONG PROMOTER ENDO180 RECEPTOR GENE GFP FOR TESTING/DEBUG MCMV ENDO180 GFP BREAKING IT DOWN BREAKING INHIBITOR RIBOZYME CLEAVAGE OF MRNA INHIBITION ENDS BREAKING IT DOWN BREAKING INHIBITOR PARTS PROMOTER DEPENDENT ON LUCIFERASE RIBOZYME GENE DOUBLE APTAMER LOOP RIBOZYME APTAMERS BREAKING IT DOWN BREAKING LIGHT PRODUCER LIGHT LUCIFERASE LUCIFERIN O2 OXIDIZES PIGMENT PIGMENT BREAKING IT DOWN BREAKING LIGHT PRODUCER PARTS STRONGEST PROMOTER, COULD VARY LUCIFERASE GENE GFP FOR TESTING/DEBUG H2CMV SV40 LUCIFERASE GFP PUTTING IT TOGETHER PUTTING REVIEW OF SYSTEM LIGHT POTENTIAL PROBLEMS POTENTIAL UNKNOWNS CHANGES DEGREE OF VISIBILITY COLLAGEN DEGRADATION IMMUNE RESPONSE DIFFERENT RECEPTORS LONGER DETECTION TIME OTHER SIGNAL BESIDES LIGHT MAKING IT WORK MAKING TESTING PROMOTER STRENGTH IN-VITRO BINDING TO RIBOZYME ENDOCYTOSIS EXPERIMENTS EXPRESSION OF RECEPTOR/LUCIFERASE DEBUGGING PRESENCE OF LUCIFERIN LUCIFERASE REACTIONS USE OF GFP IN VITRO FREEZE-FRACTURE METHOD Image removed due copyright restrictions. D-Luciferin Firefly vial from Caliper Life Sciences (http://www.caliperls.com) MAKING IT WORK MAKING A PLAN RECEPTOR EVOLUTION FOR SPECIFICITY SLOW DEGRADATION APTAMER DEVELOPMENT IN VITRO BINDING/REACTIONS LUCIFERIN ADDITION AND EFFECTS IN VIVO TESTING/TRIALS Image removed due to copyright restrictions. “Firefly Luciferase antibody for ICC/IF (Rat)” by Mal Niladri. http://www.abcam.co.jp/index.html?pagecon fig=reviews&intAbID=21176&intAbReviewID =5843 QUESTIONS REMAINING QUESTIONS POSSIBILITY OF REJECTION LUCIFERIN EFFECTS TAXING ON BODY DEGRADATION DELAY SAFETY O O H N H N N H O H O NH H2N + NH2 Figure by MIT OpenCourseWare. QUESTIONS REMAINING QUESTIONS SECURITY DESIGNED TO SURVIVE IN HUMAN POSSIBLE TOXIN DELIVERY SHOULD NOT MAKE PUBLIC T-CELL ENGINEERED TO DIE Electron microscope image removed due to copyright restrictions. image source: http://www.ncc.go.jp/ Courtesy of the National Cancer Center (Japan). Used with permission. WOULD IT SELL WOULD SUNK COSTS CCD CAMERA: ~$3,000 RIBOZYME SEQUENCING: $100+ RECEPTOR PLASMID AND LUCIFERASE PLASMID: $1000+ FIXED COSTS T-CELL HARVESTING: ~$700 DNA TRANSFECTION: ~$300 LUCIFERIN DOSE: $400 PER GRAM WOULD IT SELL WOULD EFFECTIVENESS GRADIENT OF LIGHT DYNAMIC OVER A PERIOD OF TIME SCALE AND 3D CLARITY COMPETITION STATIC TESTS CTC/TMEM BLOOD TESTS LYMPH NODE SCREENING IN SUMMARY OUR PROBLEM OUR CANCER DEATHS DUE TO METASTASIS LACK OF KNOWLEDGE NO ACCURATE, DETAILED TESTING OUR SOLUTION ACTIVE MAPPING OF METASTASIS SHOWS PROBLEM AREAS GIVES SENSE OF HOW/WHEN IT TRAVELS THANKS TO… NATALIE KULDELL AGI STACHOWIAK MENTOR “RA” (anonymous) CHRISTINA SMOLKE DREW ENDY CHRIS ANDERSON ROGER KAMM FOR THEIR HELP! FOR MIT OpenCourseWare http://ocw.mit.edu 20.020 Introduction to Biological Engineering Design Spring 2009 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms. ...
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