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Project Ubermensch

Project Ubermensch. A Leap Towards Regeneration. Regeneration. Imagine a world … Organs Limbs Spinal cord. Seems like science fiction But in Reality…. Many organisms can!. Salamanders, zebrafish, planarian flatworms. Salamander Limb Regeneration.

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Project Ubermensch

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  1. Project Ubermensch

  2. A Leap Towards Regeneration

  3. Regeneration • Imagine a world … • Organs • Limbs • Spinal cord Seems like science fiction But in Reality…

  4. Many organisms can! • Salamanders, zebrafish, planarian flatworms

  5. Salamander Limb Regeneration

  6. So, if they can do it… why can’t we? We can… but only up to a certain point

  7. The Basis of Regeneration Wound healing • Wound Epithelium • Cellular dedifferentiation • Naturally turn back cellular clock • Proliferation

  8. Proposal • Investigate genetic pathways and specific regulators of the dedifferentiation pathway in the salamander model • Manipulation of specific regulators in orthologous human pathways  dedifferentiation in human cells?

  9. The Importance • Fundamental understanding of pathways give insight into control of dedifferentiated cells • Regenerative pathways – scar tissue vs. redevelopment- one piece to the puzzle

  10. The Impact • Treatment for many diseases • Help in tissue regeneration research • Development of disease specific materials • Insight into natural regenerative processes human regeneration

  11. Competing Technologies • Induced pluripotent stem cells (Yu et al. 2007) • Epigenetic reprogramming • Clinical research of pluripotent stem cells

  12. Knowns Unknowns • Induce pluripotency in human somatic cells • Nerve-dependent regeneration/ neurotrophic factor signaling (Kumar et al. 2007) • Salamander genome • Control of induced pluripotent stem cells - cancerous • Degree of pluripotency • Self assembly of cell lines into tissues

  13. Chitinase-erase Food Allergies: When your immune system reacts against a harmless compound found in what you eat.

  14. Chitinase? What and Why? • Plant defense: Chintin-ases breakdown fungi and some bacterial cell walls • Expressed in low amounts—0.01% in grains is “substantial” • Increase in production-exposure to chitin, chitosan, ethylene • Increase Latex-Fruit syndrome due to our current ripening process with ethylene gas

  15. Importance: Latex-Fruit Syndrome • Chitinase causes “Cross-reactive allergen” with Latex -hevein-like domain at the N termius • 1-6% of the population suffers from Latex allergy • Latex-Fruit Allergy: 30-50%

  16. Importance: Treatment of Severe Allergies Due to B cell/antibody sensitivity to specific antigens in a particular food. • Recognition of Epitope • Histamine release • Anaphylatic shock • Possible Death • EpiPens: a large dosage of Epinephrine

  17. Competing Technology:Medicinally • IgE Neutralization: Omalizumab -monoclonal antibody -mainly for allergenic asthmatics • Immunotherapy: -exposing bits of allergenic substances to the body, increasing the concentrations over time -either shots or small bits of food

  18. Proposal Temporary Knockout of Chitinase before harvesting Control of Knockout through an environmentally sensitive promotor Indicator that confirms Chintinase knockout Feedback mechanism even after harvest

  19. Knowns: Current Plant Technologies • Insertion of Recombinant DNA-plants -Ti Plasmid -Gene gun • Temporary knockout of proteins: -RNAi -Transcription Repressors • Plants have stem cells—can develop into an entire organism from a few cells

  20. Unknowns • Chitinase protein production pathway • Control of Promotor • Developing an entire plant • Progeny that does not need infection • Would it be safe to eat? Taste the same?  Accepted by Public?

  21. Impact • Allergy-free or hypoallergenic foods: more food options • Same technology- eliminate or enhance certain chemicals in plants and even other organisms

  22. Want Milk? The purpose of this project is to allow lactose intolerant individuals to consume dairy products without having to ingest lactase with every ingestion of dairy. (1)

  23. Want Milk? Lactose intolerance affects 70-75% of people worldwide, with its prevalence varying by ethnicity. (2)

  24. Want Milk? General Plan of Action -Create a gene that codes for lactase and insert it into Bifidobacterium Bifidum -The bacteria will then begin producing lactase -Find a way to insert new bacteria into GI tract, such as direct ingestion. Potential medium: yogurt -Possibility of bacterial conjugation

  25. Want Milk? This project would have a great impact worldwide if it was successful. Only 10% of Americans suffer from lactose intolerance, but success would improve the lives of over 70% of the world’s population

  26. Want Milk? Competition Lactaid and other brands make lactase that can be ingested with a meal, as well as lactose-free dairy products. (3)

  27. Want Milk? Knowns: -Lack of ability to produce lactase causes lactose intolerance -B. Bifidum is beneficial to our health and digestion, is found in almost everyone, stays in the lower GI tract, is immobile, and safe to use -Lactase can be/has been produced through biological methods

  28. Want Milk? Unknowns: -Whether the B. Bifidum would stay in the GI tract once it is introduced -What signals to use to trigger and halt enzyme production -Whether it is possible for the bacteria to produce sufficient amounts of lactase

  29. Sources A Leap Towards Regeneration? Resources • Picture: http://artfiles.art.com/5/p/LRG/8/892/IENJ000Z/tree-frog.jpg tree frog (Intro slide) • Pictures: newswiseblog.blogspot.com/2009_05_01_archive.html Background of Earth • www.bountyfishing.com Picture of axolotl • http://webscript.princeton.edu/~icouzin/website/wp-content/uploads/image/zebra-fish-61290.jpg Picture of zebrafish • http://www.mdc-berlin.de/en/news/2009/20090721-international_research_team_seeks_to_unrav/index.html Picture of planarian flatworms • http://animals.nationalgeographic.com/staticfiles/NGS/Shared/StaticFiles/animals/images/1024/axolotl.jpg Picture of axolotl • http://th09.deviantart.net/fs24/300W/f/2008/010/f/1/__Blind_Salamander_Protocol___by_XOTV.jpg Picture of cartoon salamander • http://www.foxnews.com/images/325524/1_61_stemcells320.gif Picture of induced pluripotent stem cells Articles: • Nishikawa, S., R.A. Goldstein, and C.R. Nierras. "The Promise of Human Induced Pluripotent Stem Cells for Research and Therapy." Nature Reviews Molecular Cell Biology. 9.Sept. (2008): 725-729. • Yu, J. et al. "Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells." Science. 318.Dec. (2007): 1917-1920. • Kragl, M. et al. "Cells Keep a Memory of Their Tissue Origin During Axolotl Limb Regeneration." Nature. 460.July (2009): 62-66. • Kumar, A. et al. "Molecular Basis for the Nerve Dependence of Limb Regeneration in an Adult Vertebrate." Science. 318.Nov (2007): 772-777.

  30. Sources continued… Chitinase-erase • Picture of Payaya (intro slide) : http://www.thedailygreen.com/cm/thedailygreen/images/xw/papaya-clean-FD-lg.jpg • Picture of Xolair (Omalizumab): http://2.bp.blogspot.com/_otrvz2aDOLk/R1F3Uc_hYjI/AAAAAAAAAB8/0JqWKUDnQB0/s1600-R/Xolair.jpg • Picture of Latex glove: http://en.wikipedia.org/wiki/File:Disposable_gloves_09.JPG • Picture of avocado: http://en.wikipedia.org/wiki/File:Avacado444.jpg • Picture of N terminus hevein domain: http://dmd.nihs.go.jp/latex/cross-e.html • Picture of plant callus: http://upload.wikimedia.org/wikipedia/commons/thumb/1/18/Callus1.jpg/220px-Callus1.jpg • Picture of GUS reporter: http://upload.wikimedia.org/wikipedia/commons/thumb/9/9c/Rice_embryo.png/220px-Rice_embryo.png • http://books.google.com/books?hl=en&lr=&id=MxFn0gNqEWMC&oi=fnd&pg=PA157&dq=+%22Gooday%22+%22Agressive+and+defensive+roles+for+chitinases%22&ots=yitZdTSGMH&sig=6C0KXm93mM3NLu2a0-R9JWIUx_0#v=onepage&q=&f=false Articles: • Paul P. Belliveau. "Omalizumab: A Monoclonal Anti-IgE Antibody." MedGenMed. 2005; 7(1): 27. • Elizabeth Landau. “'Exciting' advance reported in peanut allergy therapy.” CNN. February 19, 2010. http://www.cnn.com/2010/HEALTH/02/19/aaas.food.allergies/index.html • R. A. Jefferson. The GUS Reporter Gene System. Nature 342, 837 - 838 (14 December 1989). • http://www.nature.com/nature/journal/v342/n6251/abs/342837a0.html • Wagner, S. and Breiteneder, H.: “The latex-fruit syndrome.” Biochem. Soc. Trans., 6, 935-940 (2002) http://www.ncbi.nlm.nih.gov/pubmed/12440950?dopt=Abstract • Website on Latex-Fruit Syndrome: http://dmd.nihs.go.jp/latex/cross-e.html

  31. Sources continued… Want Milk? • Websites Visited: • http://en.citizendium.org/wiki/Bifidobacterium_bifidum • http://www.textbookofbacteriology.net/normalflora.html • http://www.wrongdiagnosis.com/l/lactose_intolerance/prevalence.htm • Picture Credits: • (2)http://www.dsm.com/le/en_US/maxilact/html/lactose_intolerance.htm • (3)http://www.lactaid.com • (1)http://oregonstate.edu/dept/foodsci/dairy/dairy_links.htm • (Introduction): http://badanimalpuns.files.wordpress.com/2009/12/cow.jpg

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