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Essay 1


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Essay 1

  1. 1. <ul><li> p/u/0/djFb8PGS34g </li></ul>
  2. 2. Compare and contrast the Drosophila and Zebrafish as animal systems for the study of human disease. April, Laura, Alaa
  3. 3. What’s an Animal System? <ul><ul><li>An animal system is a living, non-human animal used for the research and investigation of human disease </li></ul></ul>
  4. 5. Drosophila Melangaster
  5. 6. Drosophila Melangaster <ul><li>Fruit fly </li></ul><ul><li>One of the first to be used </li></ul><ul><li>Similarities to human genes </li></ul><ul><li>Used for high throughput drug screening </li></ul>
  6. 7. Advantages <ul><li>Fast development </li></ul><ul><li>Carry out sophisticated loss-of-function and gain-of-function genetic analysis </li></ul><ul><li>Easy and rapid genetic analysis </li></ul><ul><li>Short generation time </li></ul><ul><li>High fecundity </li></ul><ul><li>Easy maintenance in large numbers </li></ul><ul><li>Mutants are easier to obtain </li></ul>
  7. 8. Neurodegenerative Diseases <ul><li>Generation of transgenic Drosophila which over express mutated proteins causing them to develop degenerative diseases allowing us to use them as models for Alzeimers and Huntingtons disease. </li></ul><ul><li>Animal models have helped us find possible cause of HD: (1) Expansion of unstable CAG repeat (2) Effect of Quasi-pure polyglutamine tracts (3) Implications to Caspases 1 & 3 </li></ul>
  8. 9. Parkinson’s disease <ul><li>Disease background: -Progressive degenerate disorder of the CNS -Idopathic disorder -Symptoms are movement related -Dominant cause = mutations of alpha synuclein </li></ul><ul><li>Animal model: -Flies with mutant alpha synuclein have developed motor impairment -Research on Parkin specific mutations in association with indirect fly muscles </li></ul>
  9. 10. Spinal Muscular Atrophy (SMA) <ul><li>Disease background: -Characterised by degeneration of motor neurons -Mutation of Survival Motor Neuron(SMN) gene in humans </li></ul><ul><li>Model: -Model mimics phenotype of human disorder -The Fibroblast Growth Factor (FGF) signalling pathway in humans is the homolog to the drosophilas’ SMN -SMN gene mutation results in: 1)Reduced viability 2)Decreased motility 3)Develops muscular atrophy in the adult thorax </li></ul>
  10. 11. Heart Disease <ul><li>Disease background -Umbrella term for many heart related diseases -Leading Cause of death in the UK -Examples: CHD, Cardiovascular disease and Heart failure. </li></ul><ul><li>Animal Model -New research field -Less complicated circulatory system than in humans -From screening 7,061, 500 were found to be associated with cardiovascular disorders </li></ul><ul><li>-Mutant flies have low levels of PE -Initiate a new mechanism for synthesising fats -This is the protein SREBP which activates enzymes that synthesise fats -High levels of this protein along with triglycerides and heart damaging fats. -Fat accumulation and distribution to the membrane leads to heart problems. -Inhibiting this protein allows restoration of fat balances and therefore reduced heart malfunctions. </li></ul>
  11. 12. Zebrafish
  12. 13. Zebrafish <ul><li>Danio rerio </li></ul><ul><li>Tropical freshwater fish </li></ul><ul><li>Genetically and morphologically similar to humans </li></ul><ul><li>Good human disease models </li></ul>
  13. 14. Advantages <ul><li>Short generation time (especially for a vertebrate) </li></ul><ul><li>Transparent embryo </li></ul><ul><li>Genetic tractability </li></ul><ul><li>Easy manipulation </li></ul>
  14. 15. Spinal Muscular Atrophy(SMA) <ul><li>The Morpholino Spinal Motor Neuron(SMN) protein gene is the faulty gene is some forms of SMA </li></ul><ul><li>This has been researched using gene knockdowns of the SMN gene in Zebrafish embryos </li></ul><ul><li>Morphant axons exhibit motor axon specific pathofinding defects with no increase in the rate of apoptosis in motor neurons. </li></ul><ul><li>Concluding - SMN has an important function in motor axon development and maintenance </li></ul>
  15. 16. Heart Disease <ul><li>Special ability to regenerate damaged heart </li></ul><ul><li>Our capability of developing our heart once should mean we can do it again? </li></ul><ul><li>Fast heart development - 12 hours </li></ul><ul><li>Transparent embryo allows viewing of heart and blood vessel development </li></ul><ul><li>Similarities in key genes and chemical messengers means we can try to replicate the process in humans </li></ul>
  16. 17. Drosophila Vs. Zebrafish Zebrafish Zebrafish
  17. 18. Compare <ul><li>Both have high Fecundity </li></ul><ul><li>Both used for drug discovery </li></ul><ul><li>Both develop rapidly - Allowing rapid genetic analysis </li></ul><ul><li>Embryos develop outside and not in the mother therefore developmental stages can be monitored </li></ul><ul><li>Easy access with fewer ethical objections </li></ul>
  18. 19. Contrast <ul><li>Invertebrate </li></ul><ul><li>7-19 generation time </li></ul><ul><li>Micromanipulation is limited </li></ul><ul><li>Non-transparent embryo </li></ul><ul><li>DNA content - 180 million </li></ul><ul><li>58% genetic similarity to humans </li></ul><ul><li>Vertebrate </li></ul><ul><li>3-4 months generation time </li></ul><ul><li>Micromanipulation is greater </li></ul><ul><li>Transparent embryos </li></ul><ul><li>DNA content - 1900 million </li></ul><ul><li>82% genetic similaritiey to humans </li></ul>Drosophila Zebrafish
  19. 20. Conclusion - why we think Zebrafish are better models. <ul><li>Zebrafish is a more reliable study for heart disease </li></ul><ul><li>They are vertebrates </li></ul><ul><li>Greater genetic similarities </li></ul><ul><li>Similar organ systems </li></ul><ul><li>Similar developmental pathways </li></ul><ul><li>Females are easier to work with as they are larger </li></ul>
  20. 21. References <ul><li>Peter.J.Russel. Essential I-Genetics (first edition) Pearson education </li></ul><ul><li>Griffths, Miller, Suzuki, Lewontin & Gelbart An introduction to genetic analysis (7th edition) W.H.Freeman </li></ul><ul><li> / British heart foundation </li></ul><ul><li>Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling Anindya Sen 1 , Takakazu Yokokura 1 , Mark W. Kankel 1 , Douglas N. Dimlich 1 , Jan Manent 1 , Subhabrata Sanyal 2 , and Spyros Artavanis-Tsakonas 1,3 </li></ul><ul><li>Richard Butler In vivo analysis of neurological disease mechanisms in zebrafish. Thesis 15014 </li></ul><ul><li> </li></ul><ul><li> </li></ul><ul><li>http://pubs.acs. org/subscribe/journals/mdd/v07/i06/html/604 feature_ma.html </li></ul><ul><li> ent/9/2/99.long </li></ul><ul><li> </li></ul><ul><li> </li></ul>
  21. 22. Q & A