1. An Introduction to Model Organisms Krishanpal Karmodiya Template: SlideShare-Adhweat Gupta krish@iiserpune.ac.in http://www.iiserpune.ac.in/~krish/

3. A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. What are Model Organisms?

4. Common ancestry of all organisms resulting conservation of major aspects of biology. What makes Model Organisms possible? The basic operating principles are nearly the same in all living things.

5. Typical considerations while selecting Model Organisms  Rapid development with short life cycles  Small adult size  Ready availability and inexpensive maintenance and breeding  Tractability to experimental methodology  Biology being studied have relevance to humans

6. Basic Unit of Life : Cell  Prokaryotic and Eukaryotic Cells The fundamental properties of how cells grow and divide, how inheritance works, and how organisms store and use energy.

7. Bacteria: Unicellular, prokaryotes Model Organisms

8. Bacteria Everywhere

9. Bacteria in Air Hemalatha Rao Sheetal Gianchandani Ankit Jaiswal

10. Bacteria under the microscope Will be covered in one of the practicals

11. Exercise: Bacteria in your surroundings Make homemade agar plates and find out bacterial population in your finger nail, your hands, the door handle. Note the differences in colour, shape and other properties. More bacteria on the bathroom sink or on the TV remote? Try adding a drop of hand sanitizer on your growing plate. Do washed hands have less bacteria than unwashed hands?

12. Bacteria as a Model Organism The foundations of molecular biology were based on studies of bacteria. Antibiotics Recombinant DNA technologies

13. Bacteria Yeast: Unicellular, eukaryotes Model Organisms

14. Yeast as a Model Organism  Eukaryotic system.  Signaling molecules and cell cycle are nearly similar.  Good model system to understand many human diseases including cancer (Approx. 20% human disease genes have yeast homologues)  Ease of genetic manipulation allows its use for analyzing and functionally dissecting gene products from other eukaryotes.  Last decade four Nobel prizes were awarded for discoveries involving yeast.

15. Bacteria Yeast Hydra: Multicellular, Eukaryotes, Invertebrate (Emerging Model System) Model Organisms

16. Phylogeny Multicellularity True tissues, Germ layers

17. Hydra  Enormous regeneration capacity

18. The Power of Regeneration

19. Anatomy of Hydra Live in water Most have tentacles Catch food with stinging cells Gut for digesting Nerve net found throughout body

20. Phylogeny (At the base of metazoan phyla) Evolutionary transition (body axis, germ layers, gonads, cell types) Pattern formation (peculiar tissue dynamics make hydra a perpetual embryo) Regeneration, stem cells What we can learn from Hydra

21. Bacteria Yeast Hydra Model Organisms C. elegans

22. Caenorhabditis elegans (nematode round worm)  One of the best characterized multicellular animal at the level of genomics, genetics, embryology  Its genome is fully sequenced  C. elegans is unique in that it can be grown and genetically manipulated with the speed and ease of a micro-organism while offering the features of a real animal  C. elegans has a full set of organ systems, has complex sensory systems, shows coordinated behavior, and it is possible to trace the lineage of every one of its approximately 1000 constituent cells  RNAi and miRNA are discovered in worms. First use of GFP in animals.

23. C. elegans Life Cycle and Research 1.Developmental biology and Cell biology 2.Neurobiology 3. Aging 4. Human disease studies (~75% of human disease genes have potential C. elegans homologs).

24. Bacteria Yeast Hydra Model Organisms C. elegans Drosophila

25. Fruit flies (Drosophila)  A versatile model organism that has been used extensively for biomedical research.  Easy-to-manipulate genetic system and can be used to study development, physiology and behavior.  Biological complexity comparable to that of a mammal  Many organ systems in mammals have well-conserved homologues in Drosophila  Has provided new insights into forms of cancer, neurodegenerative diseases, behavior, immunity, aging, multigenic inheritance, and development.

26. Life Cycle of Drosophila

27. Mutations

28. Bacteria Yeast Hydra Model Organisms C. elegans Drosophila Zebrafish

29. Danio rerio (zebrafish)  Small size, short life cycle, ease of culture, and ability to readily produce mutations relevant to human health and disease  The embryonic development can be seen through its transparent egg and closely resembles that of higher vertebrates  Other shared features with humans include blood, kidney, and optical systems  In addition, its genome is half the size of the mouse and human genomes, which is valuable in identification of key vertebrate genes.

30.  Development in ex vivo.  Entire initial development is transparent.  48hrs is enough for the development of most of the organ systems. Danio rerio (zebrafish)

31. Bacteria Yeast Hydra Model Organisms C. elegans Drosophila Zebrafish Chick -Embryo

32. Chick Embryo The chick embryo provides an excellent model system for studying the development of higher vertebrates wherein growth accompanies morphogenesis. Courtesy-Google images

33. Chick Embryo Development Courtesy-Google images

34. Model systems and techniques 4day -chicken embryo stained for muscle specific gene expression Muscle precursor cells emigrating from the somites into limb bud labelled by GFP. Scaal et al. 2004

35. Demonstration: Chick Embryo

36. Bacteria Yeast Hydra Model Organisms C. elegans Drosophila Zebrafish Chick Embryo Mouse

37.  Closest mammalian model organism to humans  Genes that code for proteins responsible for carrying out vital biological processes in both the human and the mouse share a high degree of similarity.  Therefore, the mouse has already proven extremely useful in development, genetic, and immunology studies  Transgenics and KO’s possible  A great system for studying and understanding human disease, as well as a mechanism for investigating new treatment strategies in ways that cannot be done in humans Mus musculus (mouse)

38. Arabidopsis thaliana (thale cress) Model Organisms

39. Arabidopsis thaliana (thale cress)  Small flowering plant  Has a small genome relative to other plants and is easily grown under laboratory conditions  Amenable to some genetics particularly generation of transgenics  Allows insight into numerous features of plant biology, including those of significant value to agriculture, energy, environment, and human health

40. In any biological study, the choice of organism is critical – which organism we study will be determined primarily by the questions we want to answer. Take Home Message

41. Relative strengths of Model Organisms Organism Advantages Limitations Excellent genetics Unicellular Powerful second site screening No distinct tissues Powerful molecular techniques Possess all basic eukaryotic cell organelles Cell cycle control similar to animals Yeast Excellent genetics Limited external morphology Hermaphrodites/self-fertilization Less similar to human Fast generation times Powerful molecular techniques (cloning, RNAi) Genome sequence complete Few cells: 959 cells and lineages known Morphology fully characterized Worm

42. Organism Advantages Limitations Fly Excellent genetics Embryological manipulations difficult Genome sequenced Targeted gene disruption still difficult, although possible RNAi effective Fast generation time Second site suppressor/enhancer screens Powerful molecular techniques Genes can be easily cloned Transgenic animals easily generated Targeted misexpression of genes in space and time Mosaic analysis: determine where gene acts Laser ablation of single cells possible Relative strengths of Model Organisms

43. Organism Advantages Limitations Zebra fish Simplest vertebrate Not yet trivial to clone genes Good genetics Transgenics not trivial Transparent embryos No targeted gene disruption Embryo manipulations possible Organ systems similar to other vertebrates (e.g., eyes, heart, blood, gastrointestinal tract) Rapid vertebrate development Relative strengths of Model Organisms

44. Organism Advantages Limitations Arabidopis Universal model plant Small size Relatively short life cycle Small, sequenced genome Transformed easily Transgenics Embryological manipulations non trivial Relative strengths of Model Organisms

45. Organism Advantages Limitations Chick Availability, low cost Limited genetics Accessibility, outside of mother Genome sequenced Great for embryological manipulation; transplants of tissue Easily transfected by avian retroviruses Relative strengths of Model Organisms

46. Organism Advantages Limitations Relative strengths of Model Organisms Mouse Mammals Classic “forward” genetics difficult Organs homologous to human Early-acting mutant phenotypes difficult to study Reverse genetics: targeted KOs Embryonic manipulations difficult (inside mother) Developmental overview Development and life cycle slow same as for all mammals Large mutant collection Construction of chimeric embryos possible Availability of material at all stages Source of primary cells for culture