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An Introduction to Model Organisms
Krishanpal Karmodiya
Template: SlideShare-Adhweat Gupta
[email protected]://www.iiserpune.ac.in/~krish/
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?
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.
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
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.
Bacteria: Unicellular, prokaryotes
Model Organisms
Bacteria Everywhere
Bacteria in Air
Hemalatha RaoSheetal Gianchandani
Ankit Jaiswal
Bacteria under the microscope
Will be covered in one of the practicals
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?
Bacteria as a Model Organism
•The foundations of molecular biology were based on studies of bacteria.
•Antibiotics
•Recombinant DNA technologies
Bacteria
Yeast: Unicellular, eukaryotes
Model Organisms
Yeast as a Model OrganismEukaryotic 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 Nobelprizes were awarded for discoveries involving yeast.
Bacteria
Yeast
Hydra: Multicellular, Eukaryotes, Invertebrate (Emerging Model System)
Model Organisms
Phylogeny
Multicellularity
True tissues,Germ layers
Hydra
Enormous regeneration capacity
The Power of Regeneration
Anatomy of Hydra
Live in water
Most have tentacles
Catch food with stinging cells
Gut for digesting
Nerve net found throughout body
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
Bacteria
Yeast
Hydra
Model Organisms
C. elegans
C. elegans 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.
C. elegans Life Cycle and Research
1. Developmental biology and Cell biology2. Neurobiology3. Aging4. Human disease studies (~75% of human disease genes have potential C. elegans homologs).
Bacteria
Yeast
Hydra
Model Organisms
C. elegans
Drosophila
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.
Life Cycle of Drosophila
Mutations
Bacteria
Yeast
Hydra
Model Organisms
C. elegans
Drosophila
Zebrafish
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.
Development in ex vivo.
Entire initial development is transparent.
48hrs is enough for the development of most of the organ systems.
Danio rerio (zebrafish)
Bacteria
Yeast
Hydra
Model Organisms
C. elegans
Drosophila
Zebrafish
Chick -Embryo
Chick Embryo
The chick embryo provides an excellent model system for studying the development of higher vertebrates wherein growth accompanies morphogenesis.
Courtesy-Google images
Chick Embryo Development
Courtesy-Google images
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
Demonstration: Chick Embryo
Bacteria
Yeast
Hydra
Model Organisms
C. elegans
Drosophila
Zebrafish
Chick Embryo
Mouse
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)
Arabidopsis thaliana(thale cress)
Model Organisms
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
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
Relative strengths of Model OrganismsOrganism Advantages Limitations
Excellent genetics UnicellularPowerful second site screening No distinct tissuesPowerful molecular techniquesPossess all basic eukaryotic cell organellesCell cycle control similar to animals
Yeast
Excellent genetics Limited external morphologyHermaphrodites/self-fertilization Less similar to humanFast generation times Powerful molecular techniques (cloning, RNAi)Genome sequence completeFew cells: 959 cells and lineages knownMorphology fully characterized
Worm
Organism Advantages Limitations
Fly
Excellent genetics Embryological manipulations difficultGenome sequenced Targeted gene disruption still difficult, although possibleRNAi effectiveFast generation timeSecond site suppressor/enhancer screensPowerful molecular techniquesGenes can be easily clonedTransgenic animals easily generatedTargeted misexpression of genes in space and timeMosaic analysis: determine where gene actsLaser ablation of single cells possible
Relative strengths of Model Organisms
Organism Advantages Limitations
Zebrafish
Simplest vertebrate Not yet trivial to clone genesGood genetics Transgenics not trivialTransparent embryos No targeted gene disruptionEmbryo manipulations possibleOrgan systems similar to other vertebrates (e.g., eyes, heart, blood,gastrointestinal tract)Rapid vertebrate development
Relative strengths of Model Organisms
Organism Advantages Limitations
Arabidopis
Universal model plantSmall sizeRelatively short life cycleSmall, sequenced genomeTransformed easilyTransgenics
Embryological manipulationsnon trivial
Relative strengths of Model Organisms
Organism Advantages Limitations
Chick
Availability, low cost Limited geneticsAccessibility, outside of mother Genome sequencedGreat for embryological manipulation; transplants of tissueEasily transfected by avian retroviruses
Relative strengths of Model Organisms
Organism Advantages Limitations
Relative strengths of Model Organisms
Mouse
Mammals Classic “forward” genetics difficultOrgans 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 slowsame as for all mammalsLarge mutant collectionConstruction of chimeric embryos possibleAvailability of material at all stagesSource of primary cells for culture
