Krishanpal Karmodiya Template SlideShareAdhweat Gupta krishiiserpuneacin httpwwwiiserpuneacinkrish A model organism is a nonhuman species that is extensively studied to understand particular biological phenomena with the expectation that discoveries made in the organ ID: 493798
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Slide1
An Introduction to Model Organisms
Krishanpal
Karmodiya
Template: SlideShare-Adhweat Gupta
krish@iiserpune.ac.in
http://www.iiserpune.ac.in/~krish/Slide2Slide3
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? Slide4
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. Slide5
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 humansSlide6
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.Slide7
Bacteria: Unicellular, prokaryotes
Model OrganismsSlide8
Bacteria EverywhereSlide9
Bacteria in Air
Hemalatha
RaoSheetal
Gianchandani
Ankit
Jaiswal
Slide10
Bacteria under the microscope
Will be covered in one of the
practicalsSlide11
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?Slide12
Bacteria as a Model Organism
The foundations of
molecular biology
were based on studies of bacteria.
Antibiotics
Recombinant DNA technologiesSlide13
Bacteria
Yeast: Unicellular, eukaryotes
Model OrganismsSlide14
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.Slide15
Bacteria
Yeast
Hydra:
Multicellular
, Eukaryotes,
Invertebrate (Emerging Model System)
Model OrganismsSlide16
Phylogeny
Multicellularity
True tissues,
Germ layersSlide17
Hydra
Enormous regeneration capacitySlide18
The Power of RegenerationSlide19
Anatomy of
Hydra
Live in water
Most have tentacles
Catch food with stinging cells
Gut for digesting
Nerve net found throughout body Slide20
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 HydraSlide21
Bacteria
Yeast
Hydra
Model Organisms
C.
elegans
Slide22
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.Slide23
C.
elegans
Life Cycle and Research
Developmental
biology and Cell biology
Neurobiology
3. Aging
4. Human disease studies
(~75% of human disease genes have potential
C.
elegans
homologs
).Slide24
Bacteria
Yeast
Hydra
Model Organisms
C.
elegans
DrosophilaSlide25
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.Slide26
Life Cycle of Drosophila Slide27
MutationsSlide28
Bacteria
Yeast
Hydra
Model Organisms
C.
elegans
Drosophila
ZebrafishSlide29
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.Slide30
Development in
ex vivo
.Entire initial development is transparent.
48hrs is enough for the development of most of the organ systems.
Danio
rerio
(
zebrafish
)Slide31
Bacteria
Yeast
Hydra
Model Organisms
C.
elegans
Drosophila
Zebrafish
Chick -EmbryoSlide32
Chick Embryo
The chick embryo provides an excellent model system for studying the development of higher vertebrates wherein growth accompanies morphogenesis.
Courtesy-Google imagesSlide33
Chick Embryo Development
Courtesy-Google imagesSlide34
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. 2004Slide35
Demonstration: Chick Embryo Slide36
Bacteria
Yeast
Hydra
Model Organisms
C.
elegans
Drosophila
Zebrafish
Chick Embryo
MouseSlide37
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)Slide38
Arabidopsis thaliana
(thale cress)
Model OrganismsSlide39
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 healthSlide40
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 MessageSlide41
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
WormSlide42
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 OrganismsSlide43
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 OrganismsSlide44
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 OrganismsSlide45
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 OrganismsSlide46
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