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Model Organisms
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Model OrganismsModel Organisms and Modelling Disease
Model Organisms
Non-human species that are extensively studied in order to understand range of biological phenomena
Data and theories generated through use of model are used to advance understanding of other organisms- that are
more complex or less accessible to experimentation
Aspects of Modelling Human Disease
Understanding underlying biological processes
o Identify physiological, genetic and
molecular basis
o Identify targets for diagnosis & therapy
Develop/ validate diagnostic markers
Develop/ validate treatments
o Drug development
Discovery
Refinement
Preclinical testing
Non- Animal Models for Human Disease
Cell free extracts- [enzyme activity]
Cell lines- often immortalised
Bacteria- Escherichia coli
Eukaryotes
o Green algae/ Plants- Arabidopsis thaliana [DNA methylation, protein turnover], Zea mays [transposons],
Chlamydomonas reinhardtii [flagella]
o Slime molds- Dicytostelium discoidium [chemotaxis]
o Fungi- Saccharomyces cerevisiae, Schizosaccharomyces pombe [cell cycle], Neurospora crassa [circadian clock]
Invertebrate Animals Models for Human Disease
Aplysia carlifornica -mollusc- associative learning
Caenorrhabditis elegans- roundworm
Drosophila melanogaster- fruitfly
Strongylocentrotus purpuratus- puple sea urchin- development
Ciona intestinalis- ascidian sea squirt- development
Vertebrate Models for Human Disease
Danio rerio- zebrafish
Oryzias Latipes – medaka- cancer
Xenopus laevis- African clawed frog- development
Gallus gallus- red jungle fowl- development
Mus musculus- house mouse
Rattus norvegicus- Norway rat- behaviour
Macaca mulatra- rhesus macaque- HIV, behaviour
Featured Model Organisms
Escherichia coli – gramnegative gut bacteria
Saccharomyces cerevisiae- budding yeast
Caenorrhabditis elegans- roundworm
Drosophila melanogaster- fruitfly
Danio rerio- zebrafish
Mus musculus- house mouse
Many are ‘domesticated’ and inbred
Lab conditions are artificial – could miss evolved phenotypes
, Example genetic adaptation to lab conditions:
o Non-invasive yeast growth
o Suppression of mating type switching in yeast
o Loss of melatonin production in mice
Balance ‘power’ vs ‘representation’
o Simpler models for highly conserved functions
o Higher level of conservation for drug vs mutation screening
Benefits of comparative approach
Escherichia coli as model
Small I-chromosome genome- 4.6Mbase, ~4500 genes
20 min doubling time at 37oC
Safe lab strain with lots of publicly available reagents
Grown on defined media- (an)aerobically- liquid& plates
Selectable markers & phenotypes
Phages
Ease of genetic manipulation, plasmids
Large active research community EcoCyc
Publicly available reagents
Cryopreservation is routine
Escherichia coli
Best characterised bacterium
o Unicellular
o Smaller size
o No membrane-bound organelles
Gram-negative gamma proteobacterium- 1-2 μm long
o Gram stain refers to thinner peptidoglycan cell wall
o Most common aerobe in lower mammalian intestine
4.6 Mbase genome- variable across strains
o Increased size in pathogenic strains- lateral gene transfer
Last common ancestor with Homo sapiens- 2.5 BYA
Relevance in relation to human microbiome and disease
Seminal discoveries in molecular biology
o Genetic code- Crick et al., 1961
o Transcription- Stevens, 1960
o Gene Regulation- Jacob et al., 1960
o DNA replication- Lehman et al,. 1959
o Life cycle of lytic & lysogenic bacteria viruses-
Ellis & Delbruck, 1939
o Restriction enzymes- Linne & Arber/Meselson &
Yuan, 1968
Tool for pharmacology & biotechnology
o Recombinant DNA technology
o Production of proteins
Medical applications
Structural Biology
o Production of other organic compounds
Biofuels
Industrial chemicals
Experimental model for evolution
o Random nature of mutations – Luria & Delbruck,
1943
o Adaptation and genome evolution
o Repeatability vs historical contingency-
Travisano et al., 1995
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