Model Organisms

Model Organisms
Model 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