term 2 Lecture 7: Model organisms (and why they're useful) Flashcards
model organisms
Using one type of organism to understand others, this is possible because all life is related by a common ancestor, shares genetic code and consists of similar biochemical building blocks.
Model organism examples
Drosophila melanogaster (fruit fly)
Escherichia Coli bacterium (E. coli)
Caenorhabditis elegans (nematode worm)
Arabidopsis thaliana (Thale-cress plant)
Mus musculus (house mouse)
Saccharomyces cerevisiae (Baker’s yeast)
Key characteristics
- easy to work with in labs (small/easy to grow/ house)
- rapid life cycles
- easy to cross/ breed
- large numbers of progeny
- diploid
- small & well characterised genomes ( model organisms have their genomes sequenced)
- easy to genetically modify (make transgenics)
- large number of mutants available
other considerations: - relevance & ethics
E. coli discovery and related Nobel prizes
a vehicle for cloning reactions
-Theodor Escherich (born 1857) German pediatrician discovered E. coli while investigating the physiology and pathology of the digestive tract
Nobel prizes for work with E. coli:
-1958 Lederberg, J. discovery of genetic recombination and organisation of genetic material of bacteria.
-1965 Jacob, F, Lwoff, A & Monod, J. elucidation of genetic control of enzyme and virus synthesis
-1969 Delbruck, A, Hershey, A, Lucia, S. the replication mechanism and genetic structure of viruses
why E. coli is a model organism
-rapid reproduction (asexually), dividing every 20 minutes
- one cell can form a colony (billions of cells)
- easy to grow on petri dishes/ in growth media
Genome:
- 1 circular chromosome
- 4.64 million bp
- 4300 genes
- 8% of genes in common with humans
- genome sequenced in 1997
(for reference: human genome has 3230 million bp, 23 chromosomes and 50,000-140,000 genes)
E. coli as a tool for cloning
almost universally used for the first step in a recombinant DNA experiment ( DNA inserted into E. coli plasmid, E. coli cultured and lysed to extract replicates)
- used a lot in biomedical research (code red) about 24% of biopharmaceuticals are produced in E. coli
many medicines and drugs are proteins
e.g. insulin to treat diabetes
erythropoietin to treat anemia
growth hormones to treat growth disorders.
^ bacteria such as E.coli are used as ‘bio factories’ to produce these. insulin was the first protein to be produced commercially in bacteria in 1978. A version of the human gene that encodes insulin was cloned and introduced into E.coli. Within 4 years bacteria-produced insulin was commercially available as a treatment for diabetes.
Saccharomyces cerevisiae ( Baker’s yeast)
- the simplest eukaryotic organism
- unicellular, can be grown in a similar way to bacteria ( on agar plates)
- easy to genetically modify
- contains a plasmid (2 microns) that can be used as a cloning vector
- bacterial plasmids can also be expressed in yeast
- exists in both haploid and diploid forms which makes it useful for genetic studies
- contains many of the same genes as the humans
genome:
16 pairs of chromosomes
6144 genes
12 million bp
25% genes in common with humans
genome sequenced in 1996
Relevance of bakers yeast in human disease (biotech code red)
it can be used as a model system for human disease e.g. Huntington’s Disease which results from a protein mutation forming aggregates is linked to many other brain diseases. HD is caused by mutant huntingtin protein (mHTT) that is aggregation prone - mHTT is expressed in yeast cells to study why it is cytotoxic (causes cell death.) Yeast expressing mHTT can be used to screen HD drug treatments.
use in medical biotechnology ( code red)
- used to produce recombinant proteins that are folded correctly and glycosylated ( sugars added) similar to the proteins of mammalian cells
^ prokaryotes cannot fold and glycosylate proteins this is something only eukaryotes are capable of
Relevance of bakers yeast in improving efficiency of industrial processes (Biotech code white)
- used to make bread and beer
- new strains are being developed to produce bioethanol ( for use as fuel) from a wide range of materials e.g. starch, lignin, cellulose and seaweed.
C. elegans as a model organism
- member of the nematode family
- a small transparent worm that lives in the soil
- the most abundant organism on earth
- free living in soil ( some nematodes are pathogenic to plants and animals)
- C. elegans consumes bacteria and lives in microbe rich environments such as rotting leaves and fruit
Genome:
-5 pairs of chromosomes
- 2 sex chromosomes in the female and one in the male
- 103 million bp
- 20500 genes
- genome sequenced in 1998
Growing C. elegans:
- they are small (1mm) and can be grown on petri-dishes with E.coli for food
- short generation time (3 days)
- females produce up to 1000 eggs
- easy to genetically manipulate by direct DNA injection
- females are hermaphrodites so recessive mutants can be produced easily
- transparent body therefore excellent for cell imaging
- model system for behavioural, developmental, aging studies
- stereotypic development - highly predictable, known no. of cells
C. elegans as a tool for aging studies ( red biotech)
Weinkove, D. uses C. elegans to screen drugs for their effect on the aging process - live nematodes are always moving whilst dead nematodes stay still so its easy to calculate lifespan.
Weinkove developed a technology called ‘healthspan’ that quantifies the number of moving nematodes in a sample so that they do not need to be counted manually.
D. melanogaster ( fruit fly) as a model organism
Nobel prizes related to Drosophila:
1933 Hunt Morgan, T. chromosomes in heredity
1946 Joseph Muller, H. x-rays cause DNA mutation
1995 Lewis, E.B., Nusslein-Volhard, C, Wieschaus E.F. the genetic control of early embryonic development
2004 Axel, R. odour receptors and the organisation of the olfactory system
2011 Hoffman, J.A. activation of innate immunity
2017 Hall, J.C., Rosbash, M, Young M.W. molecular mechanisms controlling the circadian rhythm
drosophila are effective for human disease study and study of insect borne diseases such as malaria.
Culturing drosophila:
- small 2-3 mm - rapid lifecycle of 10 days
- easy to work with in lab - hundreds can be kept in small vials
- easy to cross and females lay up to 500 eggs
- easy to genetically modify by DNA microinjection into embryos
-large number of mutants available
- virtually every gene can be manipulated with the genetic tools currently available
Genome:
3 pairs of chromosomes plus X+Y
174 million bp
14000 genes
50% of genes in common with humans
genome sequenced in 2000
lifecycle: day 1: egg+ embryo days 2-5: larvae/maggots
days 6-10: pupa —> adult fly
DDrosophila as a tool in medicine (red biotech)
for almost every organ of the human body there is an equivalent match in flies (see images of human/fly body plans)
common genes regulate their development, organisation and function.
75% of human disease genes have counterparts in the drosophila genome.
Drosophila disease models include:
- cancer
- motor neuron disease
- Alzheimer’s
- Parkinson’s
- epilepsy
- diet and healthy aging
- sleep disorders including jetlag
- alcohol addiction
—> research at Durham on the effects of Rugby player head injuries is being carried out by mimicking the injuries in drosophila and monitoring its effects
Limitations in drosophila studies of human conditions:
e.g. in Alzheimer’s disease nerve cell decay mechanisms and possible treatments for this can be studied in drosophila but ‘personality loss’ a human aspect of the condition cannot be quantified in flies
Drosophila studies for how Anopholes mosquitos transmit malaria ( red biotech)
At Durham Lena Riabinas lab is researching how mosquitos sense human prey by scent signals from skin - study of odour receptors and the organisation of the olfactory system using drosophila. Researching potential ways to interfere with odour perception or ways to attract mosquitos away from human populations.
Experiments are done by studying which genes are activated (in the antenna and brain) when flies are exposed to particular odours
Mice as model organisms
- small, easy to house and breed in small cages
- short generation time compared to other mammals (8 weeks)
- large litters of 8-10 pups
- easy to genetically modify by microinjection into cells and then implantation into embryos
- large number of mutants available
- model system for human diseases and immunogenetics
Genome:
19 pairs of autosomes plus X+Y
2700 million bp
26762 genes
99% genes in common with humans
genome sequenced in 2002
major ethical considerations
(see national centre for replacement, refinement and reduction of animals in research)
There is a framework for performing humane animal research and it is embedded in national and international legislation and in the policies of organisations that fund or conduct animal research
