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Drosophila natural history• Originated in Africa• Probably spread by human activity• Now found most places where we live• Likes compost, rotting fruit, yeast• Some features conserved, others a reflection of its life
strategy• Harmless (mostly)• Most lab strains derived from isolates collected before 1940’s• Strains collected subsequently have P transposable elements
and can’t easily be used
Model Organisms - a trainspotter’s guide
E. coli Yeast Worm Fly Mouse Human
# Genes 4000 6000 19000 15000 30000? 30000?
Genome (Mb) 4.6 150 3000 300010012
# Neurons 0 (1) 302 105 1011
Where our pet flies live…
Mice - 75c/day150k$/yr
Flies ~ 20k$/yr(consumables and labour)
Can’t be stored frozen :-(Source: John Roote
Fly pushingEarly 1900’s - Drosophila contributes to our understanding of heredity
Mid 1900’s - Grows in popularity among developmental biologists
Homozygous lethal mutations can be kept indefinitely as heterozygous balanced stocks
1970’s - 1980’s - Molecular biology, cloning of Hsp, Hox
1970’s - 1980’s - Large screens for developmental mutants
1982 - Transformation by injection of marked P transposable element into syncytial embryos; transgenic flies identified by marker in F1
1988 - Easy mobilisation of P made possible by stable transposase-producing strains
What’s different?
• More gene redundancy in humans & mammals
• Some organisation of tissues and organs
• Cardiovascular system
• Acquired immunity (antibody response)
• We’re studying them, instead of them studying us
Fly Gene Disruption Projects• Based on transposable element insertion
• Allows further local mutagenesis
• Non-directed - like Venter’s sequencing strategy
• Not random
• ~ 15000 target genes
• include ~ 4000 vital genes
• Requires ~ 1 insertion per 8 kb
• Coverage perhaps 25% of that, more on their way into public domain
Other ways to make “mutants”
• EMS - still has its attractions• Targeted knockouts for reverse genetics• Imprecise excisions for reverse genetics• RNAi for reverse or forward genetics• Deletion kits in defined backgrounds• Ask a fellow flypusher
Getting round early lethality
• GAL4 x UAS-X for targeted expressionCan be used for regulated RNAi expression
Getting round early lethality
• GAL4 x UAS-X for targeted expression• Enhancer/suppressor screens• Mitotic clones (using FLP recombinase)
Getting round early lethality
• GAL4 x UAS-X for targeted expression• Enhancer/suppressor screens• Mitotic clones (using FLP recombinase)• Temperature-sensitive point mutations• RNAi screens in cultured cells
Shared biology - shared diseases
• Cancer
• Ageing
• Neurodegeneration
• Infectious disease
• Models for disease vectors
• Behaviour
• Do flies have disease-gene homologs?
• Do flies have basic cellular processes related to the disease?
• Be nice to a friendly fly geneticist
Flies and “your” disease
The future?
• More insertions• UAS-RNAi collections• SNPs, better mapping of point mutations• Temperature-sensitive alleles for cell biology• Screens take more work in flies than in worms• Some things only possible in flies and not worms -
physiology, some development, some cell biology• “Hopping in” takes about $20k investment, or a
friendly fly lab to drop in on
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