Lessons from Model Organisms Flashcards

1
Q

What are the advantages of Saccharomyces cerevisae (yeast) as a model organism?

A

Cheap

Best genetics

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2
Q

What is a disadvantage of Saccharomyces cerevisae (yeast) as a model organism?

A

Unicellular fungus - may not age in same way as animal

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3
Q

What are the advantages of Caenorhabditis elegans as a model organism?

A

Cheap
Shows real ageing
Short lifespan - fast experiments
No inbreeding effects

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4
Q

What is a disadvantage of Caenorhabditis elegans as a model organism?

A

Not mammal - findings may not apply to humans

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5
Q

What are the advantages of Drosophila melanogaster as a model organism?

A

Short lifespan - fast experiments

Organ complexity and genes closer to mammals than in C. elegans

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6
Q

What are the disadvantages of Drosophila melanogaster as a model organism?

A

Inbreeding effects

More expensive than C. elegans

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7
Q

What are the advantages of Mus musculus as a model organism?

A

Mammal

Good genetics

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8
Q

What are the disadvantages of Mus musculus as a model organism?

A

Long lifespan - slow experiments

Very expensive

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9
Q

What are inbreeding effects?

A

Inbreeding increases homozygosity for recessive mutations that shorten lifespan in population
Confounding variable in lifespan studies

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10
Q

Is ageing monogenic or polygenic?

A

Polygenic

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11
Q

What type of protein does Target of Rapamycin (TOR) encode?

A

Protein kinase

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12
Q

Name the mammalian TOR complexes

A

mTORC1

mTORC2

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13
Q

What is the effect of rapamycin?

A

Inhibits mTOR

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14
Q

How does long-term mTORC1 inhibition affect mTORC2 activity?

A

Indirectly

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15
Q

When are mTORC1 and mTORC2 activated?

A

Under favourable conditions

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16
Q

What does mTORC1 respond to?

A

Growth factors

O2

17
Q

What is the effect of mTORC1 activation?

A

Increased protein synthesis, decreased autophagy - cell growth

18
Q

What does mTORC2 respond to?

A

Growth factors

19
Q

What is the effect of mTORC2 activation?

A

Increased survival and proliferation

20
Q

What is the overall effect of TORC1 inhibition?

A

Lifespan extension

21
Q

Define replicative lifespan

A

Capacity of cell to produce progeny

22
Q

Define chronological lifespan

A

Capacity of cell to survive in quiescence

23
Q

What is the effect of TOR1 KO in yeast?

A

Increases replicative and chronological lifespan

24
Q

How does RNAi work?

A

Short RNAs guide RISC complex to target mRNA - cleaves - prevents translation

25
Q

Why might the lifespan extension have been larger in TOR KO C. elegans than in TOR RNAi?

A

RNAi given after development - some TOR protein made early

RNAi has lower efficiency at preventing protein formation than KO - partial gene inhibition

26
Q

How does the GAL4/UAS binary transgenic system work?

A

One line with GAL4 transcription factor - under tissue-specific promoter
One line with transgene - under promoter containing UAS sequences
In progeny - transgene only expressed in cells expressing GAL4 - tissue-specific transgene expression

27
Q

What is the effect of using GAL4/UAS to express a TOR inhibitor in a single tissue in Drosophila?

A

Increases lifespan

28
Q

What is the effect of a heterozygous mTOR KO in mice?

A

Increases lifespan

29
Q

What are the roles of TORC1?

A

Translation regulation
Metabolism
Protein turnover - blocks autophagy and proteasome assembly

30
Q

What does the translation regulation role of TORC1 support?

A

Gene hyperfunction theory

31
Q

What does the protein turnover role of TORC1 support?

A

Damage/maintenance theory

32
Q

What is the effect of TORC1 inhibition in multiple species?

A

Increases lifespan

33
Q

How does TORC1 inhibition increase lifespan?

A

Unknown

Probably due to effects on multiple pathways