In any bar, if I tell people that I work on worms their eyes glaze over. When I say I’ve been doing that for ten years and more, I get looks of pity. If I ever go on to say that I think worms are totally cool, like humans only simpler and easier, then people edge away quietly leaving me alone with my beer. So why do I work on this tiny animal?
I work on worms because I like simple, stripped-down models that I can play with easily. The worm is very basic — each adult has only 959 cells and we know every cell division that occurs during its development. Despite its simplicity of form, the worm is genetically complex — the worm has 20,000 genes, half of which have very close matches in humans. So here’s the problem: we know all the genes and we know the whole of development — what does each gene do and how do they all cooperate to make a correct functioning animal? And here’s the magic — using a technique called RNAi, we can switch off any one of the worm’s genes at any stage of development and look at the effect on the animal. RNAi is miraculously easy to carry out, and so we can play with the worm simply and quickly, taking out the 20,000 genes one by one and looking at the effects.
Ultimately, fun as it is to mess around with worms, what we care about is humans. The central question that interests us is this — if you knew your entire genome sequence, what would it tell you? Can you predict your chances of getting bowel cancer, or of having an adverse reaction to a drug? At present, the answer is an emphatic no. How does our work in the worm help with this problem? In the worm, since we can use RNAi to remove each gene in turn and see the precise effect on the ‘health’ of the worm, we can begin to learn how to predict how inherited mutations will affect health in humans. We study not only how to predict the effect of removing any individual gene (which we can now do with surprising accuracy), but also the effect of removing combinations of genes. Since there are ~3million differences between any human genomes, knowing how multiple mutations combine to affect our health and risk of disease is one of the major problems in modern genetics.
For more information on my work, please visit my homepage: www.fraserlab.org
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