The Record 2009 - Keble College - University of Oxford

The Life of the College
My main research at present is devoted to understanding how
the tiny worm is able to deal with bacterial infections. There
are vastly more bacteria in the world than all other kinds of
organism — animals, plants, fungi, protozoa and so on — put
together. Every animal is exposed to a great variety of bacteria,
many of which have the potential to cause disease. The problem
of survival is acute for C. elegans, because it lives by feeding on
bacteria in its natural habitat, garden soil and rotting vegetation.
Moreover, worms can’t make antibodies, so they cannot acquire
immunity to pathogens in the same way that vertebrates such as
humans do.
It is now realized there are two kinds of immunity, called
adaptive immunity and innate immunity. Adaptive immunity is
found only in vertebrates, and allows them to become immune
to novel pathogens, such as new strains of influenza, if they are
able to survive a first encounter with the virus. But surviving
that first encounter depends on the other kind of immunity,
innate immunity, which provides a cruder and more generic
defence against bacteria and viruses. Innate immunity is ancient
in evolution and hard-wired in the genome. It is increasingly
seen as profoundly important in providing the first line of
defence against disease in mammals, and for invertebrates it is
the only game in town.
The strategy of innate immunity is to recognize the presence
of a bacterial or viral invader by detecting one of the general
features shared by many pathogens, and to respond by
activating general defences, such as the production of chemicals
that will kill, inhibit or delay the invaders. There is much
interest and mystery in both steps of this strategy. First, how
does an organism realize that it is under attack and what are
the features of a pathogen that are recognized? Second, what
are the compounds that are produced in response, which can
act as broad-spectrum antibiotics? This is a neat trick. Perhaps
invertebrates such as nematodes and insects have evolved
particularly potent ways to kill bacteria, and these could
be developed into new kinds of medically useful antibiotic,
which are urgently needed. A further reason to be particularly
interested in nematode immunity is that nematodes, as a group,
seem to be resistant to all known viruses, in contrast to almost
all other kinds of animal. How have they managed this?
Investigating the warfare between C. elegans and bacteria, which
provide both food and threats to the worm, has wider relevance
in comprehending the whole biology of this organism. The
worm is simple enough in cell number and tissue complexity to
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