C.elegans

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Free living nematode

Tiny worms - hemaphrodites

Resistance problem particularly bad in sheep as drugs have been used in non-controlled ways = not been used to treat disease but to maximise production

*C elegans is a model organism for biological studies

excellent genetic, transgenic and genome tools available

very similar developmental pathways and cuticle structure to parasitic nematodes

transparent so can see tissues and organs - makes it a good model system

very rapid life cycle, and very easy to grow

can study genetics - can easily knock out genes etc.

first animal genome to be completely sequenced

can be used to study less amenable parasitic nematodes

blue print for human genome project

Why use C.elegans in parasite research?

cheap to maintain

don't have to use animals (as hosts)

easy to introduce DNA

knock out genes in days using RNAi

Potential new target for anti parasitic drugs:

Collagenous cuticle (highly layered and complex) - that all nematodes are encased in (specific structure)

- exoskeleton that must be shed/moulted to get to next larval stage

- synthesised 5 times during development (1st made in embryo)

- lots of steps involved in the production of collagen = degree of complexity (many enzymes involved) for the production of single collagen a worm)

- if not formed properly will be lethal, worms will not hatch from egg - if they do, very severely defected (look like a blob not

*complex - nematode specific process

* disrupt enzyme DPY-31 = collagen not processed and worms will fail to hatch from eggs

produce mutants in C.elegans for enzymes = get trapped in old cuticle, restricted by ring that is usually digested = worm will die

constricted in un-shed cuticle - Ecdysis defect

Summary:

Experimentally amenable model for parasitic nematode research

Genetics and transgenics can be applied to study gene function

Can rescue C. elegans mutants with parasite genes

Useful in defining drug resistance mechanism

and identifying new drug targets and new drug classes.