MONOCLONAL ANTIBODIES TO NEURAL ANTIGENS IN ASCARIS

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The aim of this project is to devise immunohistochemical labels for neurons and synapses in the motornervous system of the large parasitic nematode Ascaris. We will generate monoclonal antibodies against subsets of neurons, against synapses and against enzymes known to be important in neuronal function, e.g. choline acetyltransferase, the biosynthetic enzyme for acetylcholine. Since we have electrophysiological and anatomical information about many of the neurons in the motor nervous system, we can correlate the presence of specific antigens with known physiological activities. Our long-term objective is to generate a series of labels so that the function of a neuron can be determined using histochemical techniques that label the molecules that mediate function. This will enable us to determine the functional anatomy of the entire nematode nervous system in the detail that will be required before we can test our understanding of the cellular and molecular mechanisms that the nervous system uses to process information. Gaining a basic understanding of the Ascaris nervous system is important since Ascaris is a model nematode in which to investigate the control of locomotion in nematodes. The Ascaris motor nervous system is anatomically similar to that of other nematodes, so it is reasonable to assume that this similarity will also apply at the functional level. By studying the mechanisms underlying the activity of the neuromuscular system of Ascaris, general principles applying to other nematodes will be found. This basic understanding of the nematode nervous system will make a contribution to parasite biology, and allow differences in the biology between host and parasite to be identified as targets for anthelmintic drugs. In view of the agricultural impact of nematodes on food supplies, and the problems they cause as animal and human parasites, especially in tropical and economically less-developed countries, this is an important health-related goal.