Grant: Operating Grant

Although we have a number of new tools to identify genes that might play a role in Schizophrenia, however, this has not helped us to understand thsi disorder. There are several reasons for this: one is that we do not know the function of some of the genes, another is that so much data has been generated that it is not easy to understand what it all means. An analogy would be having a large jigsaw puzzle with many small pieces, and no picture to help to understand how the pieces fit together. In this research we propose using a model organism, the nematode Caenorhabditis elegans, with a small easily studied nervous system that can be studied much more rapidly than a mammal could be studied. We will focus on a simple behavior that is altered in Schizophrenia. This behavior is habituation, perhaps the simplest form of learning that is seen in all animals studied. Habituation is learning to ignore stimuli that do not predict anything good or bad- thus can safely be ignored. C. elegans shares a number of genes with humans (similar genes in different organisms are called homologues), and so our plan is use databases of genes implicated in human neurological disorders to study the role of their homologues in habituation in C. elegans. We will use a new high-throughput behaviour analysis method to test habituation for all of the C. elegans genes homologous to genes implicated in Schizophrenia. Using data from these descriptions we will discover how the genes work together in gene pathways. Our hypothesis is that by understanding the role of gene networks in habituation in C. elegans we will shed light on how they contribute to a disorder and may lead to new ways to diagnose and treat this disorder.