Grant: Operating Grant

We propose to continue our CIHR-funded work to identify new potential drugs for two human diseases. Towards this end, we use the tiny nematode worm, C. elegans, as a model system because it is easy to do experiments with and because more than 70% of its proteins are similar to those of humans. Hence, most of the discoveries we make can ultimately be exploited to better understand human biology and cure diseases. With our CIHR funds, we screened ~70,000 small drug-like molecules for their ability to induce defects in C. elegans and identified 634 active molecules. Through additional screens, we found that 73 of these molecules can also kill parasitic nematodes, but have minimal effects on other types of animals in our preliminary screens. Given that one third of the world is infected with a parasitic nematode, these novel molecules will be pursued as potential anti-parasitic drugs. We also found another 22 molecules that not only disrupt C. elegans, but also modulate heart development of fish. Previous work has demonstrated the therapeutic potential of small molecule modulators of fish heart activity for treating human heart malfunction. Upon renewing our CIHR grant, we will continue to characterize the ability of these potential drugs to kill parasitic worms and ameliorate heart conditions. We will further exploit the worm to identify the protein target of the most interesting of these 95 molecules. At the very least, this project will yield over 20 new small molecule tools with defined protein targets that will enable future scientific discoveries. However, we are optimistic that we can develop many of our compounds into new drug leads to combat parasitic nematodes and heart disease for the benefit of all humans.