High Throughput Metagenomic Drug Screening in Mammalian Cells

DESCRIPTION (provided by applicant): In recent years there has been an increased interest in tapping the potential drug reservoir contained within the metagenome. To enable mammalian based screening of metagenomic libraries for novel drugs we have developed a method for bacterial delivery of natural products. We demonstrate with the anticancer drug violacein that bacterial delivery of natural products is simple and removes the need for trial and error based extract preparation. Preliminary work with microfluidic chips demonstrates the feasibility for high speed microdroplet formation using standard bacterial growth media. In Phase I we propose to extend this work by combining our bacterial drug delivery method with the power of microfluidic separation technology to carry out efficient, large-scale screening of the metagenome for novel natural products. It is expected that our technology will fulfill the unmet need for rapid discovery of new drugs to combat complex diseases such as cancer. PUBLIC HEALTH RELEVANCE: Approximately 22% of all deaths in the US are due to cancer, and it is estimated that by 2010 cancer will be responsible for more deaths worldwide than any other disease. Our novel method for screening the metagenome for bioactive molecules will allow us to add to the arsenal of natural products with potent anticancer activity. By utilizing bacteria as a source of drug production we will be assured of an almost limitless source of anticancer compound, avoiding a major bottleneck that would otherwise limit product availability to patients.