RESEARCH
Chemical Genetics
Chemical genetics represents an emerging powerful technology to aid scientists in elucidating biological systems with small-molecule compounds. In an attempt to find small molecules that arrest growth of malaria parasites, we have developed a fluorescence assay to screen against known and unknown targets. For instance, Telomerase Reverse Transcriptase is a known target which is responsive to retroviral reverse transcriptase inhibitors. We are targeting malarial telomerase reverse transcriptase protein with known HIV reverse transcriptase inhibitors to block telomerase activity. Additionally, We are collaborating with the Linnington lab at UCSC to screen for natural products as new anti-malarials. We have developed a simple method for detection of growth inhibition in malaria and it is sufficiently developed to screen large numbers of compounds. Additionally, we are elucidating the mode of action of ‘hits’ by identifying the target RNA or protein whose biological function had not been previously studied.
Small molecule screening strategy: Synchronized parasites (A) in multiwell plates (B) are treated with compounds from small molecule libraries using a pin transfer robot (C) and finally measured with a fluorescence plate reader (D). Right panel showing similar attributes on glass slides for small molecule microarray. (Courtesy, www.jidonline.org)