High-throughput identification of biologically active small molecules on Chlamydomonas
Simon E. Alfred and Corey Nislow
Dept. of Molecular Genetics, Univ. of Toronto, Toronto, Canada
Chlamydomonas reinhardtii, a single-celled eukaryotic photosynthetic green alga, is an effective model organism for understanding the cell-cycle, flagellar based motility, and photosynthesis and chloroplast biology. The recent completion of the Chlamydomonas genome provides strong genetic tractability in understanding Chlamydomonas biology, however, not all problems are well suited to genetic analysis; the challenges of lethality and genetic redundancy may limit the use of genetic techniques. A complementary approach to genetic methods is chemical biology. Chemical biology is the perturbation of biological systems with the use of small molecule probes. Advantages of this approach include modulation of effect by altering chemical concentration, time of application, and may overcome genetic redundancy to protein families. This work focuses on systematic screening of Chlamydomonas with a library of FDA approved and off market drugs to (i) determine the effects and targets of FDA drugs, and (ii) to develop small molecule research probes relevant to Chlamydomonas biology. Initial chemical screens with Chlamydomonas have proven effective. Findings from growth screens will be presented, as well as in depth detail on screening methodology and hit rate.
e-mail address of presenting author: simon.alfred@utoronto.ca