| Chemical genetics is the study of biology using small molecules, rather than mutations, to modulate cellular protein function. We developed a new general method to regulate protein function using a combination of synthetic organic chemistry and chemical genetic selection of receptor proteins. In addition, we extended existing methods to study signal transduction using small molecules that induce dimerization of proteins, particularly those that produce a gain-of-function phenotype.; We developed a new method in solid-phase organic synthesis toward the production of libraries of small molecule dimerizers. We also developed assay methods designed specifically to discover novel small molecule dimerizers. With these advances, we achieved our goal of developing a general program to discover novel small molecule activators of protein function.; Systematic chemical genetics aims to annotate every member of a compound collection with rich datasets delimiting its biological performance. We developed a platform to facilitate the delivery of compounds resulting from solid-phase, diversity-oriented synthesis into both phenotypic and proteomic assays. This one-bead, multiple stock-solution approach is central to a platform for discovery in chemical genetics. |
