Chemical-genetic modifier screens

Fig. 6-6 Chemical-genetic modifier screens, (a) By putting cells in a defined cell state, it is possible to identify small-molecule suppressors and enhancers, (b) Examples of data collected from a screen for chemical-genetic modifiers using a growth assay in budding yeast (data from Harvard University, MCB100 Experimental Biology course). Each row corresponds to a...

Fig. 6-9 Target identification of a suppressor of rapamycin [42]. (a) SMIR4 a suppressor of rapamycin identified using a chemical-genetic modifier screen, (b) Identification of gene products that interact with biotin-SMIR4 using a yeast protein microarray [42].

K.M. Koeller, S.J. Haggarty, B.D. Perkins, I. Leykin, J.C. Wong, M.C. Kao, S.L. Schreiber, Chemical genetic modifier screens small molecule trichostatin suppressors as probes of intracellular histone and tubulin acetylation, Chem. Biol. 2003, 10, 397-410. 

Most recently, we reported small molecule arrays on photoaffinity crosslinker coated gold surfaces (17). The small molecule arrays were fabricated by photoreaction, and then analyzed by SPR imaging technique. The small molecules don t have to be modified chemically for immobilization. The small molecules, which can interact with a target protein, can be screened by this methodology. Therefore, the integration of photoaffinity small molecule array and SPR imaging technique can be the first step of reverse chemical genetics. 

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