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Chemical Genetics (chemical + genetics)
Selected AbstractsNew technologies for chemical geneticsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S37 2001Leslie A. Walling Abstract Chemical genetics, in which small molecules are used in lieu of mutations to study biological processes, requires large and diverse chemical libraries to specifically perturb different biological pathways. Here we describe a suite of technologies that enable chemical libraries prepared by split-pool solid phase synthesis to be screened in a diverse range of chemical genetic assays. Compounds are synthesized on 500 micron high-capacity polystyrene beads, and arrayed into individual wells of 384-well plates using a hand-held bead arrayer. Compounds are cleaved from synthesis beads using a chemically-resistant ceramic dispensing system, producing individual stock solutions of single compounds. Nanoliter volumes of these solutions are then transferred into assay plates using an array of stainless steel pins mounted on a robotic arm. We have designed reusable 1536- and 6144-well assay plates made of silicone rubber that can be cast in the laboratory and filled by hand. This integrated technology platform enables hundreds of biological assays to be performed from the product of a single synthesis bead, enabling the results of different chemical genetic experiments to be directly compared. J. Cell. Biochem. Suppl. 37: 7,12, 2001. © 2002 Wiley-Liss, Inc. [source] Chemical genetics: catalysing pathway exploration and new target discoveryJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 11 2007Joshua I Armstrong Abstract Chemical genetics couples the availability of diverse chemistry with the strengths of molecular genetics to dissect signalling pathways in complex organisms. Plant biology laboratories have integrated this approach into their repertoire for probing hormone signalling, physiology and pesticide mode of action. These studies have led to the discovery of compounds that regulate development and the response to environmental stress. Chemical genetics facilitates our understanding of genetic signalling pathways and offers a new approach to pest management and plant health by enabling the direct chemical modulation of plant defence signalling. Copyright © 2007 Society of Chemical Industry [source] Orthogonal Chemical Genetic Approaches for Unraveling Signaling PathwaysIUBMB LIFE, Issue 6 2005Kavita Shah Abstract While chemical genetic approach uses small molecules to probe protein functions in cells or organisms, orthogonal chemical genetics refers to strategies that utilize reengineered protein-small molecule interfaces, to alter specificities, in order to probe their functions. The advantage of orthogonal chemical genetics is that the changes at the interfaces are generally so minute that it goes undetected by natural processes, and thus depicts a true physiological picture of biological phenomenon. This review highlights the recent advances in the area of orthogonal chemical genetics, especially those designed to probe signaling processes. Dynamic protein-protein and enzyme-substrate interactions following stimuli form the foundation of signal transduction. These processes not only break spatial and temporal boundaries between interacting proteins, but also impart distinct regulatory properties by creating functional diversity at the interfaces. Functional and temporal modulation of these dynamic interactions by specific chemical probes provides extremely powerful tools to initiate, ablate, decouple and deconvolute different components of a signaling pathway at multiple stages. Not surprisingly, multiple receptor-ligand reengineering approaches have been developed in the last decade to selectively manipulate these transient interactions with the aim of unraveling signaling events. However, given the diversity of protein-protein interactions and novel chemical genetic probes developed to perturb these processes, a short review cannot do adequate justice to all aspects of signaling. For this reason, this review focuses on some orthogonal chemical-genetic strategies that are developed to study signaling processes involving enzyme-substrate interactions. IUBMB Life, 57: 397-405, 2005 [source] New technologies for chemical geneticsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S37 2001Leslie A. Walling Abstract Chemical genetics, in which small molecules are used in lieu of mutations to study biological processes, requires large and diverse chemical libraries to specifically perturb different biological pathways. Here we describe a suite of technologies that enable chemical libraries prepared by split-pool solid phase synthesis to be screened in a diverse range of chemical genetic assays. Compounds are synthesized on 500 micron high-capacity polystyrene beads, and arrayed into individual wells of 384-well plates using a hand-held bead arrayer. Compounds are cleaved from synthesis beads using a chemically-resistant ceramic dispensing system, producing individual stock solutions of single compounds. Nanoliter volumes of these solutions are then transferred into assay plates using an array of stainless steel pins mounted on a robotic arm. We have designed reusable 1536- and 6144-well assay plates made of silicone rubber that can be cast in the laboratory and filled by hand. This integrated technology platform enables hundreds of biological assays to be performed from the product of a single synthesis bead, enabling the results of different chemical genetic experiments to be directly compared. J. Cell. Biochem. Suppl. 37: 7,12, 2001. © 2002 Wiley-Liss, Inc. [source] The emerging field of chemical genetics: potential applications for pesticide discoveryPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 12 2007Terence A Walsh Abstract The use of small molecules to probe biological systems, generally described as ,chemical genetics', has grown considerably in the past 7 years, especially in areas related to human biology and therapeutics. This review describes some aspects of chemical genetics technologies that can be usefully applied to pesticide target discovery and lead generation. The chemical genetics approach (consisting of a phenotype screen, a chemical library and a robust target identification methodology) is compared with conventional and target-based screening. The outcomes of a chemical genetics approach are novel protein targets coupled with in vivo -active chemical ligands. The ,chemistry-first' paradigm of the chemical genetics approach can circumvent some of the obstacles that have emerged for the exploitation of novel but chemically unvalidated targets identified from genetic or genomic screens. Some of the advantages and challenges in using chemical genetics approaches are reviewed. Copyright © 2007 Society of Chemical Industry [source] | |||||||||||||