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Functional Genomic Approaches Targeting the Wnt Signaling Network

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The sequencing of whole genomes, including those of model organisms, has provided an unprecedented resource to the research community to make sense of the genetic code. However, it is the advent of novel functional genomic technologies that have been truly instrumental in bridging the gap between gene sequence and gene function. The past few years have witnessed a rapid growth in the development and implementation of high-throughput screening (HTS) technologies that researchers are now using to discover “gene-function” in an unbiased, systematic, time and costefficient manner. One of the most promising functional genomic approach that has emerged in the past few years is based on RNA-interference (RNAi) in which the introduction of double-stranded RNA (dsRNA) or short-interfering RNA (siRNA) into cells or whole organisms can effectively suppress endogenous gene expression. The RNAi-based screening technology has made it feasible to query the function of whole genomes in the regulation of conserved cell-signaling pathways and the crosstalk between them in “signaling networks” that are known to influence important cell biological functions, such as cell proliferation and growth, cell morphology, cell adhesion and cell death. In this review we discuss the application, advantages and limitations of RNAi and other post-genomic technologies in the identification of novel modulators of cell-signaling pathways, with a focus on the Wnt signaling pathway. We also discuss the future scope and utility of designing additional variants of these genome-scale screens.

Keywords: HTS; RNAi; Wnt; network; signaling; wingless

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/138945009788680455

Publication date: July 1, 2009

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  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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