生物信息学技术

High content screening (HCS) plays an important role in target selection in primary and secondary screening, but further developments in informatics and data management are needed for strategic implementation of HCS in the drug discovery process. An organization charter for the Rese ...

The complexity of human biology requires a systems approach that uses computational approaches to integrate different data types. Systems biology encompasses the complete biological system of metabolic and signaling pathways, which can be assessed by measuring global gene expr ...

Visualization is essential to the understanding of complex data derived from high content screening. It is necessary to present information in a way that captures patterns and trends in the data in order to answer specific questions while also providing a way to formulate new questions and hyp ...

Cancers result from large-scale deregulation of genes that lead to cancer pathophysiologies such as increase proliferation, decreased apoptosis, increased motility, increased angiogenesis, and others. Genes that influence proliferation and apoptosis are particularly ...

In most pharmaceutical and biotechnology companies there is a need to always improve the quality of lead candidates. This demand resulted in the use of cell-based screening as a method of choice in drug discovery (1,2). High content screening (HCS) is multiplexed, functional cell-based scree ...

The process of target validation identifies and assesses whether a molecular target merits the development of pharmaceuticals for therapeutic application. The most valuable application of high content screening to target validation is at the early stages of the process when genet ...

Dynamic protein phosphorylation, a major cellular regulatory system, is tightly controlled by coordinating the reversible action of protein kinases and phosphatases. Recent evidence is consistent with sophisticated mechanisms that regulate both kinases and phosphatas ...

This chapter describes the design and development of cell-based assays, in which quantitation of the intracellular translocation of a target protein—rather than binding or catalytic activity—provides the primary assay readout. These are inherently high content assays, and they p ...

The most frequent reason cited for withdrawal of an approved drug is toxicity, yet no simple solution exists to adequately predict such adverse effects. Compound prioritization and optimization during in vitro screening cascades need to be based on confidence, not only in efficacy and bio ...

Retinal ganglion cells (RGC) are the projection neurons of the eye. The RGC is the primary cell type injured in a variety of diseases of the optic nerve, including glaucoma and optic neuritis. The most well-established extrinsic signal of RGC survival and axonal outgrowth is the neurotrophin bra ...

This chapter summarizes the roles of nanomaterials in biomedical applications, focusing on those highlighted in this volume. A brief history of nanoscience and technology and a general introduction to the field are presented. Then, the chemical and physical properties of nanostruct ...

Nano/microparticulate drug delivery systems with homogeneous size distribution and predefined shape are important in understanding the influence of the geometry and dimensions of these systems on blood circulation times and cellular uptake. We present a general method using wa ...

The protocols herein describe colony-lift and fluorescent immunoassays that were used to identify bacterial colonies that produced single-chain fragment variable (ScFv) recombinant antibodies reactive with zero-state silver. A large (approx 2.9-billion member) phage-d ...

Nanoparticles have been extensively investigated in drug-delivery systems. Especially, the effectiveness of the surface-functionalized nanoparticles, which consist of copolymers with functional molecules, is well demonstrated. This chapter describes the complete ...

We have developed methods for nanostructure fabrication relying on the size and shape of a polynucleotide to dictate the overall structure of an assemblage of individual semiconductor nanoparticles. Use of the circular plasmids pUCLeu4 and φχ 174 when anchored to a suitably derivatiz ...

Structural DNA nanotechnology uses unusual DNA motifs to build target shapes and arrangements. These unusual motifs are generated by reciprocal exchange of DNA backbones, leading to branched systems with many strands and multiple helical domains. The motifs may be combined by sticky- ...

A significant challenge in bionanotechnology is the discovery of effective biological interfaces that allow inorganic nanoscale materials to mimic effectively their biological counterparts. Much like de novo design of proteins, the rational design of such interfaces is a daunt ...

A technique for simultaneously measuring changes in extracellular glucose, lactate, and oxygen concentrations in conjunction with acidification rates on a Cytosensor™ Microphysiometer is described. Platinum electrodes are inserted into the standard Cytosensor plunger ...

Arrays of vertically aligned carbon nanofibers (VACNFs) provide structures that are well suited for the direct integration and manipulation of molecular-scale phenomena within intact, live cells. VACNFs are fabricated via a combination of microfabrication techniques and cat ...

Semiconductor nanoparticles, also known as quantum dots, are receiving increasing attention for their biological applications. These nanomaterials are photoluminescent and are being developed both as dyes and as sensors. Here we describe our “sensor” use of quantum dots to detect d ...