Artmann / Chien Bioengineering in Cell and Tissue Research

1. Auflage 2008
ISBN: 978-3-540-75409-1
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 693 Seiten, eBook

The idea of publishing this book on “Bioengineering in Cell and Tissue Research” was originated by Gerhard M. Artmann, with the goal of writing about our dreams and making the reader dream with the authors and be fascinated. The book is meant to have life and spirit, and to become a pioneer in technology and sciences, es- cially the life science. The chapters in this book are written by excellent scientists on advanced, frontier technology and address scienti?c questions that need consid- able thinking in terms of engineering. The aims are to provide the readers, including students, faculty, and all scientists working in academia and industry, new infor- tion on bioengineering in cell and tissue research to enhance their understanding and innovation. This book is composed of six sections that cover a broad hierarchy from genes to the universe. These sections are Genes, Genome and Information Network; Cell and Tissue Imaging; Regenerative Medicine and Nanoengineering; Mechanics of Soft Tissues, Fluids and Molecules; Bioengineering in Clinical Applications; and Plant and Microbial Bioengineering.

Zielgruppe

Research

Autoren/Hrsg.

Artmann, Gerhard M.

Chien, Shu

Inhaltsverzeichnis

Genes, Genome and Information Network.- Reporter Genes in Cell Based ultra High Throughput Screening.- Gene Arrays for Gene Discovery.- Physical Modulation of Cellular Information Networks.- Cell and Tissue Imaging.- Fluorescence Live-Cell Imaging: Principles and Applications in Mechanobiology.- Optical Coherence Tomography (OCT) – An Emerging Technology for Three-Dimensional Imaging of Biological Tissues.- Ultrasonic Strain Imaging and Reconstructive Elastography for Biological Tissue.- Regenerative Medicine and Nanoengineering.- Aspects of Embryonic Stem Cell Derived Somatic Cell Therapy of Degenerative Diseases.- Collagen Fabrication for the Cell-based Implants in Regenerative Medicine.- Tissue Engineering – Combining Cells and Biomaterials into Functional Tissues.- Micro and Nano Patterning for Cell and Tissue Engineering.- Integrative Nanobioengineering: Novel Bioelectronic Tools for Real Time Pharmaceutical High Content Screening in Living Cells and Tissues.- Mechanics of Soft Tissues, Fluids and Molecules.- Soft Materials in Technology and Biology – Characteristics, Properties, and Parameter Identification.- Modeling Cellular Adaptation to Mechanical Stress.- How Strong is the Beating of Cardiac Myocytes? – The Cell Drum Solution.- Mechanical Homeostasis of Cardiovascular Tissue.- The Role of Macromolecules in Stabilization and De-Stabilization of Biofluids.- Hemoglobin Senses Body Temperature.- Bioengineering in Clinical Applications.- Nitric Oxide in the Vascular System: Meet a Challenge.- Vascular Endothelial Responses to Disturbed Flow: Pathologic Implications for Atherosclerosis.- Why is Sepsis an Ongoing Clinical Challenge? Lipopolysaccharide Effects on Red Blood Cell Volume.- Bioengineering of Inflammation and Cell Activation: Autodigestion inShock.- Percutaneous Vertebroplasty: A Review of Two Intraoperative Complications.- Plant and Microbial Bioengineering.- Molecular Crowding: A Way to Deal with Crowding in Photosynthetic Membranes.- Higher Plants as Bioreactors. Gene Technology with C3-Type Plants to Optimize CO2 Fixation for Production of Biomass and Bio-Energy.- Controlling Microbial Adhesion: A Surface Engineering Approach.- Air Purification Technology by Means of Cluster Ions Generated by Plasma Discharge at Atmospheric Pressure.- Astrobiology.

Leseproben

Chapter 1 Reporter Genes in Cell Based ultra High Throughput Screening (p. 3-4)

Stefan Golz

Bayer Healthcare AG, Institute for Target Research, 42096Wuppertal, Germany, [e-mail]

Abstract Pharma research in most organizations is organized in discrete phases together building a "value chain" along which discovery programs process to fi- nally drug candidates for clinical testing. The process envisioned to identify targetspecific modulators lacking several side effects. Following a technical assessment of the targets "drugability", the probability to identify small molecule modulators, and technical feasibility target-specific assays are developed to probe the corporate compound collection for meanful leads. "High-Throughput-Screening" (HTS) started roughly one decade ago with the introduction of laboratory automation to handle the different assay steps typically performed in microtiter plates. Today a large arsenal of screening technologies is available for researchers in industry and academia to set up uHTS or HTS assays. Here the use of reporter genes offer an alternative for following signal transduction pathways from receptors at the cell surface to nuclear gene transcription in living cells.

1.1 Introduction

The modern drug research process has reversed the classical pharmacological strategy. Today, research programs are initiated based on biological evidence suggesting a particular gene or gene product to be a meaningful target for small molecule drugs useful for therapies. The process envisioned to identify target-specific modulators lacking several side effects. Also, it allows setting up a linear drug discovery process starting from target identification to finally delivering molecules for clinical development. One central element is lead discovery through high-throughput screening of comprehensive corporate compound collections. Pharma research in most organizations is organized in discrete phases together building a "value chain" along which discovery programs process to finally drug candidated for clinical testing (Hüser et al. 2006).

This pipeline is fueled by targets suggested from external or in-house generated data suggesting a gene or gene product to be disease relevant. Today a large arsenal of technologies is available for researchers in industry and academia to generate data in support of a functional link between a given gene and a disease state.

1.2 From Gene to Target

Following a technical assessment of the targets "drugability" (Hopkins and Groom, 2002), the probability to identify small molecule modulators, and technical feasibility target-specific assays are developed to probe the corporate compound collection for meanful leads. Lead discovery in the pharmaceutical industry today still depends largely on experimental screening of compound collections. To this end, the industry has invested heavily in expanding their compound files and established appropiate screening capabilities to handle large numbers of compounds within a reasonable period of time. "High-Troughput-Screening" (HTS) started roughly one decade ago with the introduction of laboratory automation to handle the different assay steps typically performed in microtiter plates. HTS technologies during the last decade have witnessed remarkable developments. Assay technologies have advanced to provide a large variety of various cell-based and biochemical test formats for a large spectrum of disease relevant target classes (Walters and Namchuk, 2003). In parallel, further miniaturization of assays volumes and parallelization of processing have further increased the test throughput. The ultra-high-throughput is required to fully exploit big compound files of >,1million compounds and is performed entirely in 1536-well plates with assay volumes between 5 – 10 ìl. This assay carrier together with fully-automated robotic systems allow for testing in excess of 200,000 compounds per day. The comprehensive substance collection, together with sophisticated screening technologies, have resulted in a clear advantages in lead discovery especially for poorly druggable targets with a poor track record in the past.