A comprehensive guide to the revolutionary area of systems biology and its application in cell culture engineering, this volume presents an overall picture of the current topics central to structural and functional genomics, proteomics, metabolomics and bioinformatics, including such hot topics as RNAi, metabolic engineering and unfolded protein response. It includes reviews of the cellular response of environmental modulation such as low temperature and osmolarity, critical assessments of the applications of metablomics and fluxomics approaches, examination of the utility of modulation of key genes and a presentation of a theory of chemical organisation which provides new view on the system's structure. The clearly written chapters by experts in the field describe methods applicable to investigating the unique facets of cell culture.

The suppression of apoptosis by the IGF system is critical for normal cell development, proliferation, differentiation and motility. Aberrations in IGF signalling mechanisms contribute to cell transformation, tumour progression and metastasis. Many questions remain to be answered as to how exactly the IGF system mediates its effects both in normal and tumour cells and how the IGF-1R interacting proteins and downstream signalling cascades are regulated. The importance of the IGF system is underscored by the significant interest in the development of anti-IGF therapies for IGF sensitive cancers. Future developments in cancer therapy are likely to focus on methods to target these therapies to diseased but not normal cells. 14. Acknowledgements We would like to thank Kurt Tidmore for preparing the illustrations. The Health Research Board of Ireland and Science Foundation Ireland are grateful acknowledged for funding. 15. References Adamo M., Roberts C. T., Jr. and LeRoith D. (1992) How distinct are the insulin and insul- like growth factor I signalling systems? Biofactors 3, 151-7. Adams T. E., Epa V. C., Garrett T. P. and Ward C. W. (2000) Structure and function of the type 1 insulin-like growth factor receptor. Cell Mol Life Sci 57, 1050-93. Adler V., Polotskaya A., Wagner F. and Kraft A. S. (1992) Affinity-purified c-Jun ami- terminal protein kinase requires serine/threonine phosphorylation for activity. J Biol Chem 267, 17001-5.

The completion of the Human Genome Project and the rapid progress in cell bi- ogy and biochemical engineering, are major forces driving the steady increase of approved biotech products, especially biopharmaceuticals, in the market. Today mammalian cell products ("products from cells"), primarily monoclonals, cytokines, recombinant glycoproteins, and, increasingly, vaccines, dominate the biopharmaceutical industry. Moreover, a small number of products consisting of in vitro cultivated cells ("cells as product") for regenerative medicine have also been introduced in the market. Their efficient production requires comprehensive knowledge of biological as well as biochemical mammalian cell culture fundamentals (e.g., cell characteristics and metabolism, cell line establishment, culture medium optimization) and related engineering principles (e.g., bioreactor design, process scale-up and optimization). In addition, new developments focusing on cell line development, animal-free c- ture media, disposables and the implications of changing processes (multi-purpo- facilities) have to be taken into account. While a number of excellent books treating the basic methods and applications of mammalian cell culture technology have been published, only little attention has been afforded to their engineering aspects. The aim of this book is to make a contribution to closing this gap; it particularly focuses on the interactions between biological and biochemical and engineering principles in processes derived from cell cultures. It is not intended to give a c- prehensive overview of the literature. This has been done extensively elsewhere.

The rapid expansion of synthetic biology is due to the design and construction of synthetic gene networks that have opened many new avenues in fundamental and applied research. Synthetic Gene Networks: Methods and Protocols provides the necessary information to design and construct synthetic gene networks in different host backgrounds. Divided into four convenient sections, this volume focuses on design concepts to devise synthetic gene networks and how mathematical models can be applied to the predictable engineering of desired network features. The volume continues by highlighting the construction and validation of biologic tools, describing strategies to optimize and streamline the host cell for optimized network performance, and covering how optimally designed gene networks can be implemented in a large variety of host cells ranging from bacteria over yeast and insect cells to plant and mammalian cell culture. Written in the successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Synthetic Gene Networks: Methods and Protocols serves as an invaluable resource for established biologists, engineers, and computer scientists or novices just entering into the rapidly growing field of synthetic biology

A comprehensive guide to the revolutionary area of systems biology and its application in cell culture engineering, this volume presents an overall picture of the current topics central to structural and functional genomics, proteomics, metabolomics and bioinformatics, including such hot topics as RNAi, metabolic engineering and unfolded protein response. It includes reviews of the cellular response of environmental modulation such as low temperature and osmolarity, critical assessments of the applications of metabolomics and fluxomics approaches, examination of the utility of modulation of key genes and a presentation of a theory of chemical organisation which provides a new view of the system's structure. The clearly written chapters by experts in the field describe methods applicable to investigating the unique facets of cell culture. The book should be of interest to all those working in cell culture development and drug discovery in pharmaceutical and biotechnology companies as well as in academic institutions. It provides an invaluable resource for students and researchers in biotechnology, cell culture, genomics and bioinformatics.

The suppression of apoptosis by the IGF system is critical for normal cell development, proliferation, differentiation and motility. Aberrations in IGF signalling mechanisms contribute to cell transformation, tumour progression and metastasis. Many questions remain to be answered as to how exactly the IGF system mediates its effects both in normal and tumour cells and how the IGF-1R interacting proteins and downstream signalling cascades are regulated. The importance of the IGF system is underscored by the significant interest in the development of anti-IGF therapies for IGF sensitive cancers. Future developments in cancer therapy are likely to focus on methods to target these therapies to diseased but not normal cells. 14. Acknowledgements We would like to thank Kurt Tidmore for preparing the illustrations. The Health Research Board of Ireland and Science Foundation Ireland are grateful acknowledged for funding. 15. References Adamo M., Roberts C. T., Jr. and LeRoith D. (1992) How distinct are the insulin and insul- like growth factor I signalling systems? Biofactors 3, 151-7. Adams T. E., Epa V. C., Garrett T. P. and Ward C. W. (2000) Structure and function of the type 1 insulin-like growth factor receptor. Cell Mol Life Sci 57, 1050-93. Adler V., Polotskaya A., Wagner F. and Kraft A. S. (1992) Affinity-purified c-Jun ami- terminal protein kinase requires serine/threonine phosphorylation for activity. J Biol Chem 267, 17001-5.

The rapid expansion of synthetic biology is due to the design and construction of synthetic gene networks that have opened many new avenues in fundamental and applied research. Synthetic Gene Networks: Methods and Protocols provides the necessary information to design and construct synthetic gene networks in different host backgrounds. Divided into four convenient sections, this volume focuses on design concepts to devise synthetic gene networks and how mathematical models can be applied to the predictable engineering of desired network features. The volume continues by highlighting the construction and validation of biologic tools, describing strategies to optimize and streamline the host cell for optimized network performance, and covering how optimally designed gene networks can be implemented in a large variety of host cells ranging from bacteria over yeast and insect cells to plant and mammalian cell culture. Written in the successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Synthetic Gene Networks: Methods and Protocols serves as an invaluable resource for established biologists, engineers, and computer scientists or novices just entering into the rapidly growing field of synthetic biology

The completion of the Human Genome Project and the rapid progress in cell bi- ogy and biochemical engineering, are major forces driving the steady increase of approved biotech products, especially biopharmaceuticals, in the market. Today mammalian cell products ("products from cells"), primarily monoclonals, cytokines, recombinant glycoproteins, and, increasingly, vaccines, dominate the biopharmaceutical industry. Moreover, a small number of products consisting of in vitro cultivated cells ("cells as product") for regenerative medicine have also been introduced in the market. Their efficient production requires comprehensive knowledge of biological as well as biochemical mammalian cell culture fundamentals (e.g., cell characteristics and metabolism, cell line establishment, culture medium optimization) and related engineering principles (e.g., bioreactor design, process scale-up and optimization). In addition, new developments focusing on cell line development, animal-free c- ture media, disposables and the implications of changing processes (multi-purpo- facilities) have to be taken into account. While a number of excellent books treating the basic methods and applications of mammalian cell culture technology have been published, only little attention has been afforded to their engineering aspects. The aim of this book is to make a contribution to closing this gap; it particularly focuses on the interactions between biological and biochemical and engineering principles in processes derived from cell cultures. It is not intended to give a c- prehensive overview of the literature. This has been done extensively elsewhere.