- Email: [email protected]
Proteins – an unfolding story
132
Forum
were detailed. In this section, the contents are accurate, up-to-date, and by avoiding much of the specialist terminology, written in a reader-friendly mode. In conclusion, anyone who requires a general awareness of the engineering and manufacturing for biotechnology in bioindustry will have reason to consult this book. Takeshi Omasa Dept of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita Osaka, 565-0871, Japan. e-mail: [email protected]
Protein drugs come of age Recombinant Protein Drugs (Milestones in Drug Therapy Series) Edited by Peter Buckel. Birkhäuser Verlag, 2001. 210 DM (x + 207 pages) ISBN 3 7643 5904 8
The biotechnology revolution of the past 30 years has had a profound impact on the direction of pharmaceutical research and development. Advances in molecular biology and immunology permitted the description of diseases at the molecular level and provided new paradigms for rational drug development. In addition, these developments provided us with the tools for manipulation of biological macromolecules, such as proteins and nucleic acids, and their large-scale production as a new generation of drugs. However, the translation of the knowledge from ‘bench to bedside’ would have been difficult without the close partnership of academic laboratories with pharmaceutical industries and the emergence of new ‘University spin off’ companies. Success of these endeavors is most evident in the significant number of currently approved recombinant protein drugs (>30) and in the growing list of therapeutic proteins awaiting regulatory approval (>300). Recombinant Protein Drugs celebrates these advances by offering a historical perspective on selected advances in protein drug discovery and development. The chapters are organized into four sections: (1) pioneers and business; (2) first generation protein drugs; (3) proteins with new functions: protein engineering; and (4) further improvement http://tibtech.trends.com
TRENDS in Biotechnology Vol.20 No.3 March 2002
of protein drugs. The first two chapters narrate the ‘pioneer stories’ of the development of recombinant interferons and hepatitis B vaccine. The excitement of the new beginnings is captured including the marriage of academia with industry, and the scientific challenges of the early days are also highlighted. The firstgeneration protein drugs are illustrated by three reviews on clotting factors, colony stimulating factors and tissue plasminogen activator. These reviews are comprehensive and cover basic sciences and clinical applications. The third section provides a glimpse of the current research on second-generation protein drugs with a review on immunokines (fusion proteins of cytokines with single-chain antibodies capable of binding tumor-associated antigens). The last section presents the challenges in protein drug delivery with discussions on two diverse approaches: protein formulation and gene delivery. Formulation of proteins in biodegradable polymers is a viable approach to enhance its stability and favor desirable pharmacokinetics. However, gene therapy approaches aimed at achieving expression of the therapeutic protein by the target cells present major hurdles that need to be overcome before they can be used in clinical applications. The book is well organized and well written. Its greatest strength as well as its unique feature is the historical perspectives presented by the pioneering scientists. It also provides an excellent sampling of currently approved therapeutic proteins and future challenges in protein drug development. Obviously this book is not meant to serve as a compendium on therapeutic proteins. In view of this, the topics of choice for the first two sections are justified. However, a broader coverage of current approaches in development of second-generation protein drugs and their delivery would have been more appropriate for the third and fourth sections. Despite this limitation, Recombinant Protein Drugs makes excellent reading for health professionals and biomedical researchers, especially for those interested in pharmaceutical biotechnology research. John Samuel Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada, T6G 2N8. e-mail: [email protected]
Proteins – an unfolding story From Protein Folding to New Enzymes Edited by Alan Berry and Sheena E. Radford. Portland Press, London, UK, 2001. £65.00 (156 pages) ISBN 1 85578 143 3
Protein folding and protein engineering are two vibrant areas of molecular biology and biophysics. The discovery of molecular chaperones that facilitate folding, the Nobel prize-winning prion hypothesis and the linking of protein misfolding with various diseases are just some of the recent exciting developments in these fields. Genome sequencing efforts have further stoked the furnaces that drive such research. This book touches on these and other areas. In April 2000, the Biochemical Society held its 68th symposium at the University of Leeds (Leeds, UK), an excellent conference by all accounts. The book takes its title from the symposium and its content from articles contributed by some of the speakers at the meeting. A review from Chris Dobson opens the book and a chapter on degradation of explosives by Neil Bruce concludes the book, as the editors put it, ‘with a bang’. In between are chapters on membrane proteins, prions, chaperones, molecular dynamics simulation, directed evolution, folding of helices and coiled coils. This wide-ranging book embraces several topics of intense current interest, with obvious relevance to the postgenomic era, important diseases and fundamental aspects of protein structure. Reflecting its origin, the book is a smorgasbord of contemporary molecular biology and biophysics, although some contributions have been more carefully prepared than others have. There are a few short chapters, a couple comprising a mere six pages of content between an abstract and some references. These rather thin sandwiches serve mainly as pointers to key references in the literature. Contributions to the book are pitched, primarily, to specialists, but the book is relatively readable and could certainly be recommended as a broad read to pique the interest of graduate students embarking on research in protein folding or protein engineering. However, it is not sufficiently substantial to challenge classics such as Creighton’s Protein Folding [1], which covered similar ground a decade ago but in greater depth.
Forum
The breadth of topics covered in the book is perhaps both a strength and a weakness. Many readers will find something of interest but might not want to read it cover to cover. The first chapter is an authoritative, albeit previously published, account of protein misfolding and the formation of amyloid structures, key processes in neurodegenerative diseases such as Alzheimer’s. In Chapter 2, Booth and colleagues describe the development of model lipid-bilayers for studying the folding of bacteriorhodopsin, probably the most heavily studied membrane protein. Serio and coworkers review their studies of a yeast prion protein in Chapter 3. This is followed by two chapters on chaperones. First, Naylor and Hartl discuss folding in the cytoplasm and the chaperone heat-shock protein of 70 kiloDaltons (Hsp70). Then Gierasch and colleagues describe the use of NMR to determine the structure of a fragment of Hsp70, called DnaK. Molecular dynamics simulation of protein unfolding is the focus of Chapter 6 by Daggett. In Chapter 7, Doig and coworkers review their studies of the kinetics of α-helix folding, work that has attracted some controversy. This chapter on helix formation and stability leads nicely into Chapter 8 by Woolfson and his group on the association of helices to form coiled-coils. This is work that develops the 40-year old ‘knobs into holes’ theory of Crick on the packing of helices. Directed evolution experiments aimed at enhancing the resistance of plants to nematodes are described by McPherson and Harrison in Chapter 9. Finally, Bruce and coworkers round off the book with their chapter on the degradation of explosives by nitrate ester reductases. From Protein Folding to New Enzymes is a partial record of an exciting symposium and a collection of interesting chapters. It is a well-presented monograph, although it is perhaps a shame that none of the figures is in colour. This cost-saving device has probably not reduced the price sufficiently for most impoverished PhD students. Other researchers might be more inclined to find and read articles in the scientific literature rather than dip into this book. More of a might-read than a must-read, nevertheless, the book is an interesting dispatch from the front-line of research into protein folding and design and will be a welcome addition to many institutional libraries. http://tibtech.trends.com
TRENDS in Biotechnology Vol.20 No.3 March 2002
Reference 1 Creighton, T.E., ed. (1992) Protein Folding, Freeman & Co, New York
Jonathan Hirst School of Chemistry, University of Nottingham, University Park, Nottingham, UK NG7 2RD. e-mail: [email protected]
Plant’s fingerprints Plant Genotyping. The DNA Fingerprinting of Plants Edited by Robert J. Henry, CABI Publishing, Wallingford, Oxon, UK, 2001. £55.00 (xiii + 325 pages) ISBN 0 85199515 2
This handsome hardcover book joined some other recent [1] and not-so recent [2] volumes on similar subject on my shelf. This volume covers a wide range of topics, including SSR, AFLP, RAPD/DAF and single nucleotide polymorphism (SNP) markers, genotyping technology and application of molecular markers to plant breeding. Such species as wheat, barley, sugarcane, forage species and even taro and tea tree (Maleleuca alternifolia) are covered, and germplasm resource analysis and marker data handling are also discussed. Several authors originate from Australia, which is not surprising in a book edited by Robert Henry – his lab at Southern Cross University has been very active in the area of molecular markers. This is not a lab manual, for that purpose the book edited by Caetano-Anolles and Gresshoff is a more appropriate choice [2]. However, the focus is on technology and much useful practical advice is given, with appropriate references. The article by Henry discusses parameters affecting DNA isolation from plant material. Several articles deal with SSR (microsatellite) markers and their application, with some overlap between them. For example, the article by Maguire discusses the production and use of SSR-enriched genomic libraries. This review could be even better if artifacts frequently encountered in such libraries, such as in vitro PCR-induced recombination between unrelated clones, were more thoroughly discussed. SNPs are becoming increasingly useful as genetic markers, taking advantage of rapid technology development associated with the Human Genome Project. It is therefore appropriate
133
that three articles are devoted to SNPs. Good, although brief reviews of SNP genotyping are provided – to serve as guides for further reading. I would welcome more discussion of the organization of high-throughput production genotyping in support of plant breeding in a commercial setting. Perhaps such information is not widely shared owing to the commercial concerns involved. However, the article by Lee and Henry briefly addresses some of the issues, including genotyping in support of plant breeders’ rights. Several articles would be useful for those interested in germplasm resources, and in managing seed banks. I especially enjoyed the discussion of marker analysis of tea tree accessions and correlations with chemical composition of oil. In comparison, the book edited by Phillips and Vasil [1] largely focuses on the construction of genetic maps and on reviewing genetic map construction in several species, complementing the present volume. Those interested in linkage mapping and physical mapping would find the book edited by Dear [3] very useful. A volume devoted to quantitative trait mapping is also available [4]. This book would be an excellent choice for those looking for an overview of the field, with relatively up-to date references (up to 2000) that serve as a guide to further reading. Plant breeders, or graduate students, especially those embarking on a molecular marker project would also find the book useful, even if not affordable, especially in conjunction with a lab manual. Given that the lifetime of similar publications tends to be short, because of rapid technical developments in the field, my suggestion would be to publish similar soft-cover volumes, at a lower price. J. Antoni Rafalski DuPont Crop Genetics, 1 Innovation Way, Newark, DE19711, USA. [email protected] References 1 Phillips, R.L. and Vasil, I.K., eds (2001) DNABased Markers in Plants, Kluver Academic Publishers 2 Caetano-Anolles, G. and Gresshoff, P.M., eds (1998) DNA Markers. Protocols, Applications and Overviews, Wiley-VCH 3 Dear, P.H., ed. (1997) Genome Mapping. A Practical Approach, IRL Press/Oxford University Press 4 Paterson, A.H., ed. (1998) Molecular Dissection of Complex Traits, CRC Press
Forum
were detailed. In this section, the contents are accurate, up-to-date, and by avoiding much of the specialist terminology, written in a reader-friendly mode. In conclusion, anyone who requires a general awareness of the engineering and manufacturing for biotechnology in bioindustry will have reason to consult this book. Takeshi Omasa Dept of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita Osaka, 565-0871, Japan. e-mail: [email protected]
Protein drugs come of age Recombinant Protein Drugs (Milestones in Drug Therapy Series) Edited by Peter Buckel. Birkhäuser Verlag, 2001. 210 DM (x + 207 pages) ISBN 3 7643 5904 8
The biotechnology revolution of the past 30 years has had a profound impact on the direction of pharmaceutical research and development. Advances in molecular biology and immunology permitted the description of diseases at the molecular level and provided new paradigms for rational drug development. In addition, these developments provided us with the tools for manipulation of biological macromolecules, such as proteins and nucleic acids, and their large-scale production as a new generation of drugs. However, the translation of the knowledge from ‘bench to bedside’ would have been difficult without the close partnership of academic laboratories with pharmaceutical industries and the emergence of new ‘University spin off’ companies. Success of these endeavors is most evident in the significant number of currently approved recombinant protein drugs (>30) and in the growing list of therapeutic proteins awaiting regulatory approval (>300). Recombinant Protein Drugs celebrates these advances by offering a historical perspective on selected advances in protein drug discovery and development. The chapters are organized into four sections: (1) pioneers and business; (2) first generation protein drugs; (3) proteins with new functions: protein engineering; and (4) further improvement http://tibtech.trends.com
TRENDS in Biotechnology Vol.20 No.3 March 2002
of protein drugs. The first two chapters narrate the ‘pioneer stories’ of the development of recombinant interferons and hepatitis B vaccine. The excitement of the new beginnings is captured including the marriage of academia with industry, and the scientific challenges of the early days are also highlighted. The firstgeneration protein drugs are illustrated by three reviews on clotting factors, colony stimulating factors and tissue plasminogen activator. These reviews are comprehensive and cover basic sciences and clinical applications. The third section provides a glimpse of the current research on second-generation protein drugs with a review on immunokines (fusion proteins of cytokines with single-chain antibodies capable of binding tumor-associated antigens). The last section presents the challenges in protein drug delivery with discussions on two diverse approaches: protein formulation and gene delivery. Formulation of proteins in biodegradable polymers is a viable approach to enhance its stability and favor desirable pharmacokinetics. However, gene therapy approaches aimed at achieving expression of the therapeutic protein by the target cells present major hurdles that need to be overcome before they can be used in clinical applications. The book is well organized and well written. Its greatest strength as well as its unique feature is the historical perspectives presented by the pioneering scientists. It also provides an excellent sampling of currently approved therapeutic proteins and future challenges in protein drug development. Obviously this book is not meant to serve as a compendium on therapeutic proteins. In view of this, the topics of choice for the first two sections are justified. However, a broader coverage of current approaches in development of second-generation protein drugs and their delivery would have been more appropriate for the third and fourth sections. Despite this limitation, Recombinant Protein Drugs makes excellent reading for health professionals and biomedical researchers, especially for those interested in pharmaceutical biotechnology research. John Samuel Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada, T6G 2N8. e-mail: [email protected]
Proteins – an unfolding story From Protein Folding to New Enzymes Edited by Alan Berry and Sheena E. Radford. Portland Press, London, UK, 2001. £65.00 (156 pages) ISBN 1 85578 143 3
Protein folding and protein engineering are two vibrant areas of molecular biology and biophysics. The discovery of molecular chaperones that facilitate folding, the Nobel prize-winning prion hypothesis and the linking of protein misfolding with various diseases are just some of the recent exciting developments in these fields. Genome sequencing efforts have further stoked the furnaces that drive such research. This book touches on these and other areas. In April 2000, the Biochemical Society held its 68th symposium at the University of Leeds (Leeds, UK), an excellent conference by all accounts. The book takes its title from the symposium and its content from articles contributed by some of the speakers at the meeting. A review from Chris Dobson opens the book and a chapter on degradation of explosives by Neil Bruce concludes the book, as the editors put it, ‘with a bang’. In between are chapters on membrane proteins, prions, chaperones, molecular dynamics simulation, directed evolution, folding of helices and coiled coils. This wide-ranging book embraces several topics of intense current interest, with obvious relevance to the postgenomic era, important diseases and fundamental aspects of protein structure. Reflecting its origin, the book is a smorgasbord of contemporary molecular biology and biophysics, although some contributions have been more carefully prepared than others have. There are a few short chapters, a couple comprising a mere six pages of content between an abstract and some references. These rather thin sandwiches serve mainly as pointers to key references in the literature. Contributions to the book are pitched, primarily, to specialists, but the book is relatively readable and could certainly be recommended as a broad read to pique the interest of graduate students embarking on research in protein folding or protein engineering. However, it is not sufficiently substantial to challenge classics such as Creighton’s Protein Folding [1], which covered similar ground a decade ago but in greater depth.
Forum
The breadth of topics covered in the book is perhaps both a strength and a weakness. Many readers will find something of interest but might not want to read it cover to cover. The first chapter is an authoritative, albeit previously published, account of protein misfolding and the formation of amyloid structures, key processes in neurodegenerative diseases such as Alzheimer’s. In Chapter 2, Booth and colleagues describe the development of model lipid-bilayers for studying the folding of bacteriorhodopsin, probably the most heavily studied membrane protein. Serio and coworkers review their studies of a yeast prion protein in Chapter 3. This is followed by two chapters on chaperones. First, Naylor and Hartl discuss folding in the cytoplasm and the chaperone heat-shock protein of 70 kiloDaltons (Hsp70). Then Gierasch and colleagues describe the use of NMR to determine the structure of a fragment of Hsp70, called DnaK. Molecular dynamics simulation of protein unfolding is the focus of Chapter 6 by Daggett. In Chapter 7, Doig and coworkers review their studies of the kinetics of α-helix folding, work that has attracted some controversy. This chapter on helix formation and stability leads nicely into Chapter 8 by Woolfson and his group on the association of helices to form coiled-coils. This is work that develops the 40-year old ‘knobs into holes’ theory of Crick on the packing of helices. Directed evolution experiments aimed at enhancing the resistance of plants to nematodes are described by McPherson and Harrison in Chapter 9. Finally, Bruce and coworkers round off the book with their chapter on the degradation of explosives by nitrate ester reductases. From Protein Folding to New Enzymes is a partial record of an exciting symposium and a collection of interesting chapters. It is a well-presented monograph, although it is perhaps a shame that none of the figures is in colour. This cost-saving device has probably not reduced the price sufficiently for most impoverished PhD students. Other researchers might be more inclined to find and read articles in the scientific literature rather than dip into this book. More of a might-read than a must-read, nevertheless, the book is an interesting dispatch from the front-line of research into protein folding and design and will be a welcome addition to many institutional libraries. http://tibtech.trends.com
TRENDS in Biotechnology Vol.20 No.3 March 2002
Reference 1 Creighton, T.E., ed. (1992) Protein Folding, Freeman & Co, New York
Jonathan Hirst School of Chemistry, University of Nottingham, University Park, Nottingham, UK NG7 2RD. e-mail: [email protected]
Plant’s fingerprints Plant Genotyping. The DNA Fingerprinting of Plants Edited by Robert J. Henry, CABI Publishing, Wallingford, Oxon, UK, 2001. £55.00 (xiii + 325 pages) ISBN 0 85199515 2
This handsome hardcover book joined some other recent [1] and not-so recent [2] volumes on similar subject on my shelf. This volume covers a wide range of topics, including SSR, AFLP, RAPD/DAF and single nucleotide polymorphism (SNP) markers, genotyping technology and application of molecular markers to plant breeding. Such species as wheat, barley, sugarcane, forage species and even taro and tea tree (Maleleuca alternifolia) are covered, and germplasm resource analysis and marker data handling are also discussed. Several authors originate from Australia, which is not surprising in a book edited by Robert Henry – his lab at Southern Cross University has been very active in the area of molecular markers. This is not a lab manual, for that purpose the book edited by Caetano-Anolles and Gresshoff is a more appropriate choice [2]. However, the focus is on technology and much useful practical advice is given, with appropriate references. The article by Henry discusses parameters affecting DNA isolation from plant material. Several articles deal with SSR (microsatellite) markers and their application, with some overlap between them. For example, the article by Maguire discusses the production and use of SSR-enriched genomic libraries. This review could be even better if artifacts frequently encountered in such libraries, such as in vitro PCR-induced recombination between unrelated clones, were more thoroughly discussed. SNPs are becoming increasingly useful as genetic markers, taking advantage of rapid technology development associated with the Human Genome Project. It is therefore appropriate
133
that three articles are devoted to SNPs. Good, although brief reviews of SNP genotyping are provided – to serve as guides for further reading. I would welcome more discussion of the organization of high-throughput production genotyping in support of plant breeding in a commercial setting. Perhaps such information is not widely shared owing to the commercial concerns involved. However, the article by Lee and Henry briefly addresses some of the issues, including genotyping in support of plant breeders’ rights. Several articles would be useful for those interested in germplasm resources, and in managing seed banks. I especially enjoyed the discussion of marker analysis of tea tree accessions and correlations with chemical composition of oil. In comparison, the book edited by Phillips and Vasil [1] largely focuses on the construction of genetic maps and on reviewing genetic map construction in several species, complementing the present volume. Those interested in linkage mapping and physical mapping would find the book edited by Dear [3] very useful. A volume devoted to quantitative trait mapping is also available [4]. This book would be an excellent choice for those looking for an overview of the field, with relatively up-to date references (up to 2000) that serve as a guide to further reading. Plant breeders, or graduate students, especially those embarking on a molecular marker project would also find the book useful, even if not affordable, especially in conjunction with a lab manual. Given that the lifetime of similar publications tends to be short, because of rapid technical developments in the field, my suggestion would be to publish similar soft-cover volumes, at a lower price. J. Antoni Rafalski DuPont Crop Genetics, 1 Innovation Way, Newark, DE19711, USA. [email protected] References 1 Phillips, R.L. and Vasil, I.K., eds (2001) DNABased Markers in Plants, Kluver Academic Publishers 2 Caetano-Anolles, G. and Gresshoff, P.M., eds (1998) DNA Markers. Protocols, Applications and Overviews, Wiley-VCH 3 Dear, P.H., ed. (1997) Genome Mapping. A Practical Approach, IRL Press/Oxford University Press 4 Paterson, A.H., ed. (1998) Molecular Dissection of Complex Traits, CRC Press