637
Proteomics Clin. Appl. 2014, 8, 637–639
Editorial Animal models for translational proteomics Experimentation and observation of animal biology is fundamental for our understanding of human biology, health and disease. Documented history of animal models date back to Aristotle (382–322 BC) and Galen (130–200 AC) who dissected and compared the anatomy of animals like horse, pig, goat and marine species, to deduce knowledge about human biology. Since then, important milestones in our understanding of human physiology and cell biology were achieved through studies of a very wide variety of animal models, including the famous experiments of Galvani, (1780ies) Pasteur (1880ies) and Pavlov (1890ies). Genetic dissections of simple organisms like Saccharomyces cereviciae, as well as inbred strains of small animal models like Drosophila, C. elegans, and rodents are fundamental to our knowledge about human genetics, and also the first decades of protein research relied mainly on purification and characterization of non-human proteins, which could be readily obtained in the large quantities needed before the days of protein mass spectrometry (MS). With the advance of 2Dgels and MS methods, large scale studies of human proteins became approachable, and the past 2 decades have seen an avalanche of human proteome studies, both those aiming to map the protein parts-lists of human tissues and body fluids, and those aiming to explore biomarkers with clinical relevance. 2014 is the year when the first (almost) complete maps of the human proteome were presented [1, 2]. 93%, or 18248 of the 19629 predicted human proteins have now been documented by MS, and our tools and knowledge for investigating the dynamics of the human proteome has been greatly enhanced by important data repositories like Nextprot (http://www.nextprot.org), PeptideAtlas (http://www.peptideatlas.org), SRM atlas (http://www.srmatlas.org) and Human Protein Atlas (http://www.proteinatlas.org) that provide access to information about proteins, isoforms and their abundance in most human tissues and body fluids and cell types. Despite this massive progress in human proteomics, a parallel progress in clinical applications have come at a disappointingly slow pace, and it is very clear that achieving clinical advances still depends heavily on our studies of informative animal models. This is particularly true for research where progress in clinical proteomics is hampered by entire lack of access to sampling relevant and live human tissues, which is the case for e.g. all neurological disorders. A renaissance for animal models is also sparked by the current progress in metagenomics research. Our growing understanding of the importance of commensal bacteria on human health and for clinical applications [3] has also made it quite clear that understanding the new level of complexity that lies in the interactions of human and bacterial genomes, and with environmental factors (nutrition, lifestyle and medication) requires access to translational model organisms that can be perturbed and studied in large scale experiments. In comparison to the human proteome field, advances and tools for non-human proteomics has lagged behind, and the lack of genome and proteome data of non-human species has limited the selection of available models to a few classic model organism species. This outlook is now rapidly changing, partly due to the high speed and low cost of genome sequencing, and also due to rising awareness that classic model organisms like mouse and flies are often inadequate for studying human biology, which is particularly true for neurological, metabolic, and immunological diseases [4]. This thematic issue is dedicated to update progress on proteome research in classical models like mouse, rat, drosophila and C. elegans, and to introduce some of the novel model organisms, which are newcomers to biomedical research. Two reviews are dedicated to cover progress in animal models applicable to the two major clinical challenges in the western world, namely cancer and cardiovascular diseases. In “Application of proteomics in the study of rodent models of cancer”, Terp and Ditzel present an overview of rodent models used for cancer research, and discuss proteomics strategies for improving diagnostics, prognosis and for preclinical C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Emøke Bendixen
www.clinical.proteomics-journal.com
638
Proteomics Clin. Appl. 2014, 8, 637–639
testing of cancer therapies. A major advantage of mouse models is the availability genetically engineered models, and also well developed procedures for introducing human xenografts, which provides access to wide range of humanized mouse cancer models. The use of these models in biomarker research and for preclinical testing is discussed. In “Sizing up models of heart failure: Proteomics from flies to humans”, Kooij et al. presents a comparative overview of the variety of animal models that are available for modeling human cardiovascular disorders. This review discusses shortcomings and advantages of using dog, pig, rat, mouse, Drosophila and zebrafish. Moreover, the importance of protein phosphorylation, and of major kinase signaling pathways in heart disease is being discussed, and a cross-species comparison of kinase signaling pathways and their relevance for heart disease is presented. As the human metagenomics research is currently changing our understanding of causality and treatment of a wide range of human diseases, it also highligths the need for novel animal models which can be perturbed and studied in large scales, to untangle the mindblowingly complex interactions of human and bacterial genetics with environmental factors (nutrition, lifestyle and medication). This is the topic covered by Cassidy and Tholey in “Model organisms proteomics as tool for the study of host-microbiome interactions”. This review provides an overview of recent progress in developing model organisms, which are uniquely suited for investigating the role of commensal bacterial communities on human health. Farm animals represent a novel and very interesting resource for biomedical and clinical proteomics. These species have a dual relevance to human health, as they are both a major source for food as well as being a resource as biomedical models organism. Moreover, understanding biology and production traits of farm animals is increasingly relevant for economy, food safety and animal welfare with the increase of globalization and industrialization of food production. The increasing demand on food production, agricultural methods and environmental challenges makes farm animal research one of the fastest growing field in applied biology. Four reviews are dedicated to explore relevance and progress of farm animal proteomics. In “Proteomics in farm animals models of human diseases”, Ceciliani et al. provides a panoramic overview of farm animal models, which are already well established for proteome research. These authors discuss in details the special relevance of using pig and cow for studies of host pathogen interaction, as these species, due to their close interactions to humans, shares many human pathogens. Their review also explains the dual gain in biomedical as well as agricultural production associated with exploring farm animal proteomes. In “The chicken model of spontaneous ovarian cancer”, Hawkridge presents the relevance and advantages of using chicken models for studying human ovarian cancer. Chicken develop a much higher rate (10–35%) of spontaneous ovarian cancers than both humans and rodent models, and the controlled genetic background of line-bred chicken together with a short ovulation cycles (24 hours) makes them highly applicable for translational studies of onset and progression of human ovarian cancers. Pig has a special status as a novel and upcoming model organism. Despite its large size (comparable to man), which makes it far from handy in most laboratory settings, the genetic and physiological similarities between pig and man, presents this species as one of the most promising model for human clinical applications. The fact that pig, like man, and, unlike most other mammals, is an omnivore, make pigs particularly relevant models for nutrigenomic research. This is the topic of “Intestinal proteomics in pig models of necrotising enterocolitis, short bowel syndrome and intra-uterine growth restriction” by Jiang and Sangild. These authors are among the pioneers in developing pig models for studying intestinal dysfunction of neonatal human infants. Their review describes the use of pig models for studying gut development in neonatal and premature infants, with particular focus on understanding some of the major health threats to pre-mature and neonatal infants, namely inflammatory gut syndromes, like necrotizing enterocolitis (NEC) and short bowel syndrome (SBS). Finally, Bassols et al. presents a broad overview on the stautus of “The pig as an animal model for human pathologies: A proteomics perspective”. Their review focus on relevant pig models for diabetes, metabolic disorders, obesity, immunology as well as neurological disorders. Examples are presented on porcine models carrying gene variants that are well known to cause neurological disorders in man. These porcine models are of large value as progress in knowledge and treatment of human neuropathies is still greatly hampered by lack of relevant translational models. Moreover, these authors also discus the relevance of pig as the most likely and suited donor for xenotransplantation of organs and cells to humans.
C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.clinical.proteomics-journal.com
639
Proteomics Clin. Appl. 2014, 8, 637–639
With this selection of reviews we hope to reflect some of the current progress in developing novel translational animal models, and most importantly we hope to communicate the value of widening the selection of model organisms. Studying the proteomes of novel model organisms make them increasingly available for translational research, and relevant animal models are more than ever needed for translating our massive knowledge of proteomes into clinical applications.
Emøke Bendixen
References [1] Wilhelm, M., Schlegl, J., Hahne, H., Moghaddas Gholami, A. et al., Mass-spectrometry-based draft of the human proteome. Nature, 2014, 509, 582–587. [2] Kim, M. S., Pinto, S. M., Getnet, D., Nirujogi, R. S. et al., A draft map of the human proteome. Nature, 2014, 509, 575–581. [3] Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R. et.al., Host-gut microbiota metabolic interactions. Science, 2012, 336, 1262–1267. [4] van der Worp, H. B., Howells, D. W., Sena, E. S., Porritt, M. J. et al., Can animal models of disease reliably inform human studies? PLoS Med., 2010, 7, e1000245. doi: 10.1371/journal.pmed.1000245.
C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.clinical.proteomics-journal.com
Proteomics Clin. Appl. 2014, 8, 637–639
Editorial Animal models for translational proteomics Experimentation and observation of animal biology is fundamental for our understanding of human biology, health and disease. Documented history of animal models date back to Aristotle (382–322 BC) and Galen (130–200 AC) who dissected and compared the anatomy of animals like horse, pig, goat and marine species, to deduce knowledge about human biology. Since then, important milestones in our understanding of human physiology and cell biology were achieved through studies of a very wide variety of animal models, including the famous experiments of Galvani, (1780ies) Pasteur (1880ies) and Pavlov (1890ies). Genetic dissections of simple organisms like Saccharomyces cereviciae, as well as inbred strains of small animal models like Drosophila, C. elegans, and rodents are fundamental to our knowledge about human genetics, and also the first decades of protein research relied mainly on purification and characterization of non-human proteins, which could be readily obtained in the large quantities needed before the days of protein mass spectrometry (MS). With the advance of 2Dgels and MS methods, large scale studies of human proteins became approachable, and the past 2 decades have seen an avalanche of human proteome studies, both those aiming to map the protein parts-lists of human tissues and body fluids, and those aiming to explore biomarkers with clinical relevance. 2014 is the year when the first (almost) complete maps of the human proteome were presented [1, 2]. 93%, or 18248 of the 19629 predicted human proteins have now been documented by MS, and our tools and knowledge for investigating the dynamics of the human proteome has been greatly enhanced by important data repositories like Nextprot (http://www.nextprot.org), PeptideAtlas (http://www.peptideatlas.org), SRM atlas (http://www.srmatlas.org) and Human Protein Atlas (http://www.proteinatlas.org) that provide access to information about proteins, isoforms and their abundance in most human tissues and body fluids and cell types. Despite this massive progress in human proteomics, a parallel progress in clinical applications have come at a disappointingly slow pace, and it is very clear that achieving clinical advances still depends heavily on our studies of informative animal models. This is particularly true for research where progress in clinical proteomics is hampered by entire lack of access to sampling relevant and live human tissues, which is the case for e.g. all neurological disorders. A renaissance for animal models is also sparked by the current progress in metagenomics research. Our growing understanding of the importance of commensal bacteria on human health and for clinical applications [3] has also made it quite clear that understanding the new level of complexity that lies in the interactions of human and bacterial genomes, and with environmental factors (nutrition, lifestyle and medication) requires access to translational model organisms that can be perturbed and studied in large scale experiments. In comparison to the human proteome field, advances and tools for non-human proteomics has lagged behind, and the lack of genome and proteome data of non-human species has limited the selection of available models to a few classic model organism species. This outlook is now rapidly changing, partly due to the high speed and low cost of genome sequencing, and also due to rising awareness that classic model organisms like mouse and flies are often inadequate for studying human biology, which is particularly true for neurological, metabolic, and immunological diseases [4]. This thematic issue is dedicated to update progress on proteome research in classical models like mouse, rat, drosophila and C. elegans, and to introduce some of the novel model organisms, which are newcomers to biomedical research. Two reviews are dedicated to cover progress in animal models applicable to the two major clinical challenges in the western world, namely cancer and cardiovascular diseases. In “Application of proteomics in the study of rodent models of cancer”, Terp and Ditzel present an overview of rodent models used for cancer research, and discuss proteomics strategies for improving diagnostics, prognosis and for preclinical C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Emøke Bendixen
www.clinical.proteomics-journal.com
638
Proteomics Clin. Appl. 2014, 8, 637–639
testing of cancer therapies. A major advantage of mouse models is the availability genetically engineered models, and also well developed procedures for introducing human xenografts, which provides access to wide range of humanized mouse cancer models. The use of these models in biomarker research and for preclinical testing is discussed. In “Sizing up models of heart failure: Proteomics from flies to humans”, Kooij et al. presents a comparative overview of the variety of animal models that are available for modeling human cardiovascular disorders. This review discusses shortcomings and advantages of using dog, pig, rat, mouse, Drosophila and zebrafish. Moreover, the importance of protein phosphorylation, and of major kinase signaling pathways in heart disease is being discussed, and a cross-species comparison of kinase signaling pathways and their relevance for heart disease is presented. As the human metagenomics research is currently changing our understanding of causality and treatment of a wide range of human diseases, it also highligths the need for novel animal models which can be perturbed and studied in large scales, to untangle the mindblowingly complex interactions of human and bacterial genetics with environmental factors (nutrition, lifestyle and medication). This is the topic covered by Cassidy and Tholey in “Model organisms proteomics as tool for the study of host-microbiome interactions”. This review provides an overview of recent progress in developing model organisms, which are uniquely suited for investigating the role of commensal bacterial communities on human health. Farm animals represent a novel and very interesting resource for biomedical and clinical proteomics. These species have a dual relevance to human health, as they are both a major source for food as well as being a resource as biomedical models organism. Moreover, understanding biology and production traits of farm animals is increasingly relevant for economy, food safety and animal welfare with the increase of globalization and industrialization of food production. The increasing demand on food production, agricultural methods and environmental challenges makes farm animal research one of the fastest growing field in applied biology. Four reviews are dedicated to explore relevance and progress of farm animal proteomics. In “Proteomics in farm animals models of human diseases”, Ceciliani et al. provides a panoramic overview of farm animal models, which are already well established for proteome research. These authors discuss in details the special relevance of using pig and cow for studies of host pathogen interaction, as these species, due to their close interactions to humans, shares many human pathogens. Their review also explains the dual gain in biomedical as well as agricultural production associated with exploring farm animal proteomes. In “The chicken model of spontaneous ovarian cancer”, Hawkridge presents the relevance and advantages of using chicken models for studying human ovarian cancer. Chicken develop a much higher rate (10–35%) of spontaneous ovarian cancers than both humans and rodent models, and the controlled genetic background of line-bred chicken together with a short ovulation cycles (24 hours) makes them highly applicable for translational studies of onset and progression of human ovarian cancers. Pig has a special status as a novel and upcoming model organism. Despite its large size (comparable to man), which makes it far from handy in most laboratory settings, the genetic and physiological similarities between pig and man, presents this species as one of the most promising model for human clinical applications. The fact that pig, like man, and, unlike most other mammals, is an omnivore, make pigs particularly relevant models for nutrigenomic research. This is the topic of “Intestinal proteomics in pig models of necrotising enterocolitis, short bowel syndrome and intra-uterine growth restriction” by Jiang and Sangild. These authors are among the pioneers in developing pig models for studying intestinal dysfunction of neonatal human infants. Their review describes the use of pig models for studying gut development in neonatal and premature infants, with particular focus on understanding some of the major health threats to pre-mature and neonatal infants, namely inflammatory gut syndromes, like necrotizing enterocolitis (NEC) and short bowel syndrome (SBS). Finally, Bassols et al. presents a broad overview on the stautus of “The pig as an animal model for human pathologies: A proteomics perspective”. Their review focus on relevant pig models for diabetes, metabolic disorders, obesity, immunology as well as neurological disorders. Examples are presented on porcine models carrying gene variants that are well known to cause neurological disorders in man. These porcine models are of large value as progress in knowledge and treatment of human neuropathies is still greatly hampered by lack of relevant translational models. Moreover, these authors also discus the relevance of pig as the most likely and suited donor for xenotransplantation of organs and cells to humans.
C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.clinical.proteomics-journal.com
639
Proteomics Clin. Appl. 2014, 8, 637–639
With this selection of reviews we hope to reflect some of the current progress in developing novel translational animal models, and most importantly we hope to communicate the value of widening the selection of model organisms. Studying the proteomes of novel model organisms make them increasingly available for translational research, and relevant animal models are more than ever needed for translating our massive knowledge of proteomes into clinical applications.
Emøke Bendixen
References [1] Wilhelm, M., Schlegl, J., Hahne, H., Moghaddas Gholami, A. et al., Mass-spectrometry-based draft of the human proteome. Nature, 2014, 509, 582–587. [2] Kim, M. S., Pinto, S. M., Getnet, D., Nirujogi, R. S. et al., A draft map of the human proteome. Nature, 2014, 509, 575–581. [3] Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R. et.al., Host-gut microbiota metabolic interactions. Science, 2012, 336, 1262–1267. [4] van der Worp, H. B., Howells, D. W., Sena, E. S., Porritt, M. J. et al., Can animal models of disease reliably inform human studies? PLoS Med., 2010, 7, e1000245. doi: 10.1371/journal.pmed.1000245.
C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.clinical.proteomics-journal.com
