DOCSLIB.ORG

Systems Biology Success Stories In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Systems Biology Success Stories In SUCCESS STORIES IN SYSTEMS BIOLOGY Project funded by the European Comission under the Seventh Framework Programme for Research and Technological Development Contents Welcome 2 Research 3 A model that gets to the heart of systems biology 3 Denis Noble, Oxford University Taking a systems-eye view of cancers in children 5 Walter Kolch, Systems Biology Ireland Systems biology study points to Turing model of finger formation 7 James Sharpe, Centre for Genomic Regulation Balancing flavour and texture in tomatoes - with systems biology 9 Stuart Dunbar, Syngenta Systems X.ch: Swiss bank on systems biology 11 Daniel Vonder Muehll, SystemsX, Gisou van der Goot, EPF Lausanne, Cris Kuhlemeier, University of Bern Answering big questions with a small bug 13 Luis Serrano, Centre for Genomic Regulation Blueprints for life 15 Bas Teusink, Netherlands Platform for Systems Biology Merrimack: Following a systems path to drug discovery 17 Peter Sorger, Massachusetts Institute of Technology, and Birgit Schoeberl, Merrimack Pharmaceuticals Beating the conundrum of variability in cardiac simulations 19 Blanca Rodriguez, Oxford University Stats and modelling – a Belgian diagnostic tool for arthritis 21 Thibault Helleputte, DNAlytics Virtual Liver Network: a collaborative solution to hepatic diseases 23 Adriano Henney, Virtual Liver Network Tools and Resources 25 SBML: A lingua franca for systems biology 25 Michael Hucka, California Institute of Technology Model Support: JWS Online and BioModels Database 27 Jacky Snoep, Stellenbosch University, and Henning Hermjakob, European Bioinformatics Institute SYSMic: An interdisciplinary skills course for biologists 29 Gerold Baier and Geraint Thomas, University College London COPASI: An open source software package easing the path to modelling 31 Pedro Mendes, University of Manchester SEEK and ye shall find data 33 Katy Wolstencroft, University of Leiden 1 ISBE - www.isbe.eu Welcome I am very pleased to introduce this collection of success stories in systems biology, produced as part of the Infrastructure for Systems Biology Europe (ISBE) project and funded through the European Union Seventh Framework Programme. This is just a small sample of the cutting edge BIOGRAPHY research being carried out in systems biology in academic, clinical and industrial settings which is making an increasingly significant impact as we seek to tackle grand societal challenges in areas as diverse as health, agriculture and biotechnology. In the past fifteen years, systems biology research has become embedded across a range of biological and biomedical fields. This has been driven by the growing abundance and complexity of large biological data sets, the development of tools and techniques with which to perform comprehensive, genome-wide analyses, and the capacity to share these via high speed connections between disparate research groups and disciplines. Using a systems approach, life scientists are now able, for the first time, to study the complex and dynamic interplay between the components RIChaRd KITnEY IS of a system (be it at the level of a cell, tissue, organ, organism or population). This can now go PROfESSOR Of BIOMEdICaL beyond understanding function, to enable intervention in the behaviour of the system in a predictive SYSTEMS EnGInEERInG, ChaIRMan Of ThE InSTITuTE and rational manner. The stories told in this publication illustrate the breadth of work going on in Of SYSTEMS and SYnThETIC this dynamic area. BIOLOGY and CO-dIRECTOR Of ThE EPSRC naTIOnaL Challenges remain, however: how to increase access to modelling, developing workable standards CEnTRE fOR SYnThETIC BIOLOGY and InnOvaTIOn aT that enable the effective reuse of data and models as well as training new generations of scientists IMPERIaL COLLEGE LOndOn. in this multidisciplinary approach. A number of the tools and resources featured in this collection have been developed to address individual bottlenecks but an integrated infrastructure for systems Kitney is a leading researcher in biology is needed if we are truly to exploit the potential of systems biology. From 2012-2015, the the field of synthetic biology and, with Professor Paul ISBE consortium of 23 partners from 11 EU member states has been working with the academic, Freemont, has been clinical and industrial research communities to develop plans for a systems biology infrastructure responsible for developing the that will address these challenges with services that support a range of users, from novices to UK National Centre for Synthetic Biology - which is experts, from SMEs to Big Pharma, from university labs to hospital clinics. Our proposals for the now recognised as one of the infrastructure’s development over the coming years have been published in a business plan (July leading international centres in 2015) and the roll out of preliminary services is due to commence in late 2015. the field. In June 2001, Professor Kitney I would like to thank my colleagues from academia and industry who gave up their time for this was awarded the Order of the collection. They have given a fascinating insight into the iterative research process that is the basis British Empire (OBE) in the Queen's Birthday Honours List of systems biology, the cycle of experimentation and computational modelling that harnesses the for services to Information potential of ‘big data’ and turns it into tangible outcomes for society. Technology in Healthcare. Yours Prof. Richard I Kitney, OBE FREng Coordinator, Infrastructure for Systems Biology Europe Imperial College London ISBE - www.isbe.eu 2 BIOGRAPHY PROF. DENIS NOBLE DISCUSSES THE DEVELOPMENT OF HIS WORK IN CARDIAC CELL MODELLING FROM 1960 TO THE PRESENT Your heart: without it, you wouldn’t survive formulae and spent late nights punching in very long. So medicine strives to keep it healthy machine code in his allotted time between 2 and fix it if something goes wrong. Yet the and 4am. heart’s central role in our bodies can also make it difficult to test out new clinical approaches in Soon his work paid off and the heart model humans. One way to get around this is to build began to work. “It didn’t take too long to get to DENIS NOBLE IS A BRITISH a mathematical model that predicts how the the point where rhythm was coming out of the BIOLOGIST WHO WAS THE heart will behave, and today the ‘virtual heart’ equations,” recalls Prof. Noble, who is today an FIRST TO MODEL CARDIAC CELLS, DETAILED IN TWO approach is helping to make drug discovery and Emeritus Professor at Oxford University and PAPERS IN NATURE IN 1960. HE testing safer. President of the International Union of WAS EDUCATED AT UNIVERSITY Physiological Sciences. Papers in the COLLEGE LONDON AND MOVED prestigious journal Nature followed swiftly, and TO OXFORD IN 1963 AS Middle out means that you since then the heart model and experimental FELLOW AND TUTOR IN data have closely intertwined, building up our PHYSIOLOGY AT BALLIOL start at one level - which might COLLEGE. FROM 1984 TO 2004, be in the middle, in our case it’s knowledge of how this key organ works. HE HELD THE BURDON the cell. Then you reach down SANDERSON CHAIR OF to individual molecules and you In some cases, the model has informed the CARDIOVASCULAR PHYSIOLOGY reach up to the organ. experiments - Noble recalls how in the early AT OXFORD UNIVERSITY. 1960s his model put paid to a method of using He is now Professor Emeritus double probes to stimulate heart tissue in the and co-Director of lab: the maths clearly showed that the Computational Physiology. His The heart model has its origins in 1960, and its experimental approach was disrupting heart research focuses on using growth since then exemplifies the systems cell function. In other cases, experimental computer models of biological biology approach of using modelling and findings enhanced the model. “By about 1967, organs and organ systems to interpret function from the experimental data to enable new insights. It the existence of calcium channels had been molecular level to the whole began when Denis Noble and his PhD demonstrated, and that was the first point at organism. supervisor Otto Hutter worked with heart which it was obvious that the model would tissue at University College London. They were have to be expanded,” says Prof. Noble. “That interested in a type of electrical ‘gate’ in heart process of expanding and taking more and cells called the potassium channel, and Noble more into account has gone on ever since.” wanted to develop a mathematical model of the heart to explore its actions. In the decades since he punched machine code into the Mercury, Prof. Noble has worked with He based his work on a 1952 mathematical collaborators around the world to build up the model that described the characteristics of heart model and shed new light on how ion excitable cells, and to build up the model Noble channels work. Meanwhile, computer managed to wrangle some time on the Ferranti technology grew too, enabling more Mercury Computer in London. He sat in on sophisticated modelling and the development maths lectures to get up to speed with the of a virtual organ. The growth of the heart 3 ISBE - www.isbe.eu model exemplifies the ‘middle-out’ approach He now sees potential for the virtual heart to that Prof. Noble has long supported. “Middle continue informing drug discovery and out means that you start at one level - which regulation, thereby reducing risks in drug CuRREnT might be in the middle, in our case it’s the cell,” development. “Many side effects of drugs hit dEvELOPMEnTS he explains. “Then you reach down to individual the heart and cause arrhythmia, that has in the In CaRdIaC CELL molecules and you reach up to the organ.” past been the cause of withdrawal of drugs,” MOdELLInG he says. “And many of the companies have got out of this kind of work, it’s too risky so we are Premature heartbeats explained We used computation to show looking to see if you can use the model to filter as a change in the stability at an early stage synergistic actions of properties of the dynamical why ranolazine’s combination system of the heart cell during potential drugs.
Load more

Recommended publications
  • COMPLEX SYSTEMS BIOLOGY and HEGEL's PHILOSOPHY Kazuyuki
    COMPLEX SYSTEMS BIOLOGY AND HEGEL’S PHILOSOPHY Kazuyuki Ikko Takahashi KandaSurugadai 1-1, Chiyoda, Tokyo 101-8301, Meiji University ABSTRACT In this study I will argue that Hegel’s philosophy has similarity to the self- organization theories of Prigogine and Kauffman and complex systems biology of Kaneko, and is therefore an idea in advance of its times. In The Philosophy of Nature, Hegel’s interest is in how nature evolves through the mechanism of self-organization. He was writing before Darwin proposed the theory of evolution, and his dialectic is aimed at analyzing and describing development in the logical sense. The important feature of this work is their analysis of the fundamental structures by which order is generated. Hegel struggled to produce the concept of life from that of matter. He proposed that matter should develop into organism, but only in a logical sense. Nature itself is a system of producing spontaneous order through the random motion of the contingent. Then Hegel tackles living things. He would like to say that the basis of life is the non-equilibrium self-referential structure. In more modern terminology, we could interpret this as meaning that the first organism emerged from interaction between high polymers. Living creatures exhibit flexibility and plasticity through fluctuations in these elements. Complex systems biology uses a dynamical systems approach to explain how living things acquire diversity, stability and spontaneity. First, simple single-celled organisms arose through interactions between proteins and nucleic acids. These are the archae-bacteria in modern terminology. Next, the development of eukaryote cells from the prokaryotes is explained by symbiogenesis or endosymbiotic theory.
    [Show full text]
  • Chemical Genomics 33
    Curr. Issues Mol. Biol. (2002) 4: 33-43. Chemical Genomics 33 Chemical Genomics: A Systematic Approach in Biological Research and Drug Discovery X.F. Steven Zheng1* and Ting-Fung Chan2 synthesis (Russell and Eggleston 2000) and new screening technologies such as small chemical compound (MacBeath 1Department of Pathology and Immunology and 2Molecular et al. 1999) and protein microarrays (MacBeath and and Cellular Biology Program, Campus Box 8069 Schreiber 2000; Zhu et al. 2000; Haab et al. 2001). In this Washington University School of Medicine article, we will provide a detailed analysis of the current 660 South Euclid Avenue, St. Louis, Missouri 63110 USA state of chemical genomics and its potential impact on biological and medical research, and pharmaceutical development. Abstract Chemical Biology or Genetics The knowledge of complete sequences of different organisms is dramatically changing the landscape of Since the seminal study of pea genetics by Mendal in 1865, biological research and pharmaceutical development. genetic analysis has been the benchmark for understanding We are experiencing a transition from a trial-and-error gene or protein functions. In classical genetics or forward approach in traditional biological research and natural genetics, the genomic DNA of a model organism or cell is product drug discovery to a systematic operation in randomly mutagenized to generate large numbers of genomics and target-specific drug design and mutants, which are screened for a desirable phenotype or selection. Small, cell-permeable and target-specific trait, such as alteration in growth, appearance or behavior. chemical ligands are particularly useful in systematic The phenotypes are then used to identify the responsible genomic approaches to study biological questions.
    [Show full text]
  • Identification and Dynamics of the Human ZDHHC16-ZDHHC6 Palmitoylation Cascade
    RESEARCH ARTICLE Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade Laurence Abrami1†, Tiziano Dallavilla1,2†, Patrick A Sandoz1, Mustafa Demir1, Be´ atrice Kunz1, Georgios Savoglidis2, Vassily Hatzimanikatis2*, F Gisou van der Goot1* 1Global Health Institute, Faculty of Life Sciences, Ecole Polytechnique Fe´de´rale de Lausanne, Lausanne, Switzerland; 2Laboratory of Computational Systems Biotechnology, Faculty of Basic Sciences, Ecole Polytechnique Fe´de´rale de Lausanne, Lausanne, Switzerland Abstract S-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC palmitoyltransferase family is still limited. Here we show that human ZDHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, ZDHHC16, revealing the first palmitoylation cascade. The combination of site specific mutagenesis of the three ZDHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the eight differentially palmitoylated ZDHHC6 species. We found that species rapidly interconvert through the action of ZDHHC16 and the Acyl Protein Thioesterase APT2, that each species varies in terms of turnover rate and activity, altogether allowing the cell to robustly *For correspondence: tune its ZDHHC6 activity. [email protected] DOI: https://doi.org/10.7554/eLife.27826.001 (VH); [email protected] (FGG) †These authors contributed equally to this work Introduction Cells constantly interact with and respond to their environment. This requires tight control of protein Competing interests: The function in time and in space, which largely occurs through reversible post-translational modifica- authors declare that no tions of proteins, such as phosphorylation, ubiquitination and S-palmitoylation.
    [Show full text]
  • Pore Formation: an Ancient Yet Complex Form of Attack ⁎ Ioan Iacovache, F
    Available online at www.sciencedirect.com Biochimica et Biophysica Acta 1778 (2008) 1611–1623 www.elsevier.com/locate/bbamem Review Pore formation: An ancient yet complex form of attack ⁎ Ioan Iacovache, F. Gisou van der Goot , Lucile Pernot Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Faculty of Life Sciences, Station 15, CH 1015 Lausanne, Switzerland Received 13 November 2007; received in revised form 3 January 2008; accepted 4 January 2008 Available online 12 February 2008 Abstract Bacteria, as well as higher organisms such as sea anemones or earthworms, have developed sophisticated virulence factors such as the pore- forming toxins (PFTs) to mount their attack against the host. One of the most fascinating aspects of PFTs is that they can adopt a water-soluble form at the beginning of their lifetime and become an integral transmembrane protein in the membrane of the target cells. There is a growing understanding of the sequence of events and the various conformational changes undergone by these toxins in order to bind to the host cell surface, to penetrate the cell membranes and to achieve pore formation. These points will be addressed in this review. © 2008 Elsevier B.V. All rights reserved. Keywords: Pore-forming toxin; Perforin; Cholesterol-dependent cytolysin; Aerolysin; Actinoporin Contents 1. Introduction..............................................................1611 2. Structural classification of pore-forming toxins............................................1612 2.1. α-PFT .............................................................1612 2.1.1. Colicins........................................................1612 2.1.2. Actinoporins .....................................................1612 2.1.3. Insecticidal pore-forming toxins of the Cry family..................................1615 2.2. The ß-PFTs ..........................................................1615 2.2.1. S. aureus PFTs....................................................1615 2.2.2.
    [Show full text]
  • Complex Systems Analysis of Arrested Neural Cell Differentiation During Development and Analogous Cell Cycling Models in Carcinogenesis
    [04-01-2012 Preprint Update] Complex Systems Analysis of Arrested Neural Cell Differentiation during Development and Analogous Cell Cycling Models in Carcinogenesis V. I. Prisecaru and I.C. Baianu AFC-NMR & NIR Microspectroscopy Facility, College of ACES, FSHN & NPRE Departments, University of Illinois at Urbana, Urbana, IL. 61801, USA Email address: ibaianu @illinois.edu 1.Introduction A new approach to the modular, complex systems analysis of nonlinear dynamics of arrested neural cell Differentiation--induced cell proliferation during organismic development and the analogous cell cycling network transformations involved in carcinogenesis is proposed. Neural tissue arrested differentiation that induces cell proliferation during perturbed development and Carcinogenesis are complex processes that involve dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments. Such 'dynamically inter-connected' biomolecules form numerous inter- related pathways referred to as 'molecular networks'. One such family of signaling pathways contains Nature Precedings : hdl:10101/npre.2012.7101.2 Posted 2 Apr 2012 the cell cyclins. Cyclins are proteins that link several critical pro-apoptotic and other cell cycling/division components, including the tumor suppressor gene TP53 and its product, the Thomsen-Friedenreich antigen (T antigen), Rb, mdm2, c-Myc, p21, p27, Bax, Bad and Bcl-2, which play major roles in various neoplastic transformations of many tissues. 1. Arrested Cell Differentiation in Neural
    [Show full text]
  • Link Mining for Kernel-Based Compound-Protein Interaction Predictions Using a Chemogenomics Approach
    Link Mining for Kernel-based Compound-Protein Interaction Predictions Using a Chemogenomics Approach Masahito Ohue1,2,3,4*, Takuro Yamazaki3, Tomohiro Ban4, and Yutaka Akiyama1,2,3,4* 1Department of Computer Science, School of Computing, Tokyo Institute of Technology, Japan 2Advanced Computational Drug Discovery Unit, Institute of Innovative Research, Tokyo Institute of Technology, Japan 3Department of Computer Science, Faculty of Engineering, Tokyo Institute of Technology, Japan 4Department of Computer Science, Graduate School of Information Science and Engineering, Tokyo Institute of Technology, Japan *[email protected], [email protected] Abstract. Virtual screening (VS) is widely used during computational drug dis- covery to reduce costs. Chemogenomics-based virtual screening (CGBVS) can be used to predict new compound-protein interactions (CPIs) from known CPI network data using several methods, including machine learning and data min- ing. Although CGBVS facilitates highly efficient and accurate CPI prediction, it has poor performance for prediction of new compounds for which CPIs are un- known. The pairwise kernel method (PKM) is a state-of-the-art CGBVS method and shows high accuracy for prediction of new compounds. In this study, on the basis of link mining, we improved the PKM by combining link indicator kernel (LIK) and chemical similarity and evaluated the accuracy of these methods. The proposed method obtained an average area under the precision-recall curve (AUPR) value of 0.562, which was higher than that achieved by the conven- tional Gaussian interaction profile (GIP) method (0.425), and the calculation time was only increased by a few percent. Keywords: virtual screening; compound-protein interactions (CPIs); pairwise kernel; link mining; link indicator kernels (LIKs) 1 Introduction Virtual screening (VS), in which drug candidate compounds are selected by a computational method, is one of the main processes in the early stages of drug dis- covery.
    [Show full text]
  • Endogenous Metabolites in Drug Discovery: from Plants to Humans
    Endogenous Metabolites in Drug Discovery: from Plants to Humans Joaquim Olivés Farrés TESI DOCTORAL UPF / ANY 201 6 DIRECTOR DE LA TESI: Dr. Jordi Mestres CEXS Department The research in this T hesis has been carried out at the Systems Pharmacolo gy Group , within the Research Programme on Biomedical Informatics (GRIB) at the Parc de Recerca Biomèdica de Barcelona (PRBB). The research presented in this T hesis has been supported by Ministerio de Ciencia e Innovación project BIO2014 - 54404 - R and BIO2011 - 26669 . Printing funded by the Fundació IMIM’s program “Convocatòria d'ajuts 2016 per a la finalització de tesis doctorals de la Fundació IMIM.” Agraïments Voldria donar les gràcies a tanta gent que em fa por deixar - me ningú. Però per c omençar haig agrair en especial al meu director la tesi, Jordi Mestres, per donar - me la oportunitat de formar part del seu laboratori i poder desenvolupar aquí el treball que aquí es presenta. A més d’oferir l’ajuda necessària sempre que ha calgut. També haig de donar les gràcies a tots els companys del grup de Farmacologia de Sistemes que he anat coneguent durants tots aquests anys en què he estat aquí, en especial en Xavi, a qui li he preguntat mil coses, en Nikita, pels sdfs que m’ha anat llençant a CTL ink, i la Irene i la Cristina, que els seus treballs també m’ajuden a completar la tesis. I cal agrair també a la resta de companys del laboratori, l’Albert, la Viktoria, la Mari Carmen, l’Andreas, en George, l’Eric i l’Andreu; de Chemotargets, en Ricard i en David; i altres membres del GRIB, com són l’Alfons, en Miguel, en Pau, l’Oriol i la Carina.
    [Show full text]
  • Chemogenomics: an Emerging Strategy for Rapid Target and Drug Discovery
    REVIEWS CHEMOGENOMICS: AN EMERGING STRATEGY FOR RAPID TARGET AND DRUG DISCOVERY Markus Bredel*‡ and Edgar Jacoby§ Chemogenomics is an emerging discipline that combines the latest tools of genomics and chemistry and applies them to target and drug discovery. Its strength lies in eliminating the bottleneck that currently occurs in target identification by measuring the broad, conditional effects of chemical libraries on whole biological systems or by screening large chemical libraries quickly and efficiently against selected targets. The hope is that chemogenomics will concurrently identify and validate therapeutic targets and detect drug candidates to rapidly and effectively generate new treatments for many human diseases. Over the past five decades, pharmacological compounds however, that owing to the emergence of various sub- TRANSCRIPTIONAL PROFILING The study of the transcriptome have been identified that collectively target the products specialties of chemogenomics (discussed in the next — the complete set of RNA of ~400–500 genes in the human body; however, only section) and the involvement of several disciplines, it is transcripts that are produced by ~120 of these genes have reached the market as the tar- currently almost impossible to give a simple and com- the genome at any one time — gets of drugs1,2.The Human Genome Project3,4 has mon definition for this research discipline (BOX 1). using high-throughput methods, such as microarray made available many potential new targets for drug In chemogenomics-based drug discovery, large col- analysis. intervention: several thousand of the approximately lections of chemical products are screened for the paral- 30,000–40,000 estimated human genes4 could be associ- lel identification of biological targets and biologically ated with disease and, similarly, several thousand active compounds.
    [Show full text]
  • Toxigence of Anthrax Vaccine Strains
    UDC 579.62 hps://doi.org/10.31548/ujvs2020.03.009 TOXIGENCE OF ANTHRAX VACCINE STRAINS G. A. ZAVIRIYHA, Candidate of Agricultural Sciences hps://orcid.org/0000-0002-46028477 "State Center for Innovave Biotechnology", Kyiv, Ukraine Е-mail: [email protected] U. N. YANENKO, Candidate of Veterinary Sciences hps://orcid.org/ 0000-0001-5678-3356 "State Center for Innovave Biotechnology", Kyiv, Ukraine Е-mail: [email protected], N. I. KOSYANCHUK, Candidate of Veterinary Sciences, Associate Professor Department of Veterinary Hygiene Named Aer Professor A. K. Skorokhodko hps://orcid.org/ 0000-0002- 3055-8107 Naonal University of Life and Environmental Sciences of Ukraine, Kyiv, Ukraine Е-mail: [email protected] Abstract. The arcle presents the results of the studying of anthrax strains and Bacillus anthracis-like strains on the formaon of toxins. We found that anthrax vaccine strains acvely produce exotoxins to the culture fluid. The amount of specific protein is different under the same incubaon condions and depends on the individual characteriscs of the microorganism populaon, because of this, different ters of the toxin are registered. Strain B. anthracis K-79 Z (vaccine) with the same number of planng microbial cells and growing on the same culture medium and at the same temperature produces by two orders of magnitude more exotoxin than strains B. anthracis Tsenkovsky II IBM 92Z (virulent), B. anthracis Stern 34F2, (vaccine), B. anthracis 55 (vaccine), B. anthracis SB (vaccine), B. anthracis Tsenkovsky I (vaccine, аpathogenic). The amount of exotoxin may change if the pH of the medium changes. The acvity of exotoxin producon, when the pH changes, depends on the characteriscs of the anthrax strain.
    [Show full text]
  • Systems Biology 1 Systems Biology
    Systems biology 1 Systems biology Systems biology is a term used to describe a number of trends in bioscience research, and a movement which draws on those trends. Proponents describe systems biology as a biology-based inter-disciplinary study field that focuses on complex interactions in biological systems, claiming that it uses a new perspective (holism instead of reduction). Particularly from year 2000 onwards, the term is used widely in the biosciences, and in a variety of contexts. An often stated ambition of An attempted illustration of the systems approach to biology systems biology is the modeling and discovery of emergent properties, properties of a system whose theoretical description is only possible using techniques which fall under the remit of systems biology. These typically involve cell signaling networks, via long-range allostery[1]. Overview Systems biology can be considered from a number of different aspects: • As a field of study, particularly, the study of the interactions between the components of biological systems, and how these interactions give rise to the function and behavior of that system (for example, the enzymes and metabolites in a metabolic pathway).[2][3] • As a paradigm, usually defined in antithesis to the so-called reductionist paradigm (biological organisation), although fully consistent with the scientific method. The distinction between the two paradigms is referred to in these quotations: "The reductionist approach has successfully identified most of the components and many of the interactions but, unfortunately, offers no convincing concepts or methods to understand how system properties emerge...the pluralism of causes and effects in biological networks is better addressed by observing, through quantitative measures, multiple components simultaneously and by rigorous data integration with mathematical models" Sauer et al[4] "Systems biology...is about putting together rather than taking apart, integration rather than reduction.
    [Show full text]
  • Chemogenomics:Chemogenomics 19/4/07 16:30 Page 57
    Chemogenomics:Chemogenomics 19/4/07 16:30 Page 57 Genomics CHEMOGENOMICS a gene family approach to parallel drug discovery Currently available drugs only target around 500 different proteins4. Recent reports from efforts to sequence the human genome suggest there are tens of thousands of genes1,2 and many more different proteins. Popular estimates of the number of ‘new’ drug targets that will emerge from genomic research range from 2,000 to 5,0003. A critical question as we enter the post-genomic world is: how can the pharmaceutical industry rapidly discover and develop medicines for these new targets to improve the human condition? n the pharmaceutical industry to date, research QSAR, structure-based drug design and informat- By Dr Paul R. Caron, and early development activities have typically ics, have accelerated the drug discovery process4. Dr Michael D. Ibeen organised according to therapeutic area. Dramatically new and different drug discovery Mullican, Dr Robert In organising their drug discovery efforts in this approaches, however, are needed to take full D. Mashal, Dr Keith P. way, companies have sought to create efficiency by advantage of the massive influx of targets being Wilson, Dr Michael S. building a critical mass of expertise and experience elucidated through genomic research. Simply stat- Su and Dr Mark A. in the biology of related diseases. Over the past 20- ed, a therapeutic area focus and a single target Murcko 30 years this organisational approach has proved drug discovery approach do not create enough effi- successful for many companies. While there is no ciency to allow companies to keep pace with the doubt that this strategy produces some synergies in massive inflows of new target information.
    [Show full text]
  • An Emerging Strategy for Rapid Target and Drug Discovery
    R E V I E W S CHEMOGENOMICS: AN EMERGING STRATEGY FOR RAPID TARGET AND DRUG DISCOVERY Markus Bredel*‡ and Edgar Jacoby§ Chemogenomics is an emerging discipline that combines the latest tools of genomics and chemistry and applies them to target and drug discovery. Its strength lies in eliminating the bottleneck that currently occurs in target identification by measuring the broad, conditional effects of chemical libraries on whole biological systems or by screening large chemical libraries quickly and efficiently against selected targets. The hope is that chemogenomics will concurrently identify and validate therapeutic targets and detect drug candidates to rapidly and effectively generate new treatments for many human diseases. Over the past five decades, pharmacological compounds however, that owing to the emergence of various sub- TRANSCRIPTIONAL PROFILING The study of the transcriptome have been identified that collectively target the products specialties of chemogenomics (discussed in the next — the complete set of RNA of ~400–500 genes in the human body; however, only section) and the involvement of several disciplines, it is transcripts that are produced by ~120 of these genes have reached the market as the tar- currently almost impossible to give a simple and com- the genome at any one time — gets of drugs1,2. The Human Genome Project3,4 has mon definition for this research discipline (BOX 1). using high-throughput methods, such as microarray made available many potential new targets for drug In chemogenomics-based drug discovery, large col- analysis. intervention: several thousand of the approximately lections of chemical products are screened for the paral- 30,000–40,000 estimated human genes4 could be associ- lel identification of biological targets and biologically ated with disease and, similarly, several thousand active compounds.
    [Show full text]