This volume contains cutting-edge reviews by world-leading experts on the systems biology of microorganisms. As well as covering theoretical approaches and mathematical modelling this book includes case studies on single microbial species of bacteria and archaea, and explores the systems analysis of microbial phenomena such as chemotaxis and phagocytosis. Topics covered include mathematical models for systems biology, systems biology of Escherichia coli metabolism, bacterial chemotaxis, systems biology of infection, host-microbe interactions, phagocytosis, system-level study of metabolism in M.
This book presents a range of current research topics in biological network modeling, as well as its application in studies on human hosts, pathogens, and diseases. Systems biology is a rapidly expanding field that involves the study of biological systems through the mathematical modeling and analysis of large volumes of biological data. Gathering contributions from renowned experts in the field, some of the topics discussed in depth here include networks in systems biology, the computational modeling of multidrug-resistant bacteria, and systems biology of cancer. Given its scope, the book is intended for researchers, advanced students, and practitioners of systems biology. The chapters are research-oriented, and present some of the latest findings on their respective topics.
A brilliant young scientist introduces us to the fascinating field that is changing our understanding of how the body works and the way we can approach healing. SYSTEMATIC is the first book to introduce general readers to systems biology, which is improving medical treatments and our understanding of living things. In traditional bottom-up biology, a biologist might spend years studying how a single protein works, but systems biology studies how networks of those proteins work together--how they promote health and how to remedy the situation when the system isn't functioning properly. Breakthroughs in systems biology became possible only when powerful computer technology enabled researchers to process massive amounts of data to study complete systems, and has led to progress in the study of gene regulation and inheritance, cancer drugs personalized to an individual's genetically unique tumor, insights into how the brain works, and the discovery that the bacteria and other microbes that live in the gut may drive malnutrition and obesity. Systems biology is allowing us to understand more complex phenomena than ever before. In accessible prose, SYSTEMATIC sheds light not only on how systems within the body work, but also on how research is yielding new kinds of remedies that enhance and harness the body's own defenses.
Many potential applications of synthetic and systems biology are relevant to the challenges associated with the detection, surveillance, and responses to emerging and re-emerging infectious diseases. On March 14 and 15, 2011, the Institute of Medicine's (IOM's) Forum on Microbial Threats convened a public workshop in Washington, DC, to explore the current state of the science of synthetic biology, including its dependency on systems biology; discussed the different approaches that scientists are taking to engineer, or reengineer, biological systems; and discussed how the tools and approaches of synthetic and systems biology were being applied to mitigate the risks associated with emerging infectious diseases. The Science and Applications of Synthetic and Systems Biology is organized into sections as a topic-by-topic distillation of the presentations and discussions that took place at the workshop. Its purpose is to present information from relevant experience, to delineate a range of pivotal issues and their respective challenges, and to offer differing perspectives on the topic as discussed and described by the workshop participants. This report also includes a collection of individually authored papers and commentary.
This book introduces the concept of bacterial communication systems from a mathematical modeling point of view. It sheds light on the research undertaken in the last three decades, and the mathematical models that have been proposed to understand the underlying mechanism of such systems. These communication systems are related to quorum sensing mechanisms and quorum sensing regulated processes such as biofilm formation, gene expression, bioluminescence, swarming and virulence. The book further describes the phenomenon of noise, and discusses how noise plays a crucial role in gene expression and the quorum sensing circuit operationusing a set of tools like frequency domain analysis, power spectral density, stochastic simulation and the whitening effect. It also explores various aspects of synthetic biology (related to bacterial communication), such as genetic toggle switch, bistable gene regulatory networks, transcriptional repressor systems, pattern formation, synthetic cooperation, predator-prey synthetic systems, dynamical quorum sensing, synchronized quorum of genetic clocks, role of noise in synthetic biology, the Turing test and stochastic Turing test.
The systems biology of microbial infections aims at describing and analysing the confrontation of the host with bacterial and fungal pathogens. It intends to understand and to model the interaction of the host, in particular the immune system of humans or animals, with components of pathogens. This comprises experimental studies that provide spatio-temporal data from monitoring the response of host and pathogenic cells to perturbations or when interacting with each other, as well as the integrative analysis of genome-wide data from both the host and the pathogen. In perspective, the host-pathogen interaction should be described by a combination of spatio-temporal models with interacting molecular networks of the host and the pathogen. The aim is to unravel the main mechanisms of pathogenicity, to identify diagnostic biomarkers and potential drug targets, and to explore novel strategies for personalized therapy by computer simulations. Some microorganisms are part of the normal microbial flora, existing either in a mutualistic or commensal relationship with the host. Microorganisms become pathogenic if they posses certain physiological characteristics and virulence determinants as well as capabilities for immune evasion. Despite the different pathogenesis of infections, there are several common traits: (1) Before infection, pathogens must be able to overcome (epithelial) barriers. The infection starts by adhesion and colonization and is followed by entering of the pathogen into the host through the mucosa or (injured) skin. (2) Next, infection arises if the pathogen multiplies and overgrows the normal microbial flora, either at the place of entrance or in deeper tissue layers or organs. (3) After the growth phase, the pathogen damages the host’s cells, tissues and organs by producing toxins or destructive enzymes. Thus, systems biology of microbial infection comprises all levels of the pathogen and the host’s immune system. The investigation may start with the pathogen, its adhesion and colonization at the host, its interaction with host cell types e.g. epithelia cells, dendritic cells, macrophages, neutrophils, natural killer cells, etc. Because infection diseases are mainly found in patients with a weakened immune system, e.g. reduced activities of immune effector cells or defects in the epithelial barriers, systems biology of infection can also start with modelling of the immune defence including innate and adaptive immunity. Systems biological studies comprise both experimental and theoretical approaches. The experimental studies may be dedicated to reveal the relevance of certain genes or proteins in the above mentioned processes on the side of the pathogen and/or the host by applying functional and biochemical analyses based on knock-out mutants and knock- down experiments. At the theoretical, i.e. mathematical and computational, side systems biology of microbial infection comprises: (1) modelling of molecular mechanisms of bacterial or fungal infections, (2) modelling of non-protective and protective immune defences against microbial pathogens to generate information for possible immune therapy approaches, (3) modelling of infection dynamics and identification of biomarkers for diagnosis and for individualized therapy, (4) identifying essential virulence determinants and thereby predicting potential drug targets.
Beginning with the germ theory of disease in the 19th century and extending through most of the 20th century, microbes were believed to live their lives as solitary, unicellular, disease-causing organisms . This perception stemmed from the focus of most investigators on organisms that could be grown in the laboratory as cellular monocultures, often dispersed in liquid, and under ambient conditions of temperature, lighting, and humidity. Most such inquiries were designed to identify microbial pathogens by satisfying Koch's postulates.3 This pathogen-centric approach to the study of microorganisms produced a metaphorical "war" against these microbial invaders waged with antibiotic therapies, while simultaneously obscuring the dynamic relationships that exist among and between host organisms and their associated microorganisms-only a tiny fraction of which act as pathogens. Despite their obvious importance, very little is actually known about the processes and factors that influence the assembly, function, and stability of microbial communities. Gaining this knowledge will require a seismic shift away from the study of individual microbes in isolation to inquiries into the nature of diverse and often complex microbial communities, the forces that shape them, and their relationships with other communities and organisms, including their multicellular hosts. On March 6 and 7, 2012, the Institute of Medicine's (IOM's) Forum on Microbial Threats hosted a public workshop to explore the emerging science of the "social biology" of microbial communities. Workshop presentations and discussions embraced a wide spectrum of topics, experimental systems, and theoretical perspectives representative of the current, multifaceted exploration of the microbial frontier. Participants discussed ecological, evolutionary, and genetic factors contributing to the assembly, function, and stability of microbial communities; how microbial communities adapt and respond to environmental stimuli; theoretical and experimental approaches to advance this nascent field; and potential applications of knowledge gained from the study of microbial communities for the improvement of human, animal, plant, and ecosystem health and toward a deeper understanding of microbial diversity and evolution. The Social Biology of Microbial Communities: Workshop Summary further explains the happenings of the workshop.
This volume details protocols that cover the broad arsenal of techniques used to study a secretion system from A to Z. Chapters focus on identifying and localizing the different subunits, defining interactions within subunits, monitoring conformational changes, purifying and imaging of large complexes, defining the assembly pathway by fluorescence microscopy and the role of energy during assembly and/or secretion, identifying secreted effectors as well as reporters to follow effector transport. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Bacterial Protein Secretion Systems: Methods and Protocol aims to provide techniques that are not restricted to the study of secretion systems but are also of specific interest for any researcher interested on multi-protein complexes of the bacterial cell envelope.
The book aims to introduce the reader to the emerging field of Evolutionary Systems Biology, which approaches classical systems biology questions within an evolutionary framework. An evolutionary approach might allow understanding the significance of observed diversity, uncover “evolutionary design principles” and extend predictions made in model organisms to others. In addition, evolutionary systems biology can generate new insights into the adaptive landscape by combining molecular systems biology models and evolutionary simulations. This insight can enable the development of more detailed mechanistic evolutionary hypotheses.
