From systems biology to systems biomedicine

Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to furthermore translate mechanistic insights in biological systems to clinical application, with the central aim of improving patients' quality of life. The challenge is to find theoretically well-chosen models for the contextually correct and intelligible representation of multi-scale biological systems. In this review, we discuss the current state of Systems Biology, highlight the emergence of Systems Biomedicine, and highlight some of the topics and views that we think are important for the efficient application of Systems Theory in Biomedicine.     

Bimolecular systems: III. Catalytic systems

Amplification effect in the catalytic bimolecular systems is a consequence of the kinetic characteristic of the catalyst. Two types of the coefficient of amplification are defined. The applicability of these definitions is given by the type of the bimolecular system. In a simple example it is shown that the concept of amplification is meaningful in these systems. Furthermore, two rules, analogous to those for a coupling of amplifiers, are derived for the two basic modes of coupling of catalytic systems. Thus, in biological systems the catalytic reactions may be regarded as biologically effective amplifiers.     

Putting the systems back into systems biology

In recent years the term "systems biology" has become widespread in the biological literature, but most of the papers in which these words appear have surprisingly little to do with older notions of biological systems: they often seem to imply little more than reductionist biology applied on a large scale, with a little attention to interactions between some of the components, but with minimal attention to the kinetic properties of enzymes, which supplied much of the reductionist foundation of biochemistry. A systemic approach to biology ought to put the emphasis on the entire system; insofar as it is concerned with components at all, it is to explain their roles in meeting the needs of the system as a whole. Genuinely systemic thinking allows us to understand how biochemical systems are regulated, and why clumsy attempts to manipulate them for biotechnological purposes may fail. At a more abstract level, it is necessary for understanding the nature of life, because as long as an organism is treated as no more than a collection of components, one cannot ask the right questions, and certainly cannot answer them.     

Taking a systems approach to ecological systems

Increasingly, there is interest in a systems‐level understanding of ecological problems, which requires the evaluation of more complex, causal hypotheses. In this issue of the Journal of Vegetation Science, Soliveres et al. use structural equation modeling to test a causal network hypothesis about how tree canopies affect understorey communities. Historical analysis suggests structural equation modeling has been under‐utilized in ecology.     

Contractile injection systems of bacteriophages and related systems

Contractile tail bacteriophages, or myobacteriophages, use a sophisticated biomolecular structure to inject their genome into the bacterial host cell. This structure consists of a contractile sheath enveloping a rigid tube that is sharpened by a spike‐shaped protein complex at its tip. The spike complex forms the centerpiece of a baseplate complex that terminates the sheath and the tube. The baseplate anchors the tail to the target cell membrane with the help of fibrous proteins emanating from it and triggers contraction of the sheath. The contracting sheath drives the tube with its spiky tip through the target cell membrane. Subsequently, the bacteriophage genome is injected through the tube. The structural transformation of the bacteriophage T4 baseplate upon binding to the host cell has been recently described in near‐atomic detail. In this review we discuss structural elements and features of this mechanism that are likely to be conserved in all contractile injection systems (systems evolutionary and structurally related to contractile bacteriophage tails). These include the type VI secretion system (T6SS), which is used by bacteria to transfer effectors into other bacteria and into eukaryotic cells, and tailocins, a large family of contractile bacteriophage tail‐like compounds that includes the P. aeruginosa R‐type pyocins.     

Motor systems

The field of motor control has broadened considerably over the past decade. Increasingly detailed information has accrued about the cellular and molecular processes involved in motor pattern generation and motor learning while, at the other extreme, the comparison of studies in humans and monkeys has begun to bridge the gap between cognitive and motor functions. The most striking feature of recent research has been the intense use of electrophysiological procedures in behaving monkeys and non-invasive imaging procedures in humans to elucidate details of sensory-motor transformations and the functional roles of different brain regions in the learning, planning and execution of movements.     

Memory systems

Two recent findings are summarized here that bear on the organization of memory and brain systems. First, the capacity for simple recognition of familiarity (a form of declarative memory) depends on the hippocampal region in both humans and nonhuman primates. Second, probabilistic classification learning (a form of nondeclarative memory akin to habit learning) depends on the caudate nucleus and putamen. These findings are related to the classification of long-term memory and current understanding of the participating brain systems.     

Sensory systems

Our understanding of sensory systems has grown impressively in recent years as a result of intense efforts to characterize the mechanisms underlying perception. A large body of evidence has accrued regarding the processes through which sensory information at the biochemical, electrophysiological, and systems levels contributes to the conscious experience of a stimulus. Our efforts to understand the function of sensory systems have been aided by the development of new techniques, including powerful methods of molecular biology, refined short- and long-term approaches to recording from single and multiple neurons, and non-invasive neuroimaging techniques that allow us to study activity within the human brain while subjects perform a variety of cognitive tasks. In future research, the last approach is likely to form a bridge between the large body of electrophysiological knowledge acquired in animal experiments and that currently being obtained in human imaging research.     

Host-vector systems

In 1980 it was only possible to express foreign genes in bacteria and a few easily cultured animal cells. During the subsequent eight years specialized vectors have been developed to allow the genetic manipulation of a wide range of both prokaryotes and eukaryotes. One of the major goals of biotechnology in 1980 was to use host cells as 'factories' for the production of proteins that were only available in minute quantities from natural sources. This has already lead to a new generation of pharmaceutical products. Advances in our understanding of host-vector systems have defined new goals. The basic concepts of expression vector design will be illustrated. Some of the new goals are discussed with particular reference to the exploitation of novel host-vector systems to develop vaccines and anti-viral agents against AIDS.     

Glutaredoxin systems

Glutaredoxins utilize the reducing power of glutathione to maintain and regulate the cellular redox state and redox-dependent signaling pathways, for instance, by catalyzing reversible protein S-glutathionylation. Due to the general importance of these processes, glutaredoxins have been implied in various physiological and disease-related conditions, such as immune defense, cardiac hypertrophy, hypoxia-reoxygenation insult, neurodegeneration and cancer development, progression as well as treatment. The past years have seen an impressive gain of knowledge regarding new glutaredoxin systems and functions. This is true both with respect to new functions in redox regulation and also with respect to unexpected new ties to iron metabolism and iron-sulfur cluster biosynthesis. The aim of this review is to provide a state-of-the-art overview over these recent discoveries with a focus on aspects related to human health.     

Glutaredoxin systems

Glutaredoxins utilize the reducing power of glutathione to maintain and regulate the cellular redox state and redox-dependent signaling pathways, for instance, by catalyzing reversible protein S-glutathionylation. Due to the general importance of these processes, glutaredoxins have been implied in various physiological and disease-related conditions, such as immune defense, cardiac hypertrophy, hypoxia-reoxygenation insult, neurodegeneration and cancer development, progression as well as treatment. The past years have seen an impressive gain of knowledge regarding new glutaredoxin systems and functions. This is true both with respect to new functions in redox regulation and also with respect to unexpected new ties to iron metabolism and iron–sulfur cluster biosynthesis. The aim of this review is to provide a state-of-the-art overview over these recent discoveries with a focus on aspects related to human health.     

Dynamic systems

A report of the Wellcome Trust Functional Genomics and Systems Biology Conference, Hinxton, UK, 29 November to 1 December 2011.     

Sensory systems

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Neurobiology.     

Sensory systems

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Neurobiology.