Rewriting systems and the modelling of biological systems

This paper gives a brief survey of the use of algebraic rewriting systems for modelling and simulating various biological processes, particularly at the cellular level.     

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.     

Homology and the hierarchy of biological systems

Homology is the similarity between organisms due to common ancestry. Introduced by Richard Owen in 1843 in a paper entitled "Lectures on comparative anatomy and physiology of the invertebrate animals", the concept of homology predates Darwin's "Origin of Species" and has been very influential throughout the history of evolutionary biology. Although homology is the central concept of all comparative biology and provides a logical basis for it, the definition of the term and the criteria of its application remain controversial. Here, I will discuss homology in the context of the hierarchy of biological organization. I will provide insights gained from an exemplary case study in evolutionary developmental biology that indicates the uncoupling of homology at different levels of biological organization. I argue that continuity and hierarchy are separate but equally important issues of homology.     

Evolution and classification of the CRISPR-Cas systems

The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of evolution for both the cas genes and the unique spacer content. Here, we provide an updated analysis of the evolutionary relationships between CRISPR-Cas systems and Cas proteins. Three major types of CRISPR-Cas system are delineated, with a further division into several subtypes and a few chimeric variants. Given the complexity of the genomic architectures and the extremely dynamic evolution of the CRISPR-Cas systems, a unified classification of these systems should be based on multiple criteria. Accordingly, we propose a 'polythetic' classification that integrates the phylogenies of the most common cas genes, the sequence and organization of the CRISPR repeats and the architecture of the CRISPR-cas loci.     

Cross-talk of the renin-angiotensin and kallikrein-kinin systems

The renin-angiotensin (RAS) and kallikrein-kinin (KKS) systems play a key role in multiple physiological and pathophysiological conditions, including growth and development, inflammation, blood pressure regulation and control of renal function. In many instances, kinins and angiotensin II work together, e.g., during development, whereas they oppose each other's actions in the regulation of vascular tone and renal function. The RAS and KKS systems also interact at multiple levels, so that changes in the activity of one system greatly impact the activity of the other. The purpose of this brief review is to highlight recent knowledge regarding interactions at the cellular and molecular levels between the two systems, with an emphasis on the coordinate developmental regulation of these phylogenetically conserved vasoactive systems.     

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.     

On systems thinking, systems biology, and the in silico plant

The recent summary report of a Department of Energy Workshop on Plant Systems Biology (P.V. Minorsky [2003] Plant Physiol 132: 404-409) offered a welcomed advocacy for systems analysis as essential in understanding plant development, growth, and production. The goal of the Workshop was to consider methods for relating the results of molecular research to real-world challenges in plant production for increased food supplies, alternative energy sources, and environmental improvement. The rather surprising feature of this report, however, was that the Workshop largely overlooked the rich history of plant systems analysis extending over nearly 40 years (Sinclair and Seligman, 1996) that has considered exactly those challenges targeted by the Workshop. Past systems research has explored and incorporated biochemical and physiological knowledge into plant simulation models from a number of perspectives. The research has resulted in considerable understanding and insight about how to simulate plant systems and the relative contribution of various factors in influencing plant production. These past activities have contributed directly to research focused on solving the problems of increasing biomass production and crop yields. These modeling approaches are also now providing an avenue to enhance integration of molecular genetic technologies in plant improvement (Hammer et al., 2002).     

Influence of health care systems on the market for picture archiving and communication systems

An analysis is given of the relation between health care systems and the PACS market. Two driving forces exist in the market: quality and price. It is argued that the quality driven market is mainly independent of the health care system and will be the force that drives the introduction of the health care system and will be the force that drives the introduction of PACS in the forthcoming years. Finally a change of focus is suggested from only archiving and communication to a more general concept of image networking, serving more goals than only the goal of working filmlessly.     

The renin-angiotensin and the kallikrein-kinin systems

The renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS) each encompasses a large number of molecules, with several participating in both systems. The RAS generates a family of bioactive angiotensin peptides with varying biological activities. These include angiotensin-(1-8) (Ang II), angiotensin-(2-8) (Ang III), angiotensin-(3-8) (Ang IV), and angiotensin-(1-7) [Ang-(1-7)]. Ang II and Ang III act on type 1 (AT(1)) and type 2 (AT(2)) angiotensin receptors, whereas, Ang IV and Ang-(1-7) act on their own receptors. The KKS also generates a family of bioactive peptides with varying biological activities. These include hydroxylated and non-hydroxylated bradykinin and kallidin peptides and their carboxypeptidase metabolites des-Arg(9)-bradykinin and des-Arg(10)-kallidin. Whereas bradykinin and kallidin act mainly via the type 2 bradykinin (B(2)) receptor, des-Arg(9)-bradykinin and des-Arg(10)-kallidin act mainly via the type 1 bradykinin (B(1)) receptor. The AT(1) receptor forms heterodimers with the AT(2) and B(2) receptors and there is cross talk between the AT(1) and epidermal growth factor receptors. The B(2) receptor also interacts with angiotensin converting enzyme and nitric oxide synthase. Both angiotensin and kinin peptides are metabolised by many different peptidases that are important determinants of the activities of the RAS and KKS, and several of which participate in both systems.     

Individuals and the evolution of biological and cultural systems

Recently, it has been suggested that anthropologists could more effectively build scientific theories of cultural evolution by reference to biology rather than social science. In this way, the evolution of cultures might be more usefully viewed as an anolog to the evolution of species. In systematic biology, however, the nature of species continues to be the subject of a long-standing duality of thought. This duality is analogous to the longstanding conflict in anthropology over the nature of culture. We argue, by analogy to Michael Ghiselin’s work on species, that a culture is an individual, not a class, and that cultures, like other individual entities, evolve. This view is highly concordant with concepts of culture formulated in earlier decades of this century. It has also been the philosophical orientation of American archaeology for approximately the last 25 years. We conclude that both biology and anthropology have an equal potential of contributing to a general evolutionary theory.     

Catalytic RNA and the origin of genetic systems

The recent discovery of catalytic RNA molecules has provoked enormous interest in the origin of life and has given rise to new speculations about how living systems developed on the primitive earth. Here we outline why the discovery of catalytic RNA molecules has profound evolutionary implications, and then go on to discuss models for the emergence of metabolic complexity and protein synthesis in a primitive 'RNA world', emphasizing the constraints imposed on such models by genetical arguments.     

Parasitic systems and the structure of parasite populations

 The analysis of population systems is carried out on the basis of the spatial and functional classification of populations developed by V.N. Beklemishev. The population system is a functional part of a particular community. Steady interrelationships between population systems of different species within the community (referred to as ”community links”) appear to be a prerequisite for the formation of a complex of population systems. A prominent example of this is the parasitic system. The parasitic system is the population system of a parasite with all the connected populations of its hosts. The complexity of a parasitic system depends on: (1) peculiarities of the life cycle of the parasite, since its population system is the organizing component of the parasitic system and (2) subdivision of the environment for the parasites. The first trait is discussed from the standpoint of the phase structure of populations, which is clearly seen in parasites. The second one comprises the organization of the parasites’ environment according to the scale of variability (interspecies, interpopulation or intrapopulation) of hosts. These make it possible to recognize spatial and functional parts in the framework of the parasitic system. A critical review of the terminology is presented together with a list of the pertaining vocabulary. Received: 15 January 1998 / Accepted: 15 October 1998