Sensor potency of the moonlighting enzyme-decorated cytoskeleton

Background: There is extensive evidence for the interaction of metabolic enzymes with the eukaryotic cytoskeleton. The significance of these interactions is far from clear. Presentation of the hypothesis: In the cytoskeletal integrative sensor hypothesis presented here, the cytoskeleton senses and integrates the general metabolic activity of the cell. This activity depends on the binding to the cytoskeleton of enzymes and, depending on the nature of the enzyme, this binding may occur if the enzyme is either active or inactive but not both. This enzyme-binding is further proposed to stabilize microtubules and microfilaments and to alter rates of GTP and ATP hydrolysis and their levels. Testing the hypothesis: Evidence consistent with the cytoskeletal integrative sensor hypothesis is presented in the case of glycolysis. Several testable predictions are made. There should be a relationship between post-translational modifications of tubulin and of actin and their interaction with metabolic enzymes. Different conditions of cytoskeletal dynamics and enzyme-cytoskeleton binding should reveal significant differences in local and perhaps global levels and ratios of ATP and GTP. The different functions of moonlighting enzymes should depend on cytoskeletal binding. Implications of the hypothesis: The physical and chemical effects arising from metabolic sensing by the cytoskeleton would have major consequences on cell shape, dynamics and cell cycle progression. The hypothesis provides a framework that helps the significance of the enzyme-decorated cytoskeleton be determined

ABOUT THE COMPLEXITY OF LIVING SYSTEMS MODELS

In this paper we attempt an overview of the philosophical implications of complex systems thought, and investigate how this alternative viewpoint affects our attempts to design and utilise models for living systems. We classify the types of complex system that relate to self-organisation. The overall requirements for self-organising modeling are considered and some alternative ways of looking at some specific problems that may arise are explored. As a novelty, the paper proposes various ways of moving forward in the area of practical model design.complex systems, models, practical desing

A stochastic automaton shows how enzyme assemblies may contribute to metabolic efficiency

<p>Abstract</p> <p>Background</p> <p>The advantages of grouping enzymes into metabolons and into higher order structures have long been debated. To quantify these advantages, we have developed a stochastic automaton that allows experiments to be performed in a virtual bacterium with both a membrane and a cytoplasm. We have investigated the general case of transport and metabolism as inspired by the phosphoenolpyruvate:sugar phosphotransferase system (PTS) for glucose importation and by glycolysis.</p> <p>Results</p> <p>We show that PTS and glycolytic metabolons can increase production of pyruvate eightfold at low concentrations of phosphoenolpyruvate. A fourfold increase in the numbers of enzyme EI led to a 40% increase in pyruvate production, similar to that observed <it>in vivo </it>in the presence of glucose. Although little improvement resulted from the assembly of metabolons into a hyperstructure, such assembly can generate gradients of metabolites and signaling molecules.</p> <p>Conclusion</p> <p><it>in silico </it>experiments may be performed successfully using stochastic automata such as HSIM (Hyperstructure Simulator) to help answer fundamental questions in metabolism about the properties of molecular assemblies and to devise strategies to modify such assemblies for biotechnological ends.</p

Computing with bacterial constituents, cells and populations: from bioputing to bactoputing

The relevance of biological materials and processes to computing—aliasbioputing—has been explored for decades. These materials include DNA, RNA and proteins, while the processes include transcription, translation, signal transduction and regulation. Recently, the use of bacteria themselves as living computers has been explored but this use generally falls within the classical paradigm of computing. Computer scientists, however, have a variety of problems to which they seek solutions, while microbiologists are having new insights into the problems bacteria are solving and how they are solving them. Here, we envisage that bacteria might be used for new sorts of computing. These could be based on the capacity of bacteria to grow, move and adapt to a myriad different fickle environments both as individuals and as populations of bacteria plus bacteriophage. New principles might be based on the way that bacteria explore phenotype space via hyperstructure dynamics and the fundamental nature of the cell cycle. This computing might even extend to developing a high level language appropriate to using populations of bacteria and bacteriophage. Here, we offer a speculative tour of what we term bactoputing, namely the use of the natural behaviour of bacteria for calculating

The Eukaryotic Cell Originated in the Integration and Redistribution of Hyperstructures from Communities of Prokaryotic Cells Based on Molecular Complementarity

In the “ecosystems-first” approach to the origins of life, networks of non-covalent assemblies of molecules (composomes), rather than individual protocells, evolved under the constraints of molecular complementarity. Composomes evolved into the hyperstructures of modern bacteria. We extend the ecosystems-first approach to explain the origin of eukaryotic cells through the integration of mixed populations of bacteria. We suggest that mutualism and symbiosis resulted in cellular mergers entailing the loss of redundant hyperstructures, the uncoupling of transcription and translation, and the emergence of introns and multiple chromosomes. Molecular complementarity also facilitated integration of bacterial hyperstructures to perform cytoskeletal and movement functions

A Prerequisite for Life

The complex physicochemical structures and chemical reactions in living organism have some common features: (1) The life processes take place in the cytosol in the cells, which, from a physicochemical point of view is an emulsion of biomolecules in a dilute aqueous suspension. (2) All living systems are homochiral with respect to the units of amino acids and carbohydrates, but (some) proteins are chiral unstable in the cytosol. (3) And living organism are mortal. These three common features together give a prerequisite for the prebiotic self-assembly at the start of the Abiogenesis. Here we argue , that it all together indicates, that the prebiotic self-assembly of structures and reactions took place in a more saline environment, whereby the homochirality of proteins not only could be obtained, but also preserved. A more saline environment for the prebiotic self-assembly of organic molecules and establishment of biochemical reactions could have been the hydrothermal vents

Overcoming the Newtonian Paradigm: The Unfinished Project of Theoretical Biology from a Schellingian Perspective

Defending Robert Rosen’s claim that in every confrontation between physics and biology it is physics that has always had to give ground, it is shown that many of the most important advances in mathematics and physics over the last two centuries have followed from Schelling’s demand for a new physics that could make the emergence of life intelligible. Consequently, while reductionism prevails in biology, many biophysicists are resolutely anti-reductionist. This history is used to identify and defend a fragmented but progressive tradition of anti-reductionist biomathematics. It is shown that the mathematicoephysico echemical morphology research program, the biosemiotics movement, and the relational biology of Rosen, although they have developed independently of each other, are built on and advance this antireductionist tradition of thought. It is suggested that understanding this history and its relationship to the broader history of post-Newtonian science could provide guidance for and justify both the integration of these strands and radically new work in post-reductionist biomathematics

In search of an evolutionary coding style

In the near future, all the human genes will be identified. But understanding the functions coded in the genes is a much harder problem. For example, by using block entropy, one has that the DNA code is closer to a random code then written text, which in turn is less ordered then an ordinary computer code; see \cite{schmitt}. Instead of saying that the DNA is badly written, using our programming standards, we might say that it is written in a different style -- an evolutionary style. We will suggest a way to search for such a style in a quantified manner by using an artificial life program, and by giving a definition of general codes and a definition of style for such codes.Comment: 14 pages, 7 postscript figure

Molecules, Cells and Minds: Aspects of Bioscientific Explanation

In this thesis I examine a number of topics that bear on explanation and understanding in molecular and cell biology, in order to shed new light on explanatory practice in those areas and to find novel angles from which to approach relevant philosophical debates. The topics I look at include mechanism, emergence, cellular complexity, and the informational role of the genome. I develop a perspective that stresses the intimacy of the relations between ontology and epistemology. Whether a phenomenon looks mechanistic, or complex, or indeed emergent, is largely an epistemic matter, yet has an objective basis in features of the world. After reviewing several concepts of mechanism I consider the influential recent account of Machamer, Darden and Craver (MDC). That account makes interesting proposals concerning the relationship between mechanistic explanation and intelligibility, which are consistent with the results of the investigation I undertake into the science surrounding protein folding. In relation to a number of other issues pertaining to biological systems I conclude that the MDC account is insufficiently nuanced, however, leading me to outline an alternative approach to mechanism. This emphasizes the importance of structure—function relations and addresses issues raised by reflection on the nature of cellular complexity. These include the distinction between structure and process and the different possible bases on which system organization may be maintained. The account I give of emergence construes the phenomenon in terms of psychological deficit: phenomena are emergent when we lack the capacity to trace through and model their causal structures using our cognitive schemas. I conclude by developing these ideas into a preliminary and partial account of explanation and understanding. This aspires to cover the significant fraction of work in molecular and cell biology that correlates biological structures, processes and functions by visualizing phenomena and making them imaginable