Biomedical subjects

Vic Norris

Publications and source records attributed to Vic Norris.

7 recordsLinked to original sources

PubMed2003

Networks as constrained thermodynamic systems.

We show how a network of interconnections between nodes can be constructed to have a specified distribution of nodal degrees. This is achieved by treating the network as a thermodynamic system subject to constraints and then rewiring the system to maintain the constraints while increasing the entropy. The general construction is given and illustrated by the simple example of an exponential network. By considering the constraints as a cost function analogous to an internal energy, we obtain a characterisation of the correspondence between the intensive and extensive variables of the network. Applied to networks in living organisms, this approach may lead to macroscopic variables useful in characterising living systems.

Entropy↗

PubMed2003

Modelling autocatalytic networks with artificial microbiology.

Cells can usefully be equated to autocatalytic networks that increase in mass and then divide. To begin to model relationships between autocatalytic networks and cell division, we have written a program of artificial chemistry that simulates a cell fed by monomers. These monomers are symbols that can be assembled into linear (non-branched) polymers to give different lengths. A reaction is catalysed by a particular polymer or 'enzyme' that may itself be a reactant of that reaction (autocatalysis). These reactions are only studied within the confines of the 'cell' or 'reaction chamber'. There is a flux of material through the cell and eventually the mass of polymers reaches a threshold at which we analyse the cell. Our results indicate a similarity between the connectivity of the reaction network and that of real metabolic networks. Developing the model will entail attributing increased probabilities of reactions to polymers that are colocalised to evaluate the consequences of the dynamics of large assemblies of diverse molecules (hyperstructures) and of cell division.

Bacteria↗

PubMed2003

A strand-specific model for chromosome segregation in bacteria.

Chromosome separation and segregation must be executed within a bacterial cell in which the membrane and cytoplasm are highly structured. Here, we develop a strand-specific model based on each of the future daughter chromosomes being associated with a different set of structures or hyperstructures in an asymmetric cell. The essence of the segregation mechanism is that the genes on the same strand in the parental cell that are expressed together in a hyperstructure continue to be expressed together and segregate together in the daughter cell. The model therefore requires an asymmetric distribution of classes of genes and of binding sites and other structures on the strands of the parental chromosome. We show that the model is consistent with the asymmetric distribution of highly expressed genes and of stress response genes in Escherichia coli and Bacillus subtilis. The model offers a framework for interpreting data from genomics.

Bacillus subtilis↗

PubMed2002

Hypothesis: a phospholipid translocase couples lateral and transverse bilayer asymmetries in dividing bacteria.

Cell division in bacteria such as Escherichia coli entails changes in the radii of curvature of the invaginating cytoplasmic membrane which culminate in rearrangements of its monolayers. Division therefore risks perturbing transverse and lateral asymmetries and compromising membrane integrity. This leads us to propose that a strong selective pressure exists for a phospholipid translocator that would transfer phospholipids across the cytoplasmic membrane so as to both demarcate the division site and mediate lipid composition during division. This translocase has an affinity for phospholipids with small headgroups and unsaturated acyl chains which it translocates so as to (1) generate changes in the radius of curvature, (2) facilitate septum formation, (3) minimise bilayer disruption during fusion and (4) prevent septum formation at old or inappropriate division sites. We discuss briefly possible candidates for this translocase including ABC transporters and proteins localised to the division site.

Bacteria↗

PubMed2002

Hypothesis: hyperstructures regulate initiation in Escherichia coli and other bacteria.

Hyperstructures or modules have been proposed to constitute a level of organisation intermediate between macromolecules and whole cells. In this model of intracellular organisation, hyperstructures compete and collaborate for existence within the membrane and cytoplasm. Those directly involved in the cell cycle include initiation, replication and division hyperstructures based on DnaA, SeqA and the 2-minute cluster, respectively. During the run-up to initiation, the mass to DNA ratio increases and, we contend, differential gene expression leads to some hyperstructures becoming more active and stable than others. This results in a drop in the diversity of hyperstructures, some of which release DnaA as they dissociate, and a DnaA-initiation hyperstructure forms. Subsequent DNA replication and cell division generate different daughter cells containing different hyperstructures. This has the advantage of increasing the phenotypic diversity of the population. In developing this model, we also invoke hyperstructures in the partitioning of origins of replication.

Bacterial Proteins↗

PubMed2002

Quasi-periodic behaviour in a model for the lithium-induced, electrical oscillations of frog skin.

The fact that oscillations can be induced in studies of the maintenance of the electrical potential of frog skin by addition of lithium allowed evaluation of several parameters fundamental to the functioning of the system in vivo (e.g. relative volumes of internal compartments, characteristic times of ionic exchanges between compartments). A realistic model was thus proposed under the form of a set of ordinary differential equations. In the past, numerical simulations using such a model reproduced the periodic experimental oscillations and was able to provide an explanation for the global synchronised oscillations of the whole skin. In that paper, new numerical simulations reproduce the non-periodic oscillations which were observed two decades ago, but not reproduced by the model. Moreover, the dynamical process under which all the local oscillators are synchronised is explained in terms of a tangent bifurcation.

Adaptation, Physiological↗

PubMed2002

Hyperstructures, genome analysis and I-cells.

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology.

Algorithms↗