Search PubMed⌕ Search

Biomedical subjects

Frank Bruggeman

Publications and source records attributed to Frank Bruggeman.

5 recordsLinked to original sources
PubMed2005

Towards building the silicon cell: a modular approach.

Systems Biology aims to understand quantitatively how properties of biological systems can be understood as functions of the characteristics of, and interactions between their macromolecular components. Whereas, traditional biochemistry focused on isolation and characterization of cellular components, the challenge for Systems Biology lies in integration of this knowledge and the knowledge about molecular interactions. Computer models play an important role in this integration. We here discuss an approach with which we aim to link kinetic models on small parts of metabolism together, so as to form detailed kinetic models of larger chunks of metabolism, and ultimately of the entire living cell. Specifically, we will discuss techniques that can be used to model a sub-network in isolation of a larger network of which it is a part, while still maintaining the dynamics of the larger complete network. We will start by outlining the JWS online system, the silicon cell project, and the type of models we propose. JWS online is a model repository, which can be used for the storage, simulation and analysis of kinetic models. We advocate to integrate a top-down approach, where measurements on the complete system are used to derive fluxes in a detailed structural model, with a bottom-up approach, consisting of the integration of molecular mechanism-based detailed kinetic models into the structural model.

Animals↗
PubMed2002

A turbo engine with automatic transmission? How to marry chemicomotion to the subtleties and robustness of life.

Most genomes are much more complex than required for the minimum chemistry of life. Evolution has selected sophistication more than life itself. Could this also apply to bioenergetics? We first examine mechanisms through which bioenergetics could deliver sophistication. We illustrate possible benefits of the turbo-charging of catabolic pathways, of loose coupling, low-gear catabolism, automatic transmission in energy coupling, and of homeostasis. Mechanisms for such phenomena may reside at the level of individual proton pumps, or consist of rerouting of electrons over parallel pathways. The mechanisms may be confined to preexisting components, or involve the plasticity of gene expression that is so characteristic of most living organisms. These possible benefits lead us to the conjecture that also bioenergetics has evolved more for sophistication than for necessity. We next discuss a hitherto unresolved enigma, i.e. that bioenergetics does not seem to be critical for the physiological state. To decide on how critical bioenergetics is, we quantified the control exerted by catabolism on important physiological functions such as growth rate and growth yield. We also determined whether a growth inhibition mostly affected bioenergetics (catabolism) or anabolism; if ATP increases with growth rate, then growth should be considered energy (catabolism) limited. The experimental results for Escherichia coli pinpoint the enigma: its energy metabolism (catabolism) is not critical for growth rate. These results might suggest that because it has no direct control over cell function, bioenergetics is unimportant. Paradoxically however, in biology, highly important mechanisms tend to have little control on cell function, precisely because of that importance. Sophistication in terms of homeostatic mechanisms has evolved to guarantee robustness of the most important functions: The most important mechanisms are redundant in biology. Bioenergetics may be an excellent example of this paradox, in line with the above conjecture. It may be highly important and sophisticated. We then discuss work that has begun to focus on the sophistication of bioenergetics. Homeostasis of the energetics of DNA structure in E. coli is extensive. It relies both on preexisting components and on responsive gene expression. The vastly parallel electron-transfer network of Paracoccus denitrificans engages in sophisticated dynamic and hierarchical regulation. The growth yield of the organism can depend on which terminal oxidases are active. Effective proton translocation may vary due to rerouting of electrons. We conclude that much sophistication of bioenergetics will be discovered in this era of functional genomics.

Adenosine Triphosphate↗
PubMed2002

ECA: control in ecosystems.

Although metabolic control analysis (MCA) cannot be applied directly to microbial ecological systems because of mass conservation and stoichiometric constraints, we demonstrate here that Hierarchical Control Analysis (HCA) can be applied to such systems. We illustrate the approach for a particular ecosystem example of the biological synthesis of acetic acid from glucose, and uncover some surprising aspects to the control of this miniature ecosystem.

Acetic Acid↗