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Abstract

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.

Regulation of <b><i>crp</i></b> Gene Expression by the Catabolite Repressor/Activator, Cra, in <b><i>Escherichia coli</i></b>

“…The details of this proposed regulatory mechanism are currently under investigation. It is anticipated that interrelated networks of regulatory interactions such as those described here will provide bacteria with mechanisms for fine-tuning and coordinating the different aspects of their metabolism and physiology (Amar et al, 2002; Babu and Teichmann, 2003). …”

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

“…In the pursuit of the nature of the bacterial cell, we and others have explored the possibility of the existence of a level of organisation intermediate between macromolecules and whole cells—the level of hyperstructures (Amar et al 2002; Guzman et al 2002; Molina and Skarstad 2004). A hyperstructure is a collection of diverse molecules (genes, mRNAs, proteins, ions, lipids) that is associated with at least one function.…”

Modélisation cellulaire pour l'émergence de structures multiprotéiques auto-organisées

“…Inversement, si on peut accéder aux propriétés individuelles des protéines, nous ne pouvons pas les analyser dans le contexte de la formation d'une structure cellulaire. C'est donc à l'interface entre ces deux niveaux, moléculaire d'un coté et structures cellulaires de l'autre, que la simulation peut apporter un gain substantiel (Amar et al, 2002). On notera cependant que le transfert de propriétés d'un niveau à l'autre est un processus dans lequel l'organisation spatiale revêt une importance prépondérante, aussi bien au niveau moléculaire (taille et conformation des molécules) qu'au niveau cellulaire (localisation et conformation des structures).…”

“…À partir de ce constat, nous proposons dans cet article un outil de simulation cellulaire, 3DSPI (3D Simulator of Protein Interactions), conforme à ce que nous estimons devoir être un modèle cellulaire en biologie des systèmes. Ce modèle est basé sur le formalisme multi-agents, que nous pensons -rejoignant en cela d'autres auteurs (Amar et al, 2002) -être le plus adapté. Nous dressons ici un tableau aussi complet que possible de la démarche suivie, depuis le projet scientifique jusqu'à l'implémentation.…”