Biomedical subjects

René Thomas

Publications and source records attributed to René Thomas.

4 recordsLinked to original sources

PubMed2003

The formation of sense organs in Drosophila: a logical approach.

The genetic analysis of development has revealed the importance of small sets of interacting genes in most morphogenetic processes. The results of gene interactions have so far been examined intuitively. This approach is largely sufficient when one deals with simple interactions, a feedback circuit for example. As more components become involved, however, it is difficult to make sure that the intuitive approach gives a comprehensive view of the behaviour of the system. In this paper, we illustrate the use of a logical approach to describe the genetic circuit that underlies the singling out of sense organ precursor cells in Drosophila. We show how to apply logical modelling to a realistic problem, and how this approach allows an easy assessment of the dynamic properties of the system, i.e., of its possible evolutions and of its reactions to fluctuations and perturbations.

Animals↗

PubMed2003

Emergence of complex behaviour from simple circuit structures.

The set of (feedback) circuits of a complex system is the machinery that allows the system to be aware of the levels of its crucial constituents. Circuits can be identified without ambiguity from the elements of the Jacobian matrix of the system. There are two types of circuits: positive if they comprise an even number of negative interactions, negative if this number is odd. The two types of circuits play deeply different roles: negative circuits are required for homeostasis, with or without oscillations, positive circuits are required for multistationarity, and hence, in biology, for differentiation and memory. In non-linear systems, a circuit can positive or negative (an 'ambiguous circuit', depending on the location in phase space. Full circuits are those circuits (or unions of disjoint circuits) that imply all the variables of the system. There is a tight relation between circuits and steady states. Each full circuit, if isolated, generates steady state(s) whose nature (eigenvalues) is determined by the structure of the circuit. Multistationarity requires the presence of at least two full circuits of opposite Eisenfeld signs, or else, an ambiguous circuit. We show how a significant part of the dynamical behaviour of a system can be predicted by a mere examination of its Jacobian matrix. We also show how extremely complex dynamics can be generated by such simple logical structures as a single (full and ambiguous) circuit.

Feedback↗

PubMed2003

Hardware (DNA) circuits.

A scheme is presented whereby a new genetic control circuit can be introduced into an organism, permitting the experimenter to turn the expression of a given gene (or set of genes) on or off at will. The proposed scheme involves a positive feedback loop--here, a positive regulator, the CII protein of phage lambda, with its structural gene engineered so as to require CII for its expression. This feedback loop creates the possibility of two stable steady states, with gene cII ON or OFF. Genes added downstream of cII and lacking a promoter will follow the same expression as cII. Two additional circuits allow the experimenter to switch at will between the ON and OFF states.

Bacteriophage lambda↗

PubMed2002

Conceptual tools for the integration of data.

We propose to start the analysis of complex systems by systematically identifying the feedback circuits that govern their dynamics. These circuits can be identified without any ambiguity by examining the Jacobian matrix of the system. They provide precious information regarding the number and nature of steady states. Logical descriptions use variables and functions that can take only a limited number of discrete values (in simple cases, only two, 0 or 1). We developed an asynchronous method with continuous time, generalized by using variables with more than two levels and logical parameters. Reverse logics is a synthetic, inductive method. It aims at proceeding rationally from the experimental facts towards models rather than from models to predictions.

Animals↗