PubMed Health⌕ Search

Biomedical subjects

T S Gardner

Publications and source records attributed to T S Gardner.

4 recordsLinked to original sources
PubMed2004

Robust identification of large genetic networks.

Temporal and spatial gene expression, together with the concentration of proteins and metabolites, is tightly controlled in the cell. This is possible thanks to complex regulatory networks between these different elements. The identification of these networks would be extremely valuable. We developed a novel algorithm to identify a large genetic network, as a set of linear differential equations, starting from measurements of gene expression at steady state following transcriptional perturbations. Experimentally, it is possible to overexpress each of the genes in the network using an episomal expression plasmid and measure the change in mRNA concentration of all the genes, following the perturbation. Computationally, we reduced the identification problem to a multiple linear regression, assuming that the network is sparse. We implemented a heuristic search method in order to apply the algorithm to large networks. The algorithm can correctly identify the network, even in the presence of large noise in the data, and can be used to predict the genes that directly mediate the action of a compound. Our novel approach is experimentally feasible and it is readily applicable to large genetic networks.

Algorithms↗
PubMed2000

Construction of a genetic toggle switch in Escherichia coli.

It has been proposed' that gene-regulatory circuits with virtually any desired property can be constructed from networks of simple regulatory elements. These properties, which include multistability and oscillations, have been found in specialized gene circuits such as the bacteriophage lambda switch and the Cyanobacteria circadian oscillator. However, these behaviours have not been demonstrated in networks of non-specialized regulatory components. Here we present the construction of a genetic toggle switch-a synthetic, bistable gene-regulatory network-in Escherichia coli and provide a simple theory that predicts the conditions necessary for bistability. The toggle is constructed from any two repressible promoters arranged in a mutually inhibitory network. It is flipped between stable states using transient chemical or thermal induction and exhibits a nearly ideal switching threshold. As a practical device, the toggle switch forms a synthetic, addressable cellular memory unit and has implications for biotechnology, biocomputing and gene therapy.

Bacterial Proteins↗
PubMed1998

A theory for controlling cell cycle dynamics using a reversibly binding inhibitor.

We demonstrate, by using mathematical modeling of cell division cycle (CDC) dynamics, a potential mechanism for precisely controlling the frequency of cell division and regulating the size of a dividing cell. Control of the cell cycle is achieved by artificially expressing a protein that reversibly binds and inactivates any one of the CDC proteins. In the simplest case, such as the checkpoint-free situation encountered in early amphibian embryos, the frequency of CDC oscillations can be increased or decreased by regulating the rate of synthesis, the binding rate, or the equilibrium constant of the binding protein. In a more complex model of cell division, where size-control checkpoints are included, we show that the same reversible binding reaction can alter the mean cell mass in a continuously dividing cell. Because this control scheme is general and requires only the expression of a single protein, it provides a practical means for tuning the characteristics of the cell cycle in vivo.

Animals↗