Our model includes the two main glucose control mechanisms of catabolite repression and inducer exclusion. We show that this Boolean model is capable of predicting the ON and OFF steady states and bistability. Further, we present a reduced model which shows that lac mRNA and lactose form the core of the lac operon, and that this reduced model exhibits the same dynamics. Crowther Audrey audrey.crowther@huskers.unl.edu University of Nebraska-Lincoln 2016-11-08T10:38:26Z 2016-12-19T15:58:31Z

extracellular lactose at high concentrations

 2016-12-19T15:55:57Z

extracellular glucose

 2016-11-16T11:13:28Z

extracellular lactose at medium concentrations

 2016-12-19T15:56:16Z

lac mRNA

 2016-11-16T09:37:30Z

internal lactose in medium levels

 2016-12-19T15:56:16Z

allolactose at medium concentrations

 2016-11-16T10:27:22Z

internal lactose at high concentrations

 2016-12-19T15:55:57Z

allolactose at high concentrations

 2016-11-16T10:05:24Z

lac b-galactosidase

Gene Name: lacZ

UniProt ID: P00722

Gene ID: 945006

 2016-11-16T09:58:27Z

lac permease

Gene: lacY

UniProt ID: P02920

Gene ID: ID: 949083

 2016-12-19T15:56:16Z

lac operon repressor protein at medium concentrations

Gene Name: lacI

UniProt ID: P03023

Gene ID: 945007

 2016-11-16T10:56:42Z

Gene Name: lacI

lac operon repressor protein at high concentrations

UniProt ID: P03023

Gene ID: 945007

 2016-11-16T09:55:23Z

CAP (also known as CRP: cAMP receptor protein)

Gene Name: crp

UniProt ID: P0ACJ8

Gene ID: 947867

 2016-11-16T09:54:05Z

The lac repressor, at high and medium levels, inhibits transcription of the lac operon.

CAP upregulates lac mRNA expression.

The lac operon repressor inhibits lac mRNA formation.

CAP is the activator protein for the lac operon and is needed to form lac mRNA.

 S_13 1 S_10 1 S_12 1

Lac permease, with the presence of extracellular lactose at a medium concentration, leads to the presence of internal lactose.

The presence of extracelllular glucose inhibits the uptake of lactose into the cell.

Extracellular lactose at a high concentration is able to enter the cell via diffusion or through the basal value of permeases in the cell membrane (not modeled).

Extracellular lactose at a high concentration is able to enter the cell via diffusion or through the basal value of permeases in the cell membrane (not modeled).

Lac permease, with the presence of extracellular lactose at a medium concentration, leads to the presence of internal lactose.

Lac permease, with the presence of extracellular lactose at a medium concentration, leads to the presence of internal lactose.

The presence of extracelllular glucose inhibits the uptake of lactose into the cell.

 S_7 1 S_8 1 S_11 1 S_9 1 S_8 1

Internal lactose, at medium or high concentrations, is needed for the formation of allolactose. The conversion of lactose to allolactose is being preformed by a basal level of beta-galactosidase proteins, not shown in this model.

Internal lactose, at medium or high concentrations, is needed for the formation of allolactose. The conversion of lactose to allolactose is being preformed by a basal level of beta-galactosidase proteins, not shown in this model.

Internal lactose, at medium or high concentrations, is needed for the formation of allolactose. The conversion of lactose to allolactose is being preformed by a basal level of beta-galactosidase proteins, not shown in this model.

 S_2 1 S_4 1

The presence of extracellular glucose inhibits the uptake of lactose into the cell.

Lac permease, with the presence of extracellular lactose, leads to the presence of internal lactose.

Extracellular lactose must be present in order for lac permease to transport lactose into the cell.

lac permease is a membrane-bound protein whose function is to transport extracellular lactose into the cell.

The presence of extracelllular glucose inhibits the uptake of lactose into the cell.

 S_7 1 S_9 1 S_8 1

Internal lactose combined with beta-galactosidase produces allolactose.

Beta-galactosidase hydrolyzes lactose into glucose and galactose. In a separate reaction, beta-galactosidase also converts lactose into allolactose.

Beta-galactosidase hydrolyzes lactose into glucose and galactose. In a separate reaction, beta-galactosidase also converts lactose into allolactose.

 S_4 1 S_6 1

Translation of the lac mRNA later gives rise to b-galactosidase.

Translation of the lac mRNA gives rise to b-galactosidase.

 S_1 1

Translation of the lac mRNA later gives rise to lac permease.

Translation of the lac mRNA later gives rise to lac permease.

 S_1 1

The lac repressor is active at least at medium levels unless inhibited by allolactose (at high and medium concentrations) or if the lac repressor is already on.

The lac repressor is active unless inhibited by allolactose (at high and medium concentrations).

If the lac repressor is already active, then it will automatically be at least at a medium concentration.

The lac repressor is active unless inhibited by allolactose (at high and medium concentrations).

 S_12 1 S_3 1 S_12 1 S_5 1

The lac repressor is active unless inhibited by allolactose (at high and medium concentrations).

The lac repressor is inhibited by allolactose.

The lac repressor is inhibited by allolactose.

 S_5 1 S_3 1

Extracellular glucose prevents the formation of CAP.

In the absencse of extracellular glucose, CAP forms a complex with cAMP and binds to a site upstream of the lac promoter. Binding of the CAP-cAMP complex induces a conformational change that permits higher receptivity for mRNA polymerase.

 S_8 1