Working out how a cell responds to events is incredibly difficult. In general, cells change the expression of genes in response to signals such as how much food there is or changes in temperature. But the effects on gene expression are complex and, without better models, difficult to predict.
Working at the Weizmann Institute of Science, Shai Kaplan, Anat Bren and others worked out a way of mapping how a set of 20 genes in e coli cells react to changes in sugar levels. E coli is able to use several different sugars as sources of carbon:
"Each sugar system includes transporters that pump the sugar into the cell and enzymes that break it down. Each system also includes a transcription factor that senses the presence of the sugar and accordingly regulates gene expression. In addition, most of the sugar systems are regulated by a master transcription factor called CRP, which senses the starvation of the cell. This master regulator is activated by cAMP, a small molecule produced in the cell upon glucose starvation."
In principle, the sugar genes in the regulatory network should behave in a similar way: their expression should increase with the availability of a given sugar and, according to conventional wisdom, glucose starvation. So, it should be possible to model the system as a set of logic AND gates. But, one study of the lactose-input system showed a more complex logic function: a mixture of an AND and an OR.
Kaplan and colleagues used reporter strains of e coli that fluoresce green based on the level of expression of each sugar gene. They grew the cells in 96-well plates, making it possible to measure 96 different combinations of two input signals: eight levels of cAMP, to register the starvation signal, and twelve levels of the sugar to be measured. Using a robot, they measured the fluorescence at eight minute intervals over a twenty-hour period.
"We...find that most of the input functions show separation of variables, in the sense that they can be described as the product of simple functions that depend only on a single input."
That's the good news. Some functions hit a maximum as the level of a sugar rises, only to slip back down again as the level increases further. This was the case for galactose, but that may be because that sugar can be used as both a carbon source and a component of the cell wall. Some of the response combinations are far more complex than those where the variables can be separated.
"Even promoters in the same system can show different input functions, despite the fact that they are controlled by the same signals and regulators."
The question is: do the shapes of the different input functions depend on the structure of the individual promoters — the interactions between promoters, transcription factors and the cell environment can be complex — or the structure of the upstream circuitry, such as the cell's control loops?
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