Team:Amsterdam/project/diary/modelling

July 31st - Stochastic model of the Lac operon

We are using a glucose-insensitive lac operon to control the expression of our Zinc-Finger-methyltransferase fusion protein (FP), by replacing the three naturally controlled genes (LacY, LacZ and LacA) with our fusion protein. The signal to be registered in our proof of principle, lactose, controls the expression this operon. The lac operon has been extensively studied in the past fifty years and is known to display some 'leaky' expression of the three genes. This means that some operon expression will occur independent of the presence of the natural inducer lactose. How will this affect our project? Will the small amounts of fusion protein due to leaky expression cause all the bits in our Cellular Log to be methylated? Or is the leaky expression too low and/or are the diffusion and methylation times of the FP too high to form a serious threat?

To answer these questions, we decided it would be valuable to model the behaviour of the lac operon in a stochastic manner. Only this way, the activity of the low copies of FP can be accurately accounted for. Performing and analyzing stochastic simulations are more challenging than setting up a system of differential equations, expect to see some tips on this we have gathered 'the hard way' shortly! As a starting point, the stochastic model for the lac operon by <a href="http://www.ncbi.nlm.nih.gov/pubmed/19186128">Stamatikis & Mantzaris (2007)</a> has been replicated along with parameter values they have gathered. Although there are no \(k_{cat}\) values available for the methyltransferase that we use, M.ScaI, our gut feeling is that <p>