Wednesday, April 27, 2016

April 27, 2016 at 11:28PM

Today I Learned: 1) ...how cells maintain nonzero finite steady-state populations! Well, at least how T-cells do it, at least according to a simplified model. For all of y'all who guess they were secreting some kind of inhibiting factor into their environment... close! Feedback *is* implemented by excreting something, in this case IL-2 (interleukin-2, a protein). Critically, though, IL-2 doesn't just inhibit cell growth -- it also activates cell growth. More specifically, IL-2 triggers cell death in a linear fashion (cell death ~ IL-2 * k, k is some constant) and enhances growth cooperatively, which is a fancy way of saying that the growth rate of cells against concentration of IL-2 looks something like this: http://ift.tt/1rjuv5X. This combination of feedbacks gives the population two steady states, one at no cells and one at some finite amount of cells*. The fact that IL-2 mediates *both* cell death and cell growth is critical! If it just modified one or the other, or if it modified both in a linear fashion, you would not get a non-zero steady state (you can try something similar to what I describe below to show this). Interestingly, there's reason to expect cells to only use one growth factor instead of two. You *can* get the same behavior with two growth factors, but if you use two growth factors, the system is more sensitive to parameters like production rate of the growth factors. * To see why, draw a plot of cell death vs IL-2 concentration and cell growth vs IL-2 concentration on the same plot. Remember that cell death is linearly dependent on IL-2 concentration, while cell growth is sigmoidal with IL-2 concentration. Now pick a "current" cell concentration, which should be proxied well by IL-2 concentration. This is a location on the x-axis. If cell death is higher than cell growth, then the cells are net dying out, and the population moves left, towards zero. If cell growth is higher than cell death, then the cells are net growing, and the population moves right, towards cancer. Anywhere that cell growth and cell death are equal, you have a steady state population that doesn't move. You should find three steady states -- two that populations will move towards, and one that populations move away from. 2) It takes about 25 minutes for a relatively normal-sized ice cube to melt on a plate, outside, in shade, on a relatively warm day. That's a lot longer than I expected! Thanks to Dawna Bagherian for donating an ice cube! 3) The promoter on the ColE1 origin of replication that produces RNAII (which is what primes the plasmid for replication) can be replaced by other, standard promoters, and the plasmid replicates just fine.

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