Galit Lahav and a negative-feedback loop
[This post is heavy on scientific details. I needed to prove to myself, and perhaps the researchers, that I could follow the science, at least to a degree. After this post I decided to focus the blog on things that resonated with me and my observations. Read or skip ahead as you are inclined.]
After a tour I spent some time talking to Galit Lahav about her research into the p53-mdm2 negative-feedback loop. She told me that p53 is one of the most studied proteins in the human body because of its role in cancer prevention. When it recognizes damage to the cell's DNA (found by other proteins), p53 starts a process that either fixes the DNA or kills the cell through something called apoptosis. We don't know how or why it makes a decision to fix or to kill, but people are trying to find out.
p53 is paired in a negative feedback loop with a protein called mdm2. When the amount of p53 goes up, the amount of mdm2 also goes up, but when the amount of mdm2 goes up, the amount of p53 goes down. Usually these types of oscillations either go on forever or get smaller and smaller until they disappear. This second type of behavior is called damped oscillation.
Biologists used to believe that the p53-mdm2 feedback loop was a damped oscillation. The experiments all seemed to show this, but they only looked at cell colonies. In other words, they measured the amount of each of these proteins over time in an entire colony of cells. These measurements showed a damped oscillation. In her post-graduate work, Galit measured the protein levels in individual cells and found that the loop oscillated a finite number of times with no reduction in amplitude. In other words, the levels of p53 and msm2 went up and down once, twice, three times or more and then stopped. No damping.
In her lab at SB they are trying to understand why the oscillation works this way. They develop theoretical models and then test them in the lab. Systems Biology seems to be about combining these two parts of biology: theoretical and experimental, or as those in the know say, dry work and wet work.
Galit showed me some movies of the cell proteins changing. To make the proteins visible under a microscope, scientists attach colored fluorescing proteins (CFP, cyan fluorescent protein, and YFP, yellow flourescent protein) to the p53 and mdm2. You could easily see the discreet oscillations. She also showed me beautiful movies of cells destroying themselves through apoptosis. They don't just fade away; they bubble and explode and form these bubbles called blebs (similar to my domain, blep!).
After a tour I spent some time talking to Galit Lahav about her research into the p53-mdm2 negative-feedback loop. She told me that p53 is one of the most studied proteins in the human body because of its role in cancer prevention. When it recognizes damage to the cell's DNA (found by other proteins), p53 starts a process that either fixes the DNA or kills the cell through something called apoptosis. We don't know how or why it makes a decision to fix or to kill, but people are trying to find out.
p53 is paired in a negative feedback loop with a protein called mdm2. When the amount of p53 goes up, the amount of mdm2 also goes up, but when the amount of mdm2 goes up, the amount of p53 goes down. Usually these types of oscillations either go on forever or get smaller and smaller until they disappear. This second type of behavior is called damped oscillation.
Biologists used to believe that the p53-mdm2 feedback loop was a damped oscillation. The experiments all seemed to show this, but they only looked at cell colonies. In other words, they measured the amount of each of these proteins over time in an entire colony of cells. These measurements showed a damped oscillation. In her post-graduate work, Galit measured the protein levels in individual cells and found that the loop oscillated a finite number of times with no reduction in amplitude. In other words, the levels of p53 and msm2 went up and down once, twice, three times or more and then stopped. No damping.
In her lab at SB they are trying to understand why the oscillation works this way. They develop theoretical models and then test them in the lab. Systems Biology seems to be about combining these two parts of biology: theoretical and experimental, or as those in the know say, dry work and wet work.
Galit showed me some movies of the cell proteins changing. To make the proteins visible under a microscope, scientists attach colored fluorescing proteins (CFP, cyan fluorescent protein, and YFP, yellow flourescent protein) to the p53 and mdm2. You could easily see the discreet oscillations. She also showed me beautiful movies of cells destroying themselves through apoptosis. They don't just fade away; they bubble and explode and form these bubbles called blebs (similar to my domain, blep!).
0 Comments:
Post a Comment
<< Home