The Systems Biology of COVID-19 and the SARS-CoV-2 virus. The class will build a foundation that includes the emergence of complexity, simple biological subsystems, their reductionist and equivalent toy and organ-chip models, and the measurements required to specify model architecture and parameters. Applications to biology, physiology, medicine, chemical and biological defense, pharmacology, drug discovery, and toxicology. UGrad: PHYS 240 01 and BME 290B; Grad: PHYS 326 and BME 395C.
Tuesday, March 13, 2012
Asgn_19_Class_24_Article_17_2012_03_14
Read Article 17: Lahav,G, Rosenfeld,N, Sigal,A, Geva-Zatorsky,N, Levine,AJ, Elowitz,MB, Alon,U. Dynamics of the P53-Mdm2 Feedback Loop in Individual Cells, Nat.Genet., 36, 147-150, 2004. This is the first paper in the series. Try to figure out what was learned between 2004 and 2010. Post a PCRC.
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Ayeeshik Kole
ReplyDeleteAsgn_19/p53 Oscillator (2004)
0. Knew: I read the 2010 article before this article, so I was already knew how the p53-tale ended.
1. Learned: p53-Mdm2 feedback loop creates pulses that act as a digital 'clock' counting down until p53 action is exhibited
2. Pressing ?: They mention checkpoints to check for damage. Does p53 just take advantage of the intrinsic cell-cycle checkpoints for damage?
3. Presentation: Timeline of discovery
4. Thoughts: It was interesting to see Lahav go from first author to last author during this tale of p53 oscillations. The biggest discovery, I think, were the study of basal levels of p53 and also that p53 pulses were tied to the cell-cycle.
Erica Curtis
ReplyDeleteAsgn_19/p53 Oscillator (2004)
0. 2004→2010: They seemed to learn in this gap that at the basal level the pulses are asynchronous while after DNA damage, the pulses are synchronized. They also learned of the importance of posttranslational modifications with sustained damage in activating p21.
1. Learned: The p53-Mdm2 negative feedback loop forms a digital clock that provides robustness to the p53 response.
2. Pressing ?: How does this clock work if all signals are of similar amplitude and duration?
3. Presentation: Other Examples of Digital Clocks
4. Thoughts: The paper was not as clearly written as the 2010 paper.
Zach Eagleton
ReplyDeleteAsgn_19/p53 Oscillator(2004)
0 Knew: That p53 is a tumor suppressor that displays oscillator behavior.
1 Learned: That the p53-Mdm2 negative feedback loop displays digital pulses rather than graded analog responses.
2 Pressing ?: How does positive feedback enhance oscillatory behavior?
3 Presentation: Circadian Rhythms
4 Thoughts: I read this paper first and it seems as if a lot has been learned between '04 and '10.
Lucas Hofmeister
ReplyDeleteAsgn_19/p53
0. Knew: population studies led to big misconceptions about how this regulatory pathway works
1. Learned: This system acts like a digital feedback loop (i just didnt pick up on that in the 2010 paper)
2. Pressing ?: This negative feedback loop is acting as a clocking mechanism, and the # of pulses is what is important for cell response...does this really mean that the frequency of pulses is most important? or is this the # of pulses during one cell cycle.
3. Presentation: Biological analog to digital converters
4. Thoughts: It is very interesting to read this paper after the 2010 paper. Again, i think it is very impressive how systematically they are approaching this problem.
Will Matloff
ReplyDelete19/p53
0. Knew: The dynamics of p53 from the 2010 paper.
1. Learned: The p53-Mdm2 feedback loop acts as an oscillator.
2. Pressing? What are the primary reasons for cells to have different dynamics at any given time, such that the average dynamics mask the individual dynamics?
3. Presentation: Network motifs.
4. Thoughts: A lot of work was done form this paper to the 2010 paper.
Brian Evans
ReplyDelete19/p53 and MDM2 feedback loop
0. Knew: that cell population studies obscure understanding of dynamic cellular signalling processes.
1. Learned: That the amplitude of a cellular response can be independent of the amplitude of the input. I also learned that a 'digital clock' is a means to make a system robust.
2. Pressing?: Are there other players in this feedback loop that are being overlooked?
3. Presentation: How to utilize dynamic cell responses to develop novel therapeutic interventions.
4. Thoughts: Hilton Head island kicks ass.