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.
Sunday, March 15, 2015
SysBio15 Asgn_20A_Class_20_Article_16_2015_03_19
Cellular Noise: Read Article 16 G. Lahav, N. Rosenfeld, A. Sigal, N.
Geva-Zatorsky, A. J. Levine, M. B. Elowitz, and U. Alon. Dynamics of the
p53-Mdm2 feedback loop in individual cells. Nat.Genet. 36 (2):147-150,
2004.. This is a very appealing paper, but not quite right. Post a PCRC.
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Juan Gnecco
ReplyDeleteAsgn20A
0 knew: the regulation of P53 according to DNA damage and little about its regulation with Mdm2. limitation to western blots
1 learned: the cyclical "pulse" regulation of p53 within one cell.the stochastic nature of each cell is different. the signal is digital: as in the number of pulses changed not the signal response
Pressing: are we getting too lost into the variability between cells? Its interesting but isnt the big picture (cumulative response) more important? Is there a similar series of oscillations during epigenetic programing?
Presentation: The patterns of gene regulation of indiviudal cells show a different method of regulation within individual cells
Thoughts: Could this be due to noise? and Very reminiscent of buzzer and sniffers
Tim Lee
ReplyDeleteAsgn_20A
0. Knew: P53 is a major tumor suppressing protein and has been studied thoroughly.
1. Learned: P53 regulation is not a simple negative feedback loop. P53 regulation involves pulses that eventually create damped oscillatory behavior. The idea of an analog response as opposed to a digital response.
2. Pressing: When it comes to analyzing individual cells, couldn't intrinsic noise play a huge factor in understanding the response in both timing and magnitude?
3. Presentation: Analyzing p53 regulation mechanism using immunoblots, irradiation, and fluorescence.
4. Thoughts: It's hard to read this and know in the back of my mind that something is not quite right with the paper.
Cameron Togrye
ReplyDeleteAsgn_20A
0.Knew: That P53 mutations function in the vast majority of cancer cases.
1. Learned: That in response to cell damage (via subjection to gamma rays), individual cells exhibit digital oscillatory responses of P53 whereby higher input signals produce higher number of same intensity, same width P53 peaks.
2. How many other phenomenon are actually the aggregate result of "noisy" individual cell responses? Also, is there are direct correlation between number of pulses and amount of DNA damaage? Is there a certain point where the cell "gives up"?
3. Presentation: The anti-DNA damage proteins that P53 upregulates
4. Thoughts: Is this really a paper about "noise" per se? Exposure to gamma rays doesn't affect every cell the same way (as interaction with DNA is in some ways a statistical effect). Thus these varying digital signals represent this, and the signals themselves aren't random fluctuations.
Zach Bednarke
ReplyDeleteasgn 20a
0- I really didnt know much since the article focuses on a specific protein mechanism
1- DNA damage is related (not specified if proportional or not) to the amount of P53 released, meaning that the cell's mechanism for dealing with gentic damage can quanitify how much occured. Also, I found the concept of a digital periodic release fascinating- it deserves to be in the sniffers and buzzers paper.
2- Id like to know the function that determines the total amount of p53 pulses. What exactly does p53 do?
3- biological clocks
4- Reading Cam's post, I realize he's got a good point. The big point of this paper seems to be the digital form of the p53 mechanism- not the fact that the "noise" of genetic damage is being dealt with, or how it is dealt with. I don't mind it being lumped in, but why didnt we talk about it during sniffers and buzzers?
James Pino
ReplyDeleteAsgn_20A
0:Knew: P53s function as a goalie who can lead to destruction of the cell
1:Learned: The "priming" of p53 via oscillations of p53 induced by mdm2. Use of experimental methods to monitor single cell oscillations of key proteins.
2:pressing: When the cell is images is there any loss of fluorescence due to how it adheres to the plate? Are there any other methods to monitor single cells over time not by imaging?
3:Presentation: Methods for single cell single molecule studies
4:Thoughts: I like how the priming works.I wonder where the cells do die within the oscillation?