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
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Ayeeshik Kole
ReplyDeleteAsgn_18/p53 Oscillator
0. Knew: I knew p53 was a tumor suppressor.
1. Learned: p53 shows asynchronous pulses when exposed to non-stressors, whereas there are synchronized pulses due to damage. Cell-cycle arrest, apoptotic, and repair activities only occur after damage due to a switch like mechanism that can distinguish between transient and sustained accumulation of p53.
2. Pressing ?: Can the modification of p53 that changes it between active and non-active be thought of as an integrator circuit element? Can the threshold before accumulation of p53 be lowered?
3. Presentation: p53 in cancer
4. Thoughts: Article was very well written, with a logical flow. They made no broad assumptions and consolidated what seems like many years of work into a few pages. Figures and biochemistry was tough to follow for me though, but did not really take away from it.
Erica Curtis
ReplyDeleteAsgn_18/p53 Oscillator
0. Knew: p53 is a tumor suppressor that can result in cell arrest or apoptosis.
1. Learned: p53 signaling must be significantly sensitive to not result in unwanted cell death when sensing acceptable cell damage during normal growth. At a basal levels and under normal DNA stress levels, cells exhibit spontaneous undamped pulses of p53 of fixed and comparable amplitude and duration that seem to be independent of cell damage sustained. At the basal level the pulses are asynchronous; after DNA damage, the pulses are synchronized. Sustained damage results in p53 posttranslational modifications that induce the full p53 response. p53 that has not been posttranslationally modified is insufficient to activate p21, a mediator of cell cycle arrest.
2. Pressing ?: The authors refer to the C-terminal modifications of p53 as a “switching mechanism”. Is that the best analogy? And would it be a toggle or one-way switch?
3. Presentation: Clinical Applications of p53
4. Thoughts: I appreciated the stress at the end of the paper on the overall importance of studying single-cell basal levels of expression to establish a baseline.
Lucas Hofmeister
ReplyDeleteAsgn_18/p53
0. Knew: the p53 Pathway is dysregulated in almost all human cancers
1. Learned: p53 Activity is uncoupled from is transcriptional activity (accumulation)
2. Pressing ?: What kind of toggle is C-terminal modification of p53? Also, Im very curious about the times scales involved. they briefly mention it but dont go into much detail.
3. Presentation: Methods of live cell imaging
4. Thoughts: I really like this paper. the experimental design is impressive and i think they chose a great reductionist strategy for the study. The major limitation that i see is that their readout was mostly based on the canonical pathway (p21 activation), however, they recognize this and cite some alternatives.This is a VERY intimidating paper!
Also, the point that investigating the basal dynamics is just as important as the dynamics under stress or disease conditions is very interesting. It begs a huge question though -- how can we change the paradigm of research to facilitate these types of studies? It seems like we always study the disease mechanism first and then get around to the "normal" if we think that we need to.
Will Matloff
ReplyDelete18/p53
0. Knew: p53 is an important in cell repair to damage.
1. Learned: The dynamics of p53 allow for it to have both high sensitivity and allow for tolerance to normal damage.
2. Pressing? How does post-translational modification work and how is it controlled?
3. Presentation: Mechanisms for cell repair.
4. Thoughts: This was a very nice paper. It shows how the concepts of dynamics can be better used to understand biology.
Zach Eagleton
ReplyDeleteAsgn_18/p53 Oscillator(2010)
0 Knew: Basics from the 04 paper.
1 Learned: Spontaneous pulses are causally related to events in the cell cycle. The DSB kinases are primarily responsible for the p53 pulses. The mechanism is highly sensitive. Uses C-terminal modifications to distinguish transient damage from sustained damage.
2 Pressing ?: Is there any grey area in transient vs sustained damage? If so how is this filtered?
3 Presentation: Single cell vs. population level dynamics
4 Thoughts: Though the article was well written and allowed the reader to get the main idea of the article without knowing a lot of biochemistry.
Brian Evans
ReplyDelete18/p53 oscillator
0. Knew: I knew p53 is upregulated in response to DNA damage and that its behavior constitutes a biochemical oscillator.
1. Learned: That the interplay between p53 and other damage activated kinases results in the full effect of p53 (i.e. p21 activation) by acetylation/demethylation of the p53 c-terminus. I also learned that p53 is spontaneously expressed in all cells as a natural checkpoint during the cell cycle, although it remains inactive as only sustained DNA damage can result in sustained co-activation of the kinases necessary for post-translational modification of p53 into its active form.
2. Pressing ?: Can we exogenously mediate post-translational modification of p53 to its active form? (Could be a potential chemotherapeutic...)
3. Presentation: Post-translational modification of p53
4. Thoughts: I learned a lot from this paper, and I appreciate the attention to detail balanced by the easily understood text. I wish more scientific papers were written in this style as opposed to verbose grandiosity.