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.
Arman Chowdhury
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0. Knew: Intracellular processes and signal propagation across a cell is regulated by spatio-temporal coupling of signaling activities.
1. Learned: Signalling specificity does not depend on a single protein or gene for an individual receptor pathway; rather, specificity is determined by the temporal and spatial dynamics of downstream signaling components. Negative feedback provides robustness to noise; positive feedback greatly increases sensitivity to signal and might also lead to bistabilty and relaxation oscillations. Hysteresis is a hallmark of bistabiltiy. Spatial segregation of two opposing enzymes (in a protein modification cycle) can generate intracellular gradients.
2. Pressing: The article talks about kinases forming a supra-molecular structure during spatial segregation of opposing enzymes (Fig 3). What triggers the formation and degradation of these multi-molecular structures? Is the process strictly cyclical in time?
3. Presentation: Neat organization of paper: mechanistic modelling, challenges of mechanistic modelling, temporal modelling, spatial modelling, spatio-temporal modelling. Good visual representations of modelling, and okay explanation of differential equations.
4. Thoughts: This article seems more relevant to systems biology than the previous paper we read. However, I wish they had talked a little more about facilitated communication within cells, and explained the differential equations a bit better.
Cameron Togrye
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0. Knew: MAPK function in regulating transcription factors and was activated as part of both the GPCR and RTK systems. Was also aware of the mechanisms of both RTK and GPCR general activation.
1. Learned: Scaffold proteins (or other shuttle proteins) are necessary for the transmission of information via protein kinases when distances grow to more than a few micrometers.
2. Pressing: Why does the localization of catalyst like SOS experience a 10^2-10^3 increase in affinity for Ras-GDP when they are concentrated into a small. How does proximity to each other increase the affinity of these enzymes for their substrate? Are the enzymes interacting?
3. Presentation: Various methods of protein localization the cell
4. Thoughts: I think the unforseen complexity of pathways that I learned in other classes is interesting. I had no idea, for example, that the EGF-Shc-Ras pathway had so many different combinations of binding and pathways. What I learned in Cell Bio suddenly seems profoundly oversimplified.
Tim Lee
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0. Knew: Cell signaling pathways depend on spatio-temporal aspects and can have a major influence on regulation and outputs.
1. Learned: How temporal regulation can affect protein output behavior. Different types of fundamental temporal cell signaling regulation leading to different kinds of oscillations and bistable positions. How spatial regulation can determine signalling outputs. Spatial gradients of kinases and phosphatases create a variety of concentrations throughout the cell.
2. Pressing: How are the kinase and phosphatase gradients established in a cell?
3. Presentation: Spatio-temporal regulation of cell signalling.
4. Thoughts: It was interesting and helpful that the article constantly paired new concepts of cell signaling with ordinary differential equations.
Cami Johnson
ReplyDeleteAssignment 24A
0. Knew: The role of tyrosine kinase receptors in cell signaling and the importance of spatiotemporal activation
1. Learned: That the same signaling proteins can result in drastically different responses depending on the spatial and temporal activation profiles
2. Pressing ?: With the combinatorics involved, how difficult is this to model?
3. Presentation: spatiotemporal profiles of certain signaling cascades
4. Thoughts: This really helped me understand the importance of spatio-temporal profiles, and particularly the rationale behind wanting a spatio-temporal illustration for RTA.