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.
Frank "Edad" Block, Jr.
ReplyDeleteSysBio13 Asgn_12_Class_16_Article_20_2013_10_17
0: Knew: Prior Tyson papers.
1: Learned: Application of prior Tyson mechanisms to cell division. Seesaw example.
2: Pressing: The next stage up is the level of the organism rather than the cell. This paper gives examples of groups of cells - maybe even an organ - but how does the control of the whole organism growth (from single cell) and reproduction (back to single cell) work?
3: Presentation: Dynamics of organ growth and regulation; Dynamics of organism growth and regulation
4: Thoughts: We need to examine the extent to which "growth and regulation of the organ" (above) is applicable, or not applicable, to Organ on a Chip.
0. Knew: Previous Tyson; Cell Cycle regulation
ReplyDelete1. Learned: Cell Cycle in terms of toggle switches, amplifiers and oscillators. Bifurcation analysis of cyclin and Cdc2 activity.
2. Pressing: How are the regulatory mechanisms changed in cancerous cells? How would Tyson model cancerous escape from the cell cycle?
3. Presentation: Cell Cycle in gametes. How would Tyson model meiosis regulation? How would meiosis be incorporated on OoCs? Would they be able to reproduce?
4. Thoughts: I agree with Frank, we need to determine to what extent these control systems should operate in an OoC.
0. Understood the basics of oscillators from the previous Tyson readings and class discussion as well as I had a solid understanding of the cell cycle but did not know the kinases specific to yeasts.
ReplyDelete1. Using the cell mass to nucleus ratio and comparing it to the critical kinase levels is an interesting and useful mechanism to look at cell cycle regulation.
2. Can other cellular structures be used to plot against other enzyme / kinase activity in a cell to see regulation of other critical events? Glycolysis?
3. Possible presentation or report would be to explore other the dynamics of other cellular structures and the activity within that organelle.
4. This concept could have potential in terms of how to control the behavior in an OoC...seeing increased mass / nucleus indicates cellular proliferation so do we turn it up or slow it down in the OoC.
SysBio13 Asgn_12_Class_16_Article_20_2013_10_17
ReplyDelete0. Knew: information from previous Tyson papers, general steps of cell cycle
1. Learned: details of cell cycle regulation, how they can be described by bifurcation diagrams and how these can illuminate the way mutations alter the system
2. Questions: in order to create these bifurcation diagrams, are they making actual measurements (or finding them in literature) to populate the variables or are they general ideas that mimic what is going on in the cell?
3. Presentation:
4. Thoughts: interesting to see how the types of plots/systems he described in his other papers can be applied/found in actual cellular systems; can we apply this type of control to the cells in OoC...would we want cells to divide the point of carrying capacity or apply a different limit?
SysBio13 Asgn_12_Class_16_Article_20_2013_10_17
ReplyDelete0. Knew previous Tyson paper and basics of oscillators.
1. Learned examples of cellular oscillations, the cell cycle is certainly a great place to start looking at oscillations. Learned the basic control mechanisms of cell division.
2. Questions: Can we add more parts of the puzzle? What are we more limited by right now: lack of biological knowledge or computing complexity?
3. Presentation: Expanding the mathematical model
4. Thoughts: It was nice to see a more in depth look cell division control system from the previous paper
0 Knew: Basic cell cycle components and bifurcation basics
ReplyDelete1 Learned: How stable and unstable states define the different stages in a cell's division cycle and how the checkpoint mechanisms work.
2 Pressing: What happens when you add additional cells and cell-cell interactions... tissues? How do you combine these bifurcation diagrams?
3 Presentation: Predicting System Diagrams for Disease
4 Thoughts: I really enjoyed this paper. It addressed some of my remaining confusion about oscillations and bifurcations and answered a lot of my questions about the purpose of computer modeling. I also thought it was interesting that researches could accurately predict the performance of mutants using the models. But would this be possible with more complex diseases?
David Wooten
ReplyDeleteSysBio13 Asgn_12_Class_16_Article_20_2013_10_17
0.) Knew: Dynamical systems theory, previous lead-up to cell cycle bifurcation diagram
1.) Learned: How intercellular signalling might alter the shape of the bifurcation diagram, and thus one cell can exert control over the internal state of another.
2.) Pressing ?: What are equations governing organ interaction systems? Can similar bifurcation diagrams be made to analyze OoCs, and how organs interact (e.g. Pinnochio Effect?)
3.) Presentation: Mathematical models of organ interactions
4.) Thoughts: I enjoyed this paper, but I think the presented bifurcation diagrams were simpler looking than they really are. The stable (and unstable) steady states are really 1D lines through a very high dimensional space (they only plot Cdc2:Cdc13, but there are many other dimensions to the phase space). What we see is just a 2d projection of the high dimension trajectory, and in high dimensional spaces, things that we haven't had to talk about can happen. For instance, in Figure 3 imagine a cell was at mass/nucleus=2, and started with Cdc2:Cdc13 ~= 0.35 (between the orange dashed and green dashed curves. Where would it go? All it has are unstable steady states around it - and it is impossible to cross an unstable steady state, even to get to a stable one! Well, in 3 (or higher) dimensions, it's no problem - just go around the line.
This is a general problem with displaying data in higher than 2 dimensions, but it makes it very difficult to visually analyze a 2D projection of a high dimensional bifurcation diagram.
Also, it should be true that the stable M phase oscillations meet up with the unstable M phase oscillations somewhere, but it's never shown connecting up.
Overall, I think these diagrams make things look simpler than they may be in reality.