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.
0. I am well acquainted with DTRA and what the organization is looking for.
ReplyDelete1. The “open system” is critical in order to determine exposure CB agents. Most are liquids or aerosols and spread to target organs through the blood. I also found the specificity in the molecular and biochemical pathways listed interesting.
2. I think the most difficult part of development listed in the BAA is the “blood surrogate.” The surrogate needs to be a realistic as possible in order to accurately develop the MCM and see the MCM effect on the other systems.
3. The advantages of CB Agent in vitro models.
4. DTRA really needs to update their website....I have seen the same pictures on there since April.
Frank "Edad" Block, Jr.
ReplyDeleteSysBio13 Asgn_9D_Class_07_DTRA RFP__2013_09_17
0. Knew: DARPA & NIH.
1. Learned: Here, "teams." "Open system."
2. Pressing: Only 4 organs here. Why not 10 as in DARPA?
***Why do they want an "Open System" (page 4)? This would not seem to be the correct model AT ALL!! Or are they using the term in a novel way? (I interpret Open System to mean that the blood substitute is not recirculated.)
Blood substitute: Serum is not allowed (page 9). There MUST be some plasma oncotic agent (protein, complex starch, Dextran).
3. Presentation: How to detect toxicity in organ cultures.
4. Thoughts: Drugs and conditions that trigger Diffuse Intravascular Coagulation (DIC) will likely not be detected because there is no real blood or clotting mechanism. (Hints on page 12)
Publication of this proposal could be useful to terrorists because it gives a clear indication of what the US Government is expecting ... and what they are not expecting!
SysBio13 Asgn_9D_Class_07_DTRA RFP__2013_09_17
ReplyDelete0. Knew: general structure based on the last two papers and basics of what a HoC needs to encompass
1. Learned: DTRA's use for HoC. Really concerned with open system and on-line analytic capability.
2. Questions: How/why did they choose these 4 organs? In section on Human Organ Constructs, why is the use of decellularization methodologies ranked as high priority? (What is this technique really used for?)
3. Presentation: different options of cells for the OoC - already commercial ones vs. newly engineered
4. Thoughts: If the data for production of biomarkers associated with deadly agents in humans is not available (which makes sense) and so data from animal testing is used to judge the platform, don't we run the risk of building an animal on a chip (not human specifically)?
0. Knew: General government interest in OoC
ReplyDelete1. Learned: A sort of composite resume from the applying team is required for approval, they want the technology to be distributable, proofed by a third party gathering the same results. DTRA’s touted rationale for promoting OoC gains is for defense against a potential chemical attack on US denizens
2. Pressing: For proof-of-concept they want an MCM response to a known agent comparable to that of a human and they define the most important parameters to evaluate fitness, but what differences are they looking for in the ADME process compared to pure research.
3. Presentation: what are/viability of, engineered cells
4. Thoughts: They understand it has to be a cooperative effort and it’s good that they offer a platform for team-building.
0 Knew: I didn't know anything about government interest in OoCs.
ReplyDelete1 Learned: The defense applications of OoCs - what a call for proposal would look like, what all must be concluded, lots of preparation!
2 Pressing: What is meant by "open system" (p. 4). Also what exactly is the "decellularization approach" described on p. 5? Is it used just to get a scaffold? How is it achieved? Also, why don't they want the offerors to use serum in the blood surrogate?
3 Presentation: Funding for OoC research
4 Thoughts: This was a good read to know what is expected when one is applying for funding and what organizations are interested in funding research.
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ReplyDelete0. Knew: OoCs were being developed for defense applications.
ReplyDelete1. Learned: Effectiveness of OoCs must be tested using biological agents such as Marburg virus, Sarin, and anthrax. Yikes! Fitness of the OoC will be evaluated by dO2, temperature, pressure, pH, osmolality, metabolic by-products, viability, and functionality.
2. Pressing: Who is doing the Marburg and Ebola testing? This just got real. How were the specific response criteria established? How much of the platform development is confidential / secret?
3. Presentation: Viruses on chips
4. Thoughts: it was interesting to read the rules of the game.
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