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.
Wednesday, September 4, 2013
SysBio13 Asgn_5C_Class_05_Article_10_2013_09_05
Read Article 10:
Knut. Schmidt-Nielsen. Organ size and tissue metabolism. In: Scaling:
Why is animal size so important?,Anonymous New York:Cambridge
University Press, 1984, p. 90-98.. The primary goal is for you to be
able to explain the challenges in building multiple, compatible organs
on a chip. You now have the advantage of having read two papers on OoC
scaling.
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0. The basics of scaling and a general concept of why scaling is important.
ReplyDelete1. I learned about oxygen consumption / metabolism and that mitochondrial densities in muscle is inversely related to body mass.
2. The study highlights the correlation between mass and metabolism as measured by oxygen consumption but what are the variations in the oxygen consumption in things that are unhealthy. If we want an OoC in order to study a chemothearpeutic and we scale to health individuals we potentially miss the real effects in a sick person since their metabolism could be altered.
3. It would be interesting to see the tables plotted with fit lines and their slopes.
4. Scaling as based on this 1984, like today, is important in order to understand the difference between in vitro studies and in vivo effects. A mouse is not a human.
David Wooten
ReplyDeleteSysBio13 Asgn_5C_Class_05_Article_10_2013_09_05
0. Knew: Different organs scale differently
1. Learned: Metabolic rate in vitro declines more slowly than in vivo, but there is evidence that tissue slices give "some approximation" to in vivo rates.
2. Pressing ?: How important are mitochondrial density in determining metabolism?
3. Presentation: How OoC mitochondrial densities compare to in vivo.
4. Thoughts: This paper summarizes some key scaling questions, but it would be neat to read an "updated" version of the same paper.
I like that presentation question. I think working out increases skeletal muscle mitochondrial density. Perhaps the same is true for a hard working liver or brain? If there is a difference, it would certainly bolster the idea of moving away from cell cultures towards realistic OoCs
DeleteFrank "Edad" Block, Jr.
ReplyDeleteSysBio13 Asgn_5C_Class_05_Article_10_2013_09_05
0. Knew: General ideas of scaling.
1. Learned: Mitochondrial density ... total mitochondrial count in a liver from a large animal vs. a small animal.
2. Pressing: Can't determine BMR in a cell culture! You have to do it in the whole animal! (page 93 middle). How, then, do we have ANY idea what the O2 consumption of a specific organ on a chip is, vs. what it should be, vs. what size it is and should be, etc.?
3. Presentation: Factors that CHANGE the metabolic rate of an organ, or of an organ on a chip
4. Thoughts: Our organ on a chip is resting. Is it sleeping? Is it supposed to be sleeping? What happens if the organ on a chip walks around or runs at maximum speed?MANY things in the organ on a chip would have to change to compensate for this, just as in a human being!
0. Animals of all sizes have similarly sized cells.
ReplyDelete1. Smaller animals have muscle cells with greater mitochondrial density.
2. How was metabolic activity of each organ determined? If our only data is from tissue slices (Table 8.3) then we may be chaining metabolic activity of the organ significantly. Could measurements be made from individual organs in living organisms?
3. Measuring O2 consumption of whole organs without resorting to tissue slices.
4. Thoughts: It seems that much of the scaling data we have is based on tissues that have been significantly modified from their state within the body. This could greatly alter their metabolism.
Abigail Searfoss
ReplyDeleteSysBio13 Asgn_5C_Class_05_Article_10_2013_09_05
0. Knew:Metabolic rates of organisms decrease with increase in size. Cells do not vary much in size between large and small animals.
1. Learned:The difficulties of studying metabolic activity of individual organs (especially since the composition matters). The mitochondria density is not constant for different mass.
2. Pressing Question: The article says that the summated tissue respiration is sufficiently close to the actual total body's respiration (on page 95). Is this a big stretch? Can any of these tables be taken to be accurate since the organs are not in the actual organism when measured?
3. Presentation: Current ways to measure metabolic activity in organs. Any that are performed while the organ is still inside the organism?
4. Thoughts: Gives a good overview of the ways people have already thought to try to compare metabolic rates of organs to overall organism metabolic rate. (Keeps us from thinking they/we should try one of these options...they already did!)
0. Knew: Different organs and tissues scale with different with different coefficients.
ReplyDelete1. Hemoglobin and cytochrome c concentration is proportional to body mass.
2. What is the true basal rate for an organ? How can we control it? What effect will controlling it have on the output of the organ?
3. Scaling tissue metabolism
4. The problem is summed up at the bottom of p. 93 "Evidently, the search for a standard method for determining tissue metabolism is not easy."
Jie Zhao
ReplyDeleteSysBio13 Asgn_5C_Class_05_Article_10_2013_09_05
0. Different organ have different BMR.
1. Metabolism is closely related to mitochondrial densities.
2. If we take into consideration just the different physical properties of different organ, it might explain some of the BMR difference, ie. The surface area/tissue mass and so on
3. Organized Figure representation of oxygen consumption, mitochondrial densities, BMRs and so on for different organs.
Cameron Stewart
ReplyDelete0. Knew: Mitochondria density of the liver should be inversely proportional to body mass. That’s why caffeine can kill mice, their cells are already performing near their peak ability.
1. Learned: Summing up the metabolism of the individual tissues in vitro can give a rough estimate of the metabolism of the organism in vivo. I’m surprised at how close it was and I wonder, given modern tools, how much better those measurements could be made. Also, I was surprised by how much energy brains use.
2. Question: Given that metabolic rate is an important factor in the body’s metabolism of drugs, are drugs ever made with the intention that the patient should be asleep or active while taking it? Should patients being given drugs which preliminarily passed mouse testing be told to exercise while metabolizing the drug to make their bodies more mouse-like? Also, how different is allometric scaling from functional scaling? Are they identical down to the size of the smallest mammals?
3. Presentation: About the relative allometric scaling of important organs.
4. Very relevant to OoCs and HoCs.
0 Knew: BMR scales down as body size increases.
ReplyDelete1 Learned: The decrease in relative BMR of larger animals might have to do with the decrease in density of metabolic machinery in cells. It is not directly correlated with the change in size of the metabolically important organs.
2 Pressing: How do we apply this to OoCs? What implications does the change in BMR have? We want to recreate normal human BMR in the cells in the OoC? or a scaled down BMR? -- since it can't be dependent on number of cells, do we need to alter the metabolic machinery of the cells? How does BMR not scale automatically?
3 Presentation: Implications of BMR in the scaling of organs
4 Thoughts: This helped me to understand why BMR is so important when it comes to scaling.
Rui Wang
ReplyDeleteSysBio13 Asgn_5A_Class_05_Article_10_2013_09_05
0. Knew: Oxygen consumption of different tissues does change with body size.
1. Learned: The metabolic equipment of tissues corresponds to the needs of the total organism.
2. Pressing: How to apply the mitochondria density to quantify the metabolism?
3. Presentation: the importance of mitochondria
4. Thoughts: The density of mitochondria and oxygen helps me better understand various tissue metabolism. What other factors can be taken into consideration to explain part of the tissue metabolism?
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ReplyDeleteJPW