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. KNEW:
ReplyDeleteLike in the other TEDx video by Geraldine Hamilton, I was aware of the disparity in drug interactions in cell cultures, animal testing, and the human body. The manner in which cells interact with their environment is dramatically different in lab environments versus in in vivo environments and this in turn does not permit proper drug testing. This causes unforeseen effects to emerge in clinical trials that should have been detected beforehand.
I was also aware of the interdisciplinary nature of organ-on-a-chip studies and the need for separate disciplines to work together more often.
1. LEARNED:
There is a problem in the lab environment where we cannot predict the effects on drugs on the human body with cell cultures and animal testing because we're not aware of the potential organ-organ interactions that result because of the drugs and we only have a black box understanding of many of these drugs.
The hope of the organ-on-a-chip technologies, Athena, is that we can fully simulate the human environment in vitro by connecting the isolated microfluidic chips in tandem that would promote the endemic cross-talk and let us predict the drug-body interactions.
2. PRESSING ?
Are we aware of the relative size of each organ chip needed to make Athena properly represent the human body?
Are there organs or body components that cannot be truly represented by organ chips technologies? This is rather general, but are there reactions or processes that are not dependent on relative concentrations, but on absolute quantities or environments that cannot be simulated in Athena?
4. THOUGHTS:
The phase-space and silo concepts were an interesting way to present the need for interdiscplinary work. The desire for higher dimension phase space leads to me wondering how much computational power would be required to simulate all the gene expression requirements on a organ, system, and time basis, along with changes in these requirements due to perturbations in the system as a result of drugs. I really liked the more casual tone of the presentation!
2) Yes - an earlier class wrote a scaling article. Missing organ problem...
Delete4) The numbers problem is gigantic!
0. Knew:
ReplyDeleteAs for assignment 7A, I am familiar with some of the physiology involved and of the existence of the chip initiative. From what we've discussed in class, I also recognized the breadth of expertise needed to develop these chips.
1. Learned:
The overall goal is to create Athena that will incorporate multiple organs into 1 piece of hardware. Is Vanderbilt behind any of the compilation of the organs on chips being developed by the rest of the team?
2. Pressing ?:
This presentation initially made it sound like cells make up the actual chip, but this would be more like research trying to physically grow organ systems in vitro. It's actually a silicone or plastic chip and cells are sent through it, right? That was my understanding before.
Could some of the seemingly less important organs listed be interacting with the output of the organ system-on-a-chip? Will it ever be beneficial to model these?
3. Presentation:
What will Athena (or any compilation of the chips) really look like?
4. Thoughts:
Great talk that brought all of the readings and the previous talk around to how we've been discussing/interpreting in class. Really liked the explanation of "gene phase space".
1) I am no longer part of the ATHENA team, but am working with another group. I will describe in my SD talk.
Delete2) Silicone or plastic chip.
3) Will show
4) Good - we need to have Phase Space in our working vocabulary.
Ben Terrones
ReplyDeleteSysBio16 Asgn_7B_Class_07_TEDx_02_2016_09_15
0. KNEW:
How drugs are tested in dishes, animals, and eventually humans. Expression of genes is different in every organ, which makes things complex.
1. LEARNED:
One of the most important things I learned is why we need homunculi, which is because biology is very complex, and we want to be able to know how organs interact with one another. It is important for drug testing to be able to use human cells and have organs interact with one another, which is what the homunculi will do.
2. PRESSING ?:
Is Athena what the “machine” was supposed to be from the other talk? How do you know which organs to include and which are not necessary in Athena?
3. PRESENTATION:
More on Athena, comparison of Einstein and Doc Brown
4. THOUGHTS:
The intellectual phase space diagram was awesome. I really enjoyed this talk and it helped me understand the purpose of building organs on a chip and what/who it takes to get to that point.
No connection between ATHENA and Harvard. I used to be part of both.
Delete3) My life got easier when I realized that Doc Brown was my role model.
0. Knew:
ReplyDeleteI knew the information about organs on a chip from the previous video. I knew what multi-dimensional phase spaces are. I knew about swings.
1. Learned:
I learned about how creative you can be with swinging! I learned about the importance of multi-dimensional phase space (in biological systems, intellect, behavior, etc.). I also learned about the steps of usual drug testing (dish, then mice, then humans) and that homunculi need to be inserted before the human testing. I learned about ATHENA and that the goal is to connect many organs on a chip to view how different organs communicate and react to each other. I learned about how to visualize the importance of interdisciplinary research.
2. Pressing Questions:
What is the current status of ATHENA? Are there any organs that have not/cannot be implemented on a chip?
3. Presentation Topic:
A presentation on ATHENA discussing where the project is now and more specifics would be interesting to see a presentation on.
4. Thoughts:
This video helped me understand the importance of non-silo mentality to solve pressing problems. It was great to see another perspective on the organs on a chip project.
1) Good.
Delete2-3) ATHENA died but is being resuscitated. I am no longer part of the ATHENA project.
4) Good
0. KNEW:
ReplyDeleteI knew about organs on a chip from papers that have been discussed in class as well as the other TED video that was assigned. I knew the basics behind phase space and its multidimensional nature. I enjoyed the swing example for clarity.
1. LEARNED:
I learned that a homunculi is a small humanoid creature, or in this case a human on a chip. A homunculi is necessary in determining how drugs interact between the various organs. I also learned that phase space is relevant in the context of interconnected organs on a chip because of the complexity that arises when you associate several interactions in series.
2. PRESSING QUESTIONS:
The biological phase space is overwhelmingly complex, so is the goal of Athena and organs on a chip to understand this phase space or to make a product that is useful for testing drugs?
3. PRESENTATION TOPIC:
Drugs that have failed in human trials because of interactions between "silos" that were not seen in petri dishes.
4. THOUGHTS:
I was able to learn more about the problem that organs on a chip are trying to solve. This video also helped me understand the complexity of this problem by using phase spaces.
0-1) Good
Delete2) Yes, both. I think that understanding may trump pharma.
3) Yes!
4) Good.
Kelly McGee
ReplyDeleteHomunculi and I
0: I knew about the basics of organs on chips, the importance of addressing how organs "talk" to each other, the importance of diversity of thought in design teams, and how much of a boss Leonardo Da Vinci was.
1: I learned the definition of phase space and that 40% of human drug failures relate to cardiac issues.
2: If we do manage to create extremely good human homunculi, what will be the virtue of mice trials at all?
3: The blood-brain barrier.
4: I can see it now...
"Swings are hard." -Joseph Coombe
2) Does an organ on a chip directly mimic in vivo conditions? Or do they just allow us to better understand how some of these cell types interact and the effect that a drug will have on many cell types and their interactions? Is it feasible to include every tissue type (and subtype) from every organ in the body?
DeleteIf we did include every tissue... would we create an actual person?
DeleteYeah I wonder if the benefits of using human cells will outweigh the benefits of using a whole organism. I imagine we will probably keep using them in tandem until the mice find out
DeleteMice will be important for the things left out of a homunculis.
DeleteStephanie - both. Not all organs.
Mike - exactly.
SysBio16 Asgn_7B_Class_07_TEDx_01_2016_09_15
ReplyDeleteThe Homunculi and I – Lessons from Building Organs on Chips
0. KNEW
Importance of collaboration in science! Also the basics of OoC.
1. LEARNED
I learned what homunculi are and about ATHENA. Also learned who George Westinghouse was.
2. PRESSING
What is the status of ATHENA? How does its user interface work? How does ATHENA relate to the instrument mentioned in Hamilton's talk? Will there be pediatric/geriatric versions of ATHENA? How would they differ?
3. PRESENTATION
Current state of ATHENA from an engineering perspective
4. THOUGHTS
I really enjoyed the physics/engineering/physiology intellectual phase space part of the talk. It made me start to think about what fields I might include in my 'phase space' as my career develops. Its BME/finance now but could expand to something completely unexpected in the future.
It was also interesting to see the contrast between these two talks. Since scientific papers tend to adopt a very professional tone, I don't tend to think about the personalities that drive the work–even though play a major role determining how scientific questions are approached. I'm excited to learn more about OoC and developments in linking them together. Very interested in learning how various OoC interface with one another, and approaches to UI/UX in linking OoC.
I completely thought of the phase space as it relates to my career as well! I am also BME but do computer science work. I big question I have is, is it "better" do have more dimensions or have more expertise in our area like Einstein? I wonder if you could somehow "answer" that question with a mathematical model utilizing the phase space. Seems cool! As an aside, I have considered pursuing opportunities to learn finance as a BME. Would love to hear about your experiences.
Delete4) Nothing could make me happier than for my talk to help you sort out your life/career phase space.
DeleteThe two talks and the two speakers are quite different.
Chinowsky_TheorSysBio_PCRC_09122016
ReplyDelete0. Knew
As with the previous TEDx talk, I am aware of the global health crisis of drug discovery—in vivo cultures are too isolated and artificial, and animal models, while useful research subjects, cannot accurately represent human biology.
1. Learned
“Big” problems (or maybe big opportunities for improvement is a better/more positive way to think about it) require collaborate and interdisciplinary thinking—I loved the idea of intellectual and behavioral phase space, and I think it’s very important to train interdisciplinary scientists that are capable with collaborate across many fields.
2. Pressing
How would one account for cell signaling between organs? I’m assuming that multiple OoC devices would be connected, or would they be merged into one massive HoC(human on a chip)?
3. Presentation
The steps/thought process of engineering something like ATHENA. As primarily a physicist by training, I feel like I can grasp the theory, but how does one bring it into practice?
4. Thoughts
That was probably the best description of phase space that I’ve ever seen. I’m going to integrate use of the term “silo thinking” into my vernacular for sure. I think that informal “simple” speech is an essential part of making science accessible to the general public and allowing for more collaboration between fields. I think this talk beautifully illustrated how one can still convey the ideas of science without getting caught in the jargon of the field.
2) Is it normal to have kidney and liver and heart cells all touching one another? If they were, could we possibly mimic all of their in vivo environments on a single chip? What limitations could this cause? Would this affect how the cells signal with one another (how do they signal in the body)?
DeleteNot touching, but sharing humoral factors. The hard ones may be the neural connections (vagus, etc.)
DeleteGlad you like the phase space presentation.
Natalie Hawken
ReplyDeleteAsgn 7B: TEDx 02: The Homunculi and I: Lessons from Building Organs on Chips
0. KNEW
I knew the basics of organs on chips from our earlier discussions in class, including how we want to connect these chips. I knew how this project required many scientists with many different specialties. I knew how trials with mouse models don't always match the results in humans.
1. LEARNED
I knew the basics of phase space, but I didn't realize how complex the phase space could become with all of the dimensions that need to be included. I learned how we can mimic the brain for drug trials by just having the vessels, the blood-brain barrier, and the CSF. I learned how we have a very realistic plan for creating a microhuman, Athena.
2. MOST PRESSING QUESTIONS
Has Athena been made and tested yet? How far along are we in this project?
What systems are used to monitor the chips to make sure they are working properly?
How commercially viable are these chips? Will they be able to be mass-produced for pharma?
3. PRESENTATION TOPIC
How do each of the organ chips in Athena mimic the organ (what inputs and outputs are included, what fluids flow in each, what cells are used)? Pretty much do a breakdown of each of the organs involved.
4. THOUGHTS
I had always been interested in trans-disciplinary research topics and would love to work in a lab that has more integration with other departments. I really enjoyed the part of the talk discussing engineering vs physics vs biology vs physiology phase space.
1) Biophase space is ginormous.
Delete2) Organs on chips are reaching out into the market. Check out *TissUse*
4) :)
PCRC
ReplyDeleteSylvia Morrow
Asgn7B_John Wikswo -- The Homunculi and I- Lessons from Building Organs on Chips
0. KNEW: I realized within the first 10 seconds that I had already watched this about a year ago; however, I still found the video engaging and informative. Also I'm convinced that the semi-arbitrary division of academia by discipline is in need of revision.
1. LEARNED: Despite having learned about phase space previously, for whatever reason it's one of those concepts that doesn't stick well in my memory, so I always like to have it re-explained in new ways. I guess it's basically a multidimensional coordinate space where each dimension represents a physical variable so that when you pick a coordinate in phase space, that coordinate represents a state of the system. Assuming infinite and continuous axes, this leads to infinite possibilities for the state of the system?
2. PRESSING ?:
--How well-recognized are the negative repercussions of silo mentality in academia?
3. PRESENTATION:
--N/A
4. THOUGHTS: This was pretty different from Geraldine Hamilton's presentation. It spent time on a number of complex topics such as phase space and silo mentality that Geraldine chose to leave out. For me the net effect was less of a focus on how/why we want the integrated organ-on-a-chip system to a broader philosophical point on not restricting yourself to some predefined notion of your 'field of research'.
2) Well recognized, but that does not mean that they are being addressed at the department level.
Delete4) As you may have noticed, I try to address broader philosophical issues.
To respond to everyone Re: how do we make OOC and Athena updates, Dr. Wikswo would like to give his talk from SD about organs on a chip at some point, we hopefully will get to address some of this in the future.
ReplyDeleteSP & I will figure out when to insert SD.
Delete0.Knew: I knew from Hamilton’s TEDx talk why chip organs are useful, what their general structure is, and how they can help with anticipating drug effects; I am now able to apply the term “homunculi” to these miniature versions of humans. I also knew that building these chip organs required knowledge of people of different disciplines to facilitate creative ways of solving problems.
ReplyDelete1.Learned: I learned about genetic, behavioral, intellectual and multidimensional phase space (I think the swing representation of multidimensional phase space was particularly helpful). Also, the first time I heard of silo mentality was in this TEDx talk. I believe the most notable thing I learned about was the ATHENA chip. Learning about ATHENA gave me a great idea of how advanced chip organs have become towards mimicking actual human beings.
2.Pressing Questions: It was mentioned in the talk that the brain chip organ would not count, but that it would tell us whether drugs were passing through the blood-brain barrier. I know that the primary goal of these chip organs is to be able to better predict the effects of drugs, but is it possible that the chip organs developing more advanced capabilities would be possible or useful (maybe not as far as the brain chip organ being able to distinguish certain numbers or count)?
3.Presentation: I would like to learn more about genetic phase space; a brief presentation of this would be helpful. If there is time, I would be willing to look into this and give the presentation.
4.Thoughts: This TEDx talk and the one from Hamilton were great overviews about homunculi and their usefulness. They encourage me, as a biomedical engineering student and as an interested person in general, to get more involved in chip organ research in the near future.
I have not researched it but I think researchers have gotten mathematical computation out of neurons! I agree it would be awesome to bring advanced capabilities to brains on chips and I think it can be achieved! I wonder if we could ever create a "better" brain than we could model with a computer. You could argue that our brains are better and so what if we created a brain as good as ours?... Would we be creating a conscious thing? Woah
DeleteWe will do more on genetic phase space!
DeleteMike - *thinking brain on a chip* update?
0. KNEW
ReplyDeleteBefore watching this TEDx Talk, I was familiar with the aspects of organs on a chip discussed in class thus far (chemical networks, data mapping, etc), as well as information presented in the first TEDx Talk. This includes the logistics and cost of modeling organs on chips, the ability to eliminate animal testing in many cases, the diversity of test subject models (taking into account all demographics), and the possibility of interconnecting organs to model human organ systems.
1. LEARNED
First, I was informed of the meaning of homunculi and the necessity for using this scaling idea in order to predict the effect of drugs on human physiology. Then, the talk gets into phase space dimensionality and the idea of having a data point for every time and dimension, which comes into play in coordinating people from varying professions in order to build homunculi.
The bulk of information presented is the interaction between organs and the inadequacy of in vitro and animal testing in determining whether a drug will work in a human with no serious side effects. The talk presents a startling fact that 40% of drugs fail because of cardiovascular complications.
I think the lesson of the talk is to not limit oneself or others to one particular “silo.”
2. PRESSING ?
What goes into determining material characteristics of the chip on which the cells are planted? What factors into engineering design of the organ? (What exactly is electronic control of the organ?)
3. PRESENTATION
phase space in depth (is this related to the pathway network modeling we have been talking about?)
4. THOUGHTS
I enjoyed this talk thoroughly…a lot of breadth with a good amount of depth. It’s a nice change from the papers for now.
1) Yes - avoid silos or drill through or climb over...
Delete2) Good questions, but beyond this class.
3) We will do more with genetic phase space.
4) Good.
0 Knew: About microhumans and the reasons for their existence as well as the explanations of phase space.
ReplyDelete1 Learned: Refresher on silos and the detriment to creativity that they represent
2 Pressing Questions: How is the communication between organ on a chip devices detected?
3 Presentation: Microfluidic systems
4 Thoughts: Fun to watch and educational
2) ELISA and UPLC-IM-MS
DeleteJohn Wikswo -- The Homunculi and I- Lessons from Building Organs on Chips
ReplyDelete0. KNEW:
I actually watched this video around a week before class started. But before I watched it, I didn't know anything about biology or drug development--in particular, I wasn't aware of the different stages drugs had to pass through to make it to market. Without thinking, I think I had always imagined that there was some other intermediate step between animal testing and human testing. "Don't we have the technology for that?"
1. LEARNED:
I learned about the current drug development paradigm (body tissue in silos, then animal testing, then human trials), and efforts by Professor Wikswo and others to improve it. It is surely a good thing to be a little bit more careful about drug development--after all, people have previously lost their lives to ill-considered drugs that prematurely went to market, or to human trials.
I also used the video as an opportunity to think more about my own motivations regarding and interest in science. Surely the way that many scientists approach problems (as is pointed out in the talk) is similarly compartmentalized; rather than there being strict divisions between the realms of physics, chemistry, biology, and so on, each discipline is really just a different piece of the same thing. It is worth being interdisciplinary in approaching difficult problems like this, because no one perspective has all the answers.
2. PRESSING ?:
My most pressing question is rhetorical. In recent years there has been lots of fuss made about making scientific work increasingly interdisciplinary. So...will that stick? Will it become more commonplace for individual scientists to try to speak different scientific languages, or is this just a fad? Or worse, something people talk about but only make a passing effort to actually do?
I also wonder (naturally) how effective the organ on a chip paradigm will prove to be. That will probably ultimately depend on the complexity of the chip, which is a choice that must be made. That is, the chip must be complex enough to represent complicated processes that happen in the human body, but simple enough to hopefully be inexpensive and widespread.
3. PRESENTATION:
I would like to see a presentation on genuinely interdisciplinary work, where researchers from a few different fields have to combine state of the art ideas from each field to arrive at a satisfactory answer to some question. I am not sure if this really happens--typically work on the interface of several fields is much more 'in one field' than another, and it seems to me that it is much more likely that work is superficially interdisciplinary (incorporating ideas that are not really that interesting in their original field) than not.
4. THOUGHTS:
I am still making an adjustment, but I think I see the overall picture more clearly now. I am also beginning to realize that I might have some tools that other people don't have that may be helpful.
2) It will stick. Low-hanging monodiscipline fruit has been largely picked.
Delete3) Hard to do.
4) GOOD!
Stephen Lee
ReplyDeleteClass 07, Assignment 7b
TEDx 02 John Wikswo -- The Homunculi and I- Lessons from Building Organs on Chips
(0) Knew:
Knew a good deal from working with students in VIIBRE about microfabrication and organs on chips. Knew about the necessity of inter-organ communication in testing drugs in human models and the novelty of homunculi for addressing this problem.
(1) Learned:
The idea of phase space was more clearly defined for me. I also learned about ATHENA and the consortium of universities working to develop a “millihuman”, and finer details concerning organ chip facilitation and development.
(2) Pressing Questions:
My questions concerning organs on chips all center on the validity of human organ reproduction for pharmacological assays. Human organs are incredibly complex and in some cases rely on dozens of cell types and crosstalk between them. In this regard, what level of detail is sufficient to gain worthwhile insight into how a living, breathing patient will respond to a drug? Has the concept of a homunculus ever been borne out in an early phase trial?
(3) Presentation Topic:
A presentation regarding human organ reproducibility and microfluidic accuracy in representing different physiological environments. Whether certain polymers/materials would be more appropriate for certain organs, whether there should be a diversity of flow between organs, incorporating many cell types, etc.
(4) Thoughts:
Dr. Wikswo’s talk at TEDx was clear and digestible, even for someone with limited knowledge of his work. Organs on chips was one of my principal interests entering SyBBURE, and I’ve worked periodically with them while at Vanderbilt. I’m excited to hear how this effort has developed and its trajectory moving forward.
2) Homunculi are just now coming on line.
Delete3) We will get to the gene-expression analysis
4)Good
0. KNEW:
ReplyDeleteI knew about mathematical spaces. I knew about basic human anatomy. I just recently learned the process of testing drugs in petri dishes and such. I knew about microfluidics. I knew about the concept of connecting organ chips together.
1. LEARNED:
I learned what phase spaces are. I learned about why specifically organs on chips are beneficial for pharmaceuticals. I learned about the importance of the blood brain barrier for the brain on a chip. I learned more in detail from the schematics about linking organ chips. I found out about the importance of collaboration in the pursuit of Athena. I learned the concept of the intellectual and behavioral phase space and how these relate to the needs for a human built with organ chips.
2. PRESSING ?:
Has any of these chips been attached yet?
Do we know how most organs talk to each other?
3. PRESENTATION:
A presentation should include the organs on a chip but maybe specialize on the end goal, or how the signals between them might be measured.
4. THOUGHTS:
The end of this TEDx talk was very inspirational! I enjoyed the plug about ADHD and how this can relate to the greater context of collaborative and communication.