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:
ReplyDeleteI 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.
1. LEARNED:
I learned about the diminishing returns of R&D investment on drug development.
I learned that we've already managed to artificially simulate an immune response to bacterial infection in the lung, which is visually stunning and an awesome achievement.
2. PRESSING ?
Is the higher ratio between R&D cost to drug development a direct result of a lack of proper drug testing or are there other factors, such as difficulty in synthesizing effective drugs, responsible?
Do we commonly use cell lines derived from children? Geraldine Hamilton made it seem like we never conduct tests on children, which I believe is not necessarily true.
3. PRESENTATION:
Covering currently developed and existing organ-on-a-chips would be nice, because I'm not entirely sure what exists at the moment and from what groups.
4. THOUGHTS:
I thought about Geraldine Hamilton's comment on making a personalized chip that would perfectly mimic a drug's reaction in your body and how extracting the cells required to create that chip could be both invasive and painful. I wonder about how long the lifespan of that chip would be, the cost of upkeep, and all the ethical and legal issues that could result from obtaining cells from people on a large-scale basis.
I haven't thought about any ethical issues associated with this. I'm also curious if this has come up at all
Delete2) I think a lot of it comes down to we don't know as much as we think we do about biology and biological processes. We don't know enough on the molecular level to accurately predict what will and will not have an effect on something. Proteins weren't made to come into contact with foreign compounds; they weren't designed that way. The cost just to screen for a hit in millions is huge, and then we have to figure out how to actually deliver that where we want it. Many of the first drugs were things that had natural sources (ocean, forest, etc) and had been used for thousands of years.
Delete3) Dr. Wikswo will give his organ on a chip talk from SD at some point.
4) Have you read "The Immortal Life of Henrietta Lacks"? It addresses many ethical concerns that come up with collection of human tissue. Definitely recommend to everyone wanting to go to into something related to medicine or research.
0-1) Good
Delete2) The basic problem is the inability to predict drug efficacy and safety from 2D biology on plastic with animal or immortal cells, complicated by the complexity of biology and the multitude of possible off-target effects. It is NOT a one-disease, one-gene, one-drug world!
3) We may get to look at more OoCs, but I think we need to focus on MoA.
4) Cells could be created and frozen down. Might cost $50k today to make a custom NVU/BBB. Organ last ~1 month.
Definitely read "Immortal life.."
For a shorter, audio version of the Henrietta Lacks story, this link is to an interesting podcast about her story.
Deletehttp://www.radiolab.org/story/91716-henriettas-tumor/
Sylvia Morrow
ReplyDeleteAsgn7A_Geraldine Hamilton -- Your body in a microchip
0. KNEW: That the organ-on-a-chip program existed, and that the goal was to connect these systems.
1. LEARNED: Some nice simplified foundational information such as the standard method of testing drugs (dishes -> animal -> clinical trials). The most valuable thing I learned was the 'home-away-from-home' idea of why organ-on-a-chip is so superior to cells in a dish and a basic understanding of the actual chip structure that creates that environment.
2. PRESSING ?:
--Still not 100% clear on where the cells that are put on an organ-on-a-chip come from. Do they all come directly from humans? Or are some grown in the lab? And if they're grown in the lab how is that any different than doing the test in a dish?
3. PRESENTATION:
--Don't know if this is beyond the scope of this class, but I would love to hear more about the organ-on-a-chip from an engineering perspective.
4. THOUGHTS: She presented a linear and story that made it very easy to understand/follow her line of thought. The flipside of this is that she presented the polished version of the story without offering a sense of the challenges that were faced or the challenges still being faced.
2. Good question- I'm assuming the end goal would be to extract human cells to test in the chips to overcome issues associated with translation, but maybe animal cell lines are used in development?
DeleteI think the main difference from a culture dish is providing the surrounding cues that affect cellular activity. From what I understand, the goal of the chip is to simulate any mechanical or biochemical cues in vitro that will effect cell function.
3. I would like to hear more from an engineering perspective as well
2. I'm not sure about the cell sources, but the advantage of lab-grown cells in organs-on-chips (OOC) over lab-grown cells in a petri dish, is (like Madison said) that the OOC cells may have more physiologically relevant structure/function relationships. By more precisely controlling cell population, composition and architecture, and other environmental forces (e.g. shear stress, laminar fluid flow), you can more accurately control cellular differentiation/activity.
DeleteThis is important because cell differentiation is also a determinant of how cells behave. If you start with a terminally differentiated cell population of interest in a petri dish, it is possible for them to dedifferentiate into an early cell type, so OOCs are a way to prevent that. OOCs also make it possible to engineer 3D cell constructs (like ducts).
2) There are various types of cell lines. Many of the ones that are used in research currently are cancerous, or have been transformed with a virus to grow without stopping. This makes it easier to culture them, as you have a basically unlimited supply of cells. These have been cultured many time. The first cell line, HeLa, has been growing since the 50's!
DeleteFor OOC, primary and secondary cell lines are ideal, as they are cells taken from a tissue and dissociated into single cells and grown. You can go to Google for more information about this.
If you want to learn more about protocols and characteristics of cell lines, just to see what it's about, I recommend going to ATCC.
3) I think Dr. Wikswo is going to get to this at some point.
Good discussion!!!!
DeleteWe may need a talk on **Sources of Human Cells** They include cadaver, fetal, organ donors, etc. iPSC-derived cells will be the best because they will be patient specific.
0 Knew: The reasons for using organs on a chip as well as connecting them and that efforts were underway to do just that
ReplyDelete1: Learned: Gained some data on the cost of the pharma industry
2 Pressing Questions: Where is she know with her research for connecting organs?
3 Presentation: Microfluidic Flow
4 Thoughts: She presented a very clear notion that the world needs her product.
She gives a good product pitch!
Delete0. Knew:
ReplyDeleteKnowing some of the physiology behind the organ systems discussed (the lungs mostly) helped me to understand the benefits of modeling the organs on a chip. Similarly, having some experience with basic cell culture, I definitely can see how these organs on a chip will improve the knowledge gained and potential advancements these will produce.
As the others have stated, I knew that creating these chip-based systems were of huge interest and have learned about the initiative discussed through class discussion.
1. Learned:
I really enjoyed the video showing how the chambers in the chip worked. I didn't realize that vacuum chambers and fluidics are combined for these devices.
2. Pressing ?:
Have any of the organs on a chip been combined yet?? I'm interested to see how this will be implemented and what the first investigations might look like.
3. Presentation:
I agree with Amy that covering the existing organ on a chip models/progress on these would be insightful
4. Thoughts:
I thought the talk was very easy to follow since we've been discussing the idea in class. Interesting quote/paraphrase- 'the more money we spend on R&D, less drugs make it to the market'... it's definitely a problem facing many biomedical companies
Several groups have demonstrated between four and 7 organs talking to each other.
DeleteBen Terrones
ReplyDeleteSysBio16 Asgn_7A_Class_07_TEDx_01_2016_09_15
0. KNEW:
I knew that it costs a lot of money to get new drugs on the market and they fail all the time because we can’t accurately predict how they will affect humans. I knew sort of the idea behind organs on a chip but not how they work.
1. LEARNED:
This video really explained exactly what an organ on a chip is composed of and how it works, especially the lung on a chip. Dr. Hamilton also explained the possible applications of the lung on a chip such as studying immune response, finding new treatments for diseases, testing safety of chemicals, changing clinical trials to make them more specific, and personalized medicine. The most exciting part to me was the possibility of connecting chips and creating a “virtual human on a chip.”
2. PRESSING ?:
I was a little confused about what exactly the “machine” would do? Is it like the human on a chip and then the researcher chooses which chip they want to study? Also she talked about mass-producing these chips, how expensive would the chips be? And then how expensive would it be for an average person to get personalized medicine by using an organ on a chip?
3. PRESENTATION:
The components of an organ on a chip, how its built.
4. THOUGHTS:
It was nice to take a break from papers and enjoy a good TEDx talk. This was a good video and I thought Dr. Hamilton did a great job making everything easy to understand and to see the potential in these devices.
2/3) Look up microfabrication techniques. This will give you an idea of how they are made and can let you look at costs a bit. Also look into cell culture. Cell culture can get expensive depending on what you're culturing, how much, and what you're trying to do!
Delete2) Yes. TOday, $10k's per organ...
Delete3) Maybe, but that really belongs to another class.
4) She gives a good pitch.
Kelly McGee
ReplyDeleteClass 07, Assignment 7a
Your body in a microchip
0: What I Knew: I was aware of the existence of organs-on-chips, the importance of dynamic forces and dynamic equilibria, and how microfludic devices are critical to organ on a chip applications.
1: What I Learned: # of drugs created per $ spent on creating drugs has consistently decreased over the past few decades. We can visualize immune system responses to infectious agents in real time.
2: Questions: "More often than not" animal trials fail to accurately predict human body responses. Really? What does that mean? Over 50% of drugs that have a positive effect in animal trials fail in human trials, or what?
How complete are the organs-on-chips in terms of ECF replication? ECF protein content, coagulation cascade, etc.?
What do the connective apparatus to/from organs on a chip look like?
3: Presentation Topic: Lymphocyte movement through epithelia, perhaps?
4: Comments: "We're not going to fully replicate the human body with these chips." Really? Not in the near future, but eventually? Why not? I think we could.
2. According to this (http://www.nature.com/news/2011/110928/pdf/477526a.pdf) 85% of therapies fail in clinical trials. This may be caused by a number of factors (efficacy, safety, financial/commercial viability, etc). Part of the high attrition rate is due to the fact that animal studies tend to focus on safety rather than efficacy. It's not that the drugs are necessarily shown to have positive effect in animal studies then reverse course in clinical trials. They may have been deemed safe in animal studies, but shown to be ineffective in humans.
DeleteThere are also some confounding factors outlined in the review. For instance, patients who participate in clinical trials are more likely to have sought other types of treatment first, unlike the animals which are being tested on. Clinical studies should be big enough that one person like this won't perturb the whole dataset, but it is something to consider. Prior treatments (etc. chemotherapy, radiation) could affect the pharmacokinetics in unanticipated ways.
2) At this point, many organ on a chip systems still use typical cell culture media, which would mimic the ECF and other nutrient delivery mechanisms. It provides what cells need to grow, and there are different media types and additives. You can visit ATCC to investigate different cell types and different things they need to just get an idea.
DeleteIn microfluidic chips, tubes are typically used to connect things and flow fluid in/out devices.
3) Outside class bandwidth, but very important. Systems biology of chemotaxis signalling would be closer.
DeleteKuniko - excellent point.
Stephanie - yes
0. Knew:
ReplyDeleteI knew about organs on a chip and why they are important in getting cell cultures into the correct dynamic environment for drug testing.
1. Learned:
I learned of the declining trend of money spent v. successful drugs made. I also learned about the specific properties an organ on a chip needs to account for (mechanical stress, biochemistry, function, etc.) to mimic the actual environment the cells would be found in as well as the specific parts of a lung on a chip.
I mainly learned about all of the possibilities that organs on a chip offer. I had originally only thought of drug testing, but I learned that testing reactions to harmful chemicals or diseases could also be a very useful application of organs on a chip.
2. Pressing Questions:
What type of cells/organs are easily implemented on a chip and which types are not? Is complexity the only obstacle for certain organs, or are there other factors that come into play?
3. Presentation Topic:
A presentation on where the organs on a chip research is today would be very useful, since this was presented in 2013.
4. Thoughts:
This video was a very understandable introduction to organs on a chip. I was able to grasp what organs on a chip are and why they are important. The whole idea is very fascinating to me.
I was thinking about the same question you have at one point. It appears epithelial cells would be great to put on a chip. What about specialized cells that require a specific spatial orientation in relation to others? I am thinking about the parts of the kidney and liver. To make actual organs on a chip, do we need to have collections of chips make up one organ?
Delete1) Good things to recognize.
Delete2) List is growing
3) We will have more later in the semester!
4) Good.
Mike - lots of people are working on epithelial. Both endo- and epi are polarized by flow or mechanical or chemical factors. Key to interfacial organs on chips -- a very big advance over 2D biology on plastic.
Chinowsky_TheorSysBio_PCRC_09142016
ReplyDelete0. Knew
Global health crisis of drug discovery—in vivo cultures are not representative of cell’s function and relationships within the body. Animal models cannot always predict human response to therapies because they are…not humans.
1. Learned
I feel like I know have a greater understanding of how OoC’s differ from organs themselves, while still accurately modeling an organ and its stress response to mechanical/biochemical factors. There is a “human on a chip” in development, and OoC’s may be able to contribute greatly to personalized medicine.
2. Pressing
Hormone and immune responses to drugs/infections. How do OoC’s account for types of responses that generally are regulated by the thyroid or similar glands? How is the imaging for OoC done? What are some limitations here?
3. Presentation
Something on “Design of an OoC”. Like a walkthrough of the architecture or OoC “blueprint”.
4. Thoughts
TEDx talks are such lovely ways to share novel ideas. This video in particular had lovely use of visual aids in addition to the speaker. Is there something holding up the introduction of OoC’s into clinical trials?
1) Much progress since this talk.
Delete2) We will get to this late in the semester - we did that in my class last spring.
3) Beyond this class
4) Validation!!!
1. KNEW:
ReplyDeleteI knew that the process of developing new drugs was long and costly, with the average drug costing over $1 billion before it is able to hit the market. I also knew that the cost of developing new drugs has increased substantially over the last 50 years.
2. LEARNED:
I learned that these chips simulate the mechanical environments that cells would experience in a human body (peristaltic motion for a "gut on a chip"). These mechanical chips help mimic the environment of the cells to produce more accurate in vitro results. Also, I did not know that these chips could be interconnected.
3. PRESSING QUESTIONS:
When did organs on chips begin to be developed? When is a skin on a chip going to be able to be used to replace animal testing?
If you could individualize chips using stem cells, how long would it take for a person to gather this information and test the potential drug?
3. PRESENTATION TOPIC:
How this technology has grown and where it is headed.
4. THOUGHTS:
This video helped me grasp the idea of organ on a chip. It is presented in a clear and understandable way with useful pictures and videos. I liked how she ended the talk with the idea that people could have themselves on a chip without making it seem like a bad horror movie.
3) Look into stem cell culture and differentiation of cells in culture. How hard it is to direct this differentiation and what is needed? How can we mimic some of these environments? How undifferentiated do we need these cells to be to make the chip?
Delete1) Mechanobiology is very exciting. Look into **
Delete2) Mike Shuler of Cornell started on this 20 years ago.
Months, hence not good for acute conditions. There are already tests of tumor explants and immune cells.
3) Beyond class.
4) Good.
1) Look into **PIEZO2**
DeleteSysBio16 Asgn_7A_Class_07_TEDx_01_2016_09_15
ReplyDeleteYour body in a microchip
0. KNEW
Knew the concept of OoC and familiar with the innate challenges of cell/tissue engineering and current state of drug discovery (cells -> animals -> humans).
1. LEARNED
Diminishing returns of pharma R&D. I would have expected the opposite because of the advent of new technologies.
2. PRESSING
Describing personalized medicine at the end, where everyone has their own OoC, is she implying that each user would have an OoC with cells derived from their own body? How far are we from being able to take iPS cells and creating something like that? Which cells would you use and how would you obtain them (MSCs, HSCs, fibroblasts? isolate from skin, blood?)
What OoC's have been connected? Do the interactions of OoC's give rise to new cell types (other than what you put into it to start) because of the dynamic interactions between the chips? Do cells dedifferentiate/transdifferentiate in OoC? What kind of microstructures have been created in OoC (cilia, ducts, vasculature)?
3. PRESENTATION
Cell and tissue engineering in the context of OoC
Fabrication methods for OoC
What organs currently exist in OoC form
4. THOUGHTS
Really interested to see how the 'instrument' she describes (plug & play multi OoC reader) develops in the future, and what it is like now.
1) New technologies are offset by the loss of low-hanging fruit.
Delete2) Demonstrated. Our first tests now being started.
OOC connection list 4-10 organs by 4-5 groups.
3) Beyond class, but a good topic.
4) Yes - me too. I will show my SD talk at some point
Natalie Hawken
ReplyDeleteAsgn 7A, TEDx 01: Your body in a microchip - Geraldine Hamilton
0. KNEW
I knew the general process for drug development in the US and the idea that it was very expensive. From my own research, I knew how difficult it can be to work with cell lines and how they often differ in function from in vivo tissue. I knew the basics of the organ on a chip idea from our earlier conversations in class.
1. LEARNED
I learned a lot about how the human cells are introduced into the organ chip. I didn't understand how the chips integrated cells, so seeing the lung cells and capillary cells on the polymer was really interesting. I knew that cells face a lot of mechanical stresses in the body, but I didn't realize how important this mechanical motion was. I also learned a lot about applying organ on a chip technology to personalized medicine.
2. MOST PRESSING QUESTIONS
What are the difficulties of connecting organ chips together? How specifically are they linked together? I understand that fluid flows between the chips, but are the organs connected in a specific order, how quickly does the fluid move, etc?
I assume that the organ chips still aren't an ideal environment for cell health, so how do the cells in the chips act differently than in the body?
Have drugs been used on these chips to see whether or not they mimic human body responses?
3. PRESENTATION TOPIC
Present on the basic mechanics of each organ on a chip. What inputs and outputs are used for the organ and what basic functions of each organ are represented?
4. THOUGHTS
I didn't realize until seeing this video and looking at all of the related video that organ chips are being developed in some many different places. How well can we connect organ chips from different labs together? I thought she was a really good presenter and I enjoyed her talk.
0) Good that you understand this!
Delete1) Good
2) We may read my "Challenges" paper. If not, I can get it to you.
3) Beyond this class.
4) Will show with San Diego talk and a paper coming from one consortium.
0.Knew: I knew about the existence of organs on chips and that they are advantageous in that they allow researchers and scientists to accurately mimic the environment and functionality of the human body without the need for animal testing (ethically controversial) and dish testing. I also knew that the way humanity commonly goes about developing treatments is costly and that it does not prepare well for potential adverse effects to a number of patients or even to a whole population.
ReplyDelete1.Learned: Never have I ever thought of having chip organs personalized with my very own cells. It makes so much sense that personalized chip organs (or chip versions of the people whose cells they contain) would be of use in determining what effects certain drugs will have on specific people. Additionally, I learned about the structure of a chip organ; there is a porous membrane with organ cells on top that are exposed to an air channel, and on the bottom there are capillary cells exposed to a “blood channel” through which nutrients can flow. I also think it was helpful to see how the chip organ mimicked mechanical stresses on the cells.
2.Pressing Questions: In Hamilton’s presentation, we were shown that chip organs exist for the liver, the intestines, the lungs, the heart and bone marrow. Are there any organs/cell types at this point that chip technology has yet to reach? I also found it interesting that she mentioned how organs on a chip can help with clinical trials; how far advanced in clinical research have we gotten this far with chip organs?
3.Presentation: I would like to learn more about the machine with the allegedly easy user interface designed to facilitate the connections of at least ten different chip organs. How does it do this?
4.Thoughts: I appreciated that the presenter made it easy for those not in a scientific community to understand why organs on chips are helpful. I also like that this presentation made the benefits of chip organs personal to the audience and viewers, which is more effective than presenting chip organs as a win for engineers, biologists and other researchers. I am also thinking that personalizing chip organs may reduce drug-related lawsuits.
1) Not all organs look alike, despite the desires of the Wyss/Emulate.
Delete2) List is growing. None really in pre-clinical trials yet, to my knowledge.
3) We will discuss this with the San Diego talk. Geraldine hides lots of details....
4) Lawsuits are another problem...
0 Knew
ReplyDeleteI didn't really know anything about organs on a chip besides what we've discussed in class. I am familiar with cell culture and the limitations of using cell culture to understand biological processes in vivo.
1 Learned
I thought the lung on a chip was very cool, in particular the model of pneumonia and their demonstration of leukocyte extravasation. The idea of a patient on a chip was also interesting, though it wasn't clear to me how useful that would be clinically
2 Pressing questions
If cell culture doesn't mimic the state of the cell in vivo who is to say an organ on a chip is any better? How do we validate these new models? What is the "gold standard." How robust are the hypotheses generated by organ on a chip models?
3 I'd like to learn more about how new biological models are validated. Do we compare them to in vivo models? Are specific functional assays necessary or can more flexible -omics approaches be used?
4 Thoughts
Very excited about the idea of organs on a chip, but I haven't been convinced yet that they should replace cell culture and animals as a model system for understanding biology. The interdisciplinary teams required for doing organ on a chip biology are also inspiring, would love to know more about how roles are divided up and shared between investigators from diverse backgrounds.
I really like your gold standard question; what is the "normal" state of these cells in the body? Will this technology be taken at face value for being a better alternative, yet not ever quantitatively concluded to do so? The ability to apply stress and link the cell lines is certainly novel and so cannot really be compared. Should we accept these capabilities without first validating they are an accurate model of the body?
Delete1) Lung very cool
Delete2) EXCELLENT QUESTIONS - WE NEED TO LOOK AT WEIGHTED GENE CO-EXPRESSION ANALYSIS!!
3) Definitely worthy of discussion. Could do the same for biomarkers ***
4) I agree.
I really like your gold standard question; what is the "normal" state of these cells in the body? Will this technology be taken at face value for being a better alternative, yet not ever quantitatively concluded to do so? The ability to apply stress and link the cell lines is certainly novel and so cannot really be compared. Should we accept these capabilities without first validating they are an accurate model of the body?
Delete0. KNEW
ReplyDeletePrior to watching this TEDx Talk, I was fundamentally aware of the necessity for human cell testing for advanced trials past animal trials. However, the necessity for the conditions of the test human cells to be environmentally analogous to those of the human body presents an engineering challenge. So, for organs on a chip, we need to model the same biochemistry and mechanical strain that would be expected for cells of the same type in the human body.
1. LEARNED
Most of the video provided new information for me. Although in this class thus far, we have talked extensively about modeling the chemical pathways in cells in response to a stimulus, we have not talked to a large degree about the practical construction of an organ on a chip. For example, the porous membrane in the lung microchip has lung cells lining the top exposed to air and capillary cells lining the bottom exposed to artificial blood containing nutrients.
I also learned the functionality involved in the organ microchip, like the ability to model infection in this lung on a chip using infectious bacteria and lymphocytes in the blood, and to be able to capture that in video using fluorescence.
I feel the most important aspect of the presentation is the ability to create networks connecting different organ microchips to model the organ systems of a human, all on microchips. Theoretically, in many cases, we can skip the animal testing phase altogether. Logistically, bodies on a chip can be used to test a variety of demographics, as opposed to current clinical testing only being done in adults, even though the drug of interest may be used on a child, for instance.
2. PRESSING ?
What exactly is the cell selection process? Do we start with stem cells and influence differentiation on the chip, and what does that process entail? What goes into engineering the chip from a biomaterials standpoint, and are these chips designed to be specific to different organ models?
3. PRESENTATION
Cell differentiation, immune response (lots of information crammed into last semester…a lot of that process as left my memory)
4. THOUGHTS
I enjoyed the talk very much. I feel she conveyed the information well without going into the depth of a full blown scientific paper, which is a nice breather.
0) Yes
Delete1) I doubt that animals can be skipped, despite the EU. Specific demographics/genotypes is a good target.
2) ** Cell Sources **
3) We do need **Differentiation 101**
4) Good
. KNEW:
ReplyDeleteI knew about traditional cell and animal testing of drugs. I was aware of the process of developing drugs, including the phases. I knew about the basic idea of cells on chips.
1. LEARNED:
I learned about the actual composition of the lung-on-a-chip. I learned that a huge benefit from organs-on-chips is that physical stresses can be applied which mimic how the cells perform in the body. I gained a greater perspective of how these chips can scale and be connected in systems. I learned about the industrial and research applications of these chips. I learned about the long term goal of making these chips plug and play.
2. PRESSING ?:
How many labs are working on organs-on-chips?
How long can these chips last?
3. PRESENTATION:
I would focus less about the actually design of the chips and more on how these are being used currently, what is being developed, and what has been accomplished with these chips.
4. THOUGHTS:
I liked this TEDx talk. It was very different from the papers that we read but it gave a greater perspective on this technology and future applications. Very thought provoking.
2) Dozens
Delete3) We may get to this late in the semester.
4) Good.
Stephen Lee
ReplyDeleteClass 07, Assignment 7a
TEDx 01 Geraldine Hamilton -- Your body in a microchip
(0) Knew:
Knew about the costs/risks associated with drug discovery, frequency of failure. Knew about efforts to make in vitro cell environments more hospitable and for organs on chips to play a principal role in this effort.
(1) Learned:
I learned about the use of organs on chips to observe non-pharmacological phenomena, such as immune response and ciliopathies. As a corollary, I learned that organs on chips can serve as a tool for drug discovery and disease modeling as readily as drug evaluation.
(2) Pressing Questions:
How physiologically accurate are disease models in organs on chips? Many disease exploit body architecture, and because organs on chips hardly resemble their corresponding organs, this effort may be difficult. How will the development of organs on chips influence the structure of clinical trials? Dr. Hamilton mentions exploring how children respond to drugs, but how readily available are children’s cell lines as opposed to stock adult lines?
(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. (I mention this in my PCRC concerning Dr. Wikswo’s talk as well).
(4) Thoughts:
Dr. Hamilton and Dr. Wikswo presented their work similarly, though Dr. Hamilton went into further detail about specific organs (incl. lung), while Dr. Wikswo gave a broader, more conceptual overview. Given its inherent technicality, both presenters endeavored to engage the audience in ways that would keep them interested in the otherwise difficult material. This was an interesting presentation!
Geraldine Hamilton -- Your body in a microchip
ReplyDelete0. KNEW:
After having already watched Professor Wikswo's talk, I felt like I had heard this spiel before. I already knew the general idea behind organs on chips and wanting something more representative of the dynamic array of connections found in the human body. I also know a lot more biology now than I did when I heard the other talk--in particular, I know some biochemistry and have thought a little bit about drug MOAs.
1. LEARNED:
Dr. Hamilton made me think a little bit oncemore about the details of an organ on a chip. What we're currently trying to do seems a little bit crude; in all honesty, it is probably much more reasonable that we will have (in the short-term) chips tailored to analyzing specific interactions instead of chips intended to emulate every important interaction in the body. I was reminded about putting different cells together on something, and allowing them to 'breathe' and experience other physical stresses.
2. PRESSING?:
How big and complicated a chip do you need to faithfully reproduce the complex interactions happening within the human body?
Here's another one I just thought of: just because interactions BETWEEN parts of the body does not necessarily mean that interactions with EXTERNAL agents will also be faithfully represented. How does one make sure that is also done properly? I get the sense that you really have to get the biochemistry, physical stresses, overall network, etc. right to get this down.
Also, what would getting a personalized organ on a chip entail? How expensive/feasible is that, and in what timeframe? Is this just hype or will it happen in our lifetimes?
3. PRESENTATION:
It would be cool to see the breakdown of a state of the art organ on a chip, with all of its different features pointed out, as well as what is and is not faithfully represented.
4. THOUGHTS:
Watching this talk, I really feel like I have learned something in the past few weeks--between this and the intensive IGP course I am taking. So that's good I suppose.