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) What I already knew
ReplyDeleteI watched this TED talk last year when I was in your class, so I remember most of the concepts you brought up.
1) The most important think I learned
I think it was nice to get a reminder that our organs talk to each other. It is kind of easy to forget this sometimes, especially when a lot of my research focuses on the cellular and tissue levels. For example, I think about how my neurons interact with each other and the hydrogels they are embedded in or how astrocytes might interact with brain microvascular endothelial cells, but I don’t normally think about things like the gut-brain interactions. However, the gut-brain axis is important and may be relevant to when I start using my models to study diseases.
2) My most pressing question from the reading
How do you work problems with communication when working with people across disciplines. For one of my projects, I kind of serve as an intermediate/translator between a mechanical engineer and a biologist, but sometimes it feels like some concepts or problems are difficult to properly explain between the two disciplines. Is this something that you improve at with more experience?
3) A suggestion for a class discussion
I think it would be interesting to have a class discussion or presentation on examples of gut-brain interactions and examples of how these interactions are clinically relevant. This may be useful in helping us have a better understanding of the significance of studying this topic, which may also help us later when we work on the class project.
4) Any thoughts that you might have on the class or paper
I always think it’s interesting to hear about organs-on-a-chip studies.
0) What I already knew
ReplyDeleteI was aware of organ-on-a-chip research moving toward models of entire organisms for drug metabolism studies.
1) The most important think I learned
The seemingly endless dimensionality of biological processes require modeling beyond the silos of tissue- or organ-level interactions.
2) My most pressing question from the reading
What are the pitfalls of a homunculus as described in the video, and how do they significantly differ from an animal model? Just as a mouse "system" may differ from a human in drug metabolism, wouldn't a homunculus built from human cells still fall short of a model that is extensible to all humans? How might such models be used when thinking about precision or personalized medicine?
3) A suggestion for a class discussion
We could discuss different organ-on-a-chip models, how they were developed and how they work individually, to get a better idea of how one could link them in series to build a "homunculus".
4) Any thoughts that you might have on the class or paper
I like the idea that studying functional body systems cannot be done in silos, and a birds-eye view of the entire phase space is required to properly predict interactions in vivo.
What I already knew:
ReplyDeleteThat Cellular heterogeneity exists within/between cells and organs. The increasingly interdisciplinary narture of modern biomedical research.
The most important think I learned:
The benefits of using Homunculi and Organs on Chips. That can model drug interactions, cross-talk and chemical modification through multi-organ systems. As well as that knowledge from many different fields are needed to solve these problems at once across many different fields. And to think about things across many different dimensions.
My most pressing question from the reading:
How to go about thinking about things across many different dimensions when these phase space can be very dynamic and non-linear in nature?
A suggestion for a class discussion:
How can Homunculi be made to include computational models of the different levels of biological phenomena within and between organisms (i.e. Chips for single organisms and multiple organisms interacting)?
Any thoughts that you might have on the class or paper:
How does one do analyses in phase space when there are heterogeneity existing within cells and organs that might be functionally relevant to issues at hand with organ-on chip?
0) What I already know
ReplyDeleteOne topic in this video that I have learned about before is the complexity of the gene-gene interactions in the development of the human, though it was really interesting to see this material through the lens of the phase-space graph. In Genetics, we learned a lot about the different ways genes are regulated from bacterial operons to eukaryotic enhancers. The phase-space graph was interesting because it really emphasized the simultaneous character of all 20,000 genes occupying different yet interacting roles in the human body.
1) The most important thing I learned
The most important thing I learned in this video is the interacting disciplines that coalesce to define the organ-on-a-chip research projects that many universities are working on. I was really fascinated by the different examples of scientists like Feynman and Fermi and where they lie on the phase-space graph of intellectual disciplines like physiology, engineering, and physics. Though a majority of people know da Vinci for his status as a Renaissance man, it was really interesting to see his unique position on the phase-space graph of intellectual disciplines and visualize his unique role in mastering all three of these crucial academic disciplines, bridging an intellectual gap at his point in history. Overall, I am really amazed by the interaction of these three disciplines in designing a homunculi-on-a-chip, and how anatomy, engineering, and fluid dynamics can simulate something as complicated as the liver while interacting with other organs.
2) My most pressing question from reading
One of the main questions I had after watching the video is: What is the general procedure by which researchers take a human organ, model its behavior, and transcribe its function into a chip? Though I felt like I understood the general principles of the Athena research project, I really want to learn more about how fluid mechanics and electronics can physically recreate a mini-human organ and act like a part of the human body.
3) Suggestion for Class Discussion
I think a really cool topic for class discussion would be to discuss how the organ-on-a-chip, specifically for a heart, could be used to do a comparative anatomy study of the different chambered hearts of organisms like fish, reptiles, and mammals. In zoology, we talked briefly about how organisms like crocodiles can use cardiac shunts to channel blood away from the pulmonary circuit to conserve oxygen and reduce pressure in the lung, and I think it would be really cool to see if we could apply some of the principles used in designing a heart-on-a-chip to model the hearts of different organisms. We could also compare the 2-chambered hearts of fish to 3-chambered hearts of reptiles to mammalian hearts.
4) Any thoughts on class/paper
I am really excited to learn more about the gut-brain axis and how these two facets of the human body interact. I think it is fascinating how these areas of the body have the same genetic base, but through different expression produce machines with unique functions that influence one another's behavior. I am also really excited to learn about how bacteria in the gut influence the human body through signaling.
0. Knew:
ReplyDeleteThere are efforts underway to develop culture systems that better mimic human complexity by emulating aspects of the microenvironment and enabling crosstalk among modules representing various organs. These types of endeavors require the integration of ideas and talents across several disciplines in order to be executed well.
1. Learned: I was reminded of the overall scope of the homunculi project/concept. I had also somehow forgotten about the organ on a chip at the end, lol.
2. Pressing ?: What are the current limitations of this research?
3. Presentation: Current state of organ on a chip research
4. Thoughts: Dimensions are interesting concepts to me; we bin observations into them and use them to represent a single variable or set thereof, though they are actually the tertiary product of multiple orders of complexity and scale interacting as a whole.
1. What I already knew: there’s a need to understand how a drug/chemical will react with the entire body, not just the target organ
ReplyDelete2. The most important thing I learned: homunculi can effectively simulate organ-organ interactions before human testing occurs by reducing organs to their basic functions
3. My most pressing question: specifics of organ on chips- is it possible to stimulate a nervous system in addition to circulatory system, what kind of testing tells us whether the organ is functioning correctly
4. Suggestion for a class discussion: can we ever actually understand the phase space of a disease or condition or is it too complex
5. Thoughts on the talk: really interesting look at phase space and organs on a chip
ReplyDelete0) What I already knew: I strongly agree with the idea that knowledge overlaps...As an artist (I grew up dancing), I have always wondered why people put themselves in boxes and therefore limit their potential. We aren't bound by our field of knowledge, everything, such as science and art, is related.
1) The most important thing I learned: To build something complex, you have to be able to move across disciplines.
2) My most pressing question: How do biology and physics intersect? What is biophysics?
3) A suggestion for class discussion: How do we be creative as scientists and engineers, and what does it mean to be creative in science versus art? Is "creativity" the same concept in every field?
4) Thoughts
I really liked that Dr. Wikswo said that true creativity is to not discourage imagination by putting people in a silo. I used to think that I had to choose between viewing myself as a scientist or engineer or an artist, but as I grew older I realized that I could be both. I also admire Leonardo Da Vinci because he was a doctor, scientist, engineer, artist...of course he was a very talented genius, but I think he is an example of someone who didn't limit himself by putting himself in a silo, and instead decided to learn as much as he could in whatever subject he wanted.
0.) What I Knew: I have watched this talk a couple times in the past. Systems Biology and technology such as organs on chips created "Homunculi"--miniature humans. These will aid in drug testing and development. However, the human biology is incredibly complex. Somewhere on the order of a mole of differential equations would be needed to create a network of all its functions.
ReplyDelete1.) Most Important Thing I Learned: Analyzing organ systems by themselves leaves out the wealth of interactions between systems. In addition, the expression of a gene varies by organ and even through the interactions between systems of organs.
2.) Most Pressing Question: In designing an organ on a chip, how does one choose which abstractions/simplifications to make?
3.) Suggestion for Class Discussion: I would like to discuss the above question. From the paper we read in preparation for class we know that there are 5 pseudo-categories of Systems Biology. How does on pick and choose elements of these categories in making an organ on a chip?
4.) Thoughts: I liked the swing demonstration of phase space. On a tangent, the term homunculi makes me think of Faust.
I definitely agree with your point that while an organ on a chip is really effective, to truly model a human biological system is a daunting and intense task! I also really like your description of a "mole of differential equations" in reference to the magnitude of modeling required to simulate a biological organ/system.
DeleteFor Video:
ReplyDelete0) What I already knew
Human bodies are very complex and many organs communicate with each other through cardiovascular system. Organ on a chip can be used to test drugs.
1) The most important think I learned
Homunculi has the potential to fill in the gap between mice and human in developing drugs. It can be approached by building/modeling different organ chips and interconnecting them to simulate human bodies. The core idea is to simplify a very complex system into a simple one (model or miniature).
Scientists or intellectuals can exist as different phases (i.e. physicists & engineer & biologist).
2) My most pressing question from the reading
How exactly can one determine the organs to be built on chips for homunculi to work?
Would organ chips output exactly the same for given drugs as the real organs do?
How can more than one organs be interconnected to each other as organ systems do?
Is it possible to build a standardized homunculi for the vast majority of drugs tests?
3) A suggestion for a class discussion
Discuss the possibility to build a full Homunculi and what organs might be involved.
Discuss the skills/abilities/phases required to build a homunculi.
4) Any thoughts that you might have on the class or paper
The future of organ-on chip may be homunculi, may be not. It’s possible that with more advanced drugs the more organs are involved in which ultimately it’s too complicated to build a useful system (output may not be realistic ) or the cost is extremely high.
0) I knew about phase space and homunculi already. From my experience with Dr. Wikswo's class last year, I was introduced to organs on chips
ReplyDelete1) It is very important to avoid silo-like thinking if we are to progress in complex fields, especially in the medical fields
2) What's the next more important (or easiest-- and this is probably quite different) step we need to take in order to reach full approximations of humans on chips? What's the limiting factor right now in connecting more organ systems on chips?
3) How can we encourage multi-tasking/cross-discipline talk within our different classes?
4) Overall, I enjoyed watching this again, especially coming at it with the perspective of knowing Dr. Wikswo for a year and having taken a class on related subjects.
Blog Harvested - will go over comments in class.
ReplyDelete### 2013 TEDx Nashville talk - John Wikswo
ReplyDelete0) What I already knew
I watched this video last year so I recall the intriguing introduction to
phase space via a swinging demonstration.
1) The most important think I learned
Looking at different systems with the same method - using phase space diagrams to describe a dynamical system of swings, system of complex organs, genetic information.
2) My most pressing question from the reading
How do the connections between the organs on a chip work? How exactly are messages passed around so that the organs can 'talk' to each other?
3) A suggestion for a class discussion
Information storage and processing - fundamentals of information theory. How are information stored and passed around in a living system? How do certain cells know what to do at certain time?
4) Any thoughts that you might have on the class or paper