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.
Juan Gnecco
ReplyDeleteAsgn_2B/Article 02
0. Knew: That microfluidic devices i.e. organs on chips can be used as a model to apply reductionist information in a constructionist form. Also, knew how complex biology is because of its dynamic nature.
1. Learned: what hermeneutics is, how philosophical it is and how it can be applied to biology. Also the definition of function through biology and physics - the differences and similarities.
2. Pressing: How can function be determined by applying biology and physics and how simple can get define a model without making it too simple.
3. The idea of reductionism and constructionism to go from top-bottom and bottom to top.
4. Severely complex, but as explained it is a matter of crating a simplistic model that opens new knowledge without getting lost in information. Good and profound intro to the topic.
Nate Braman
ReplyDeleteAssignment 2B/ Biology Coming Full Circle
0. Knew: The concept of OoCs, the different levels of biological organization, the idea of emergence in ascending levels of organization
1. The term "hermeneutics" and the hermeneutic circle of biology. Convergence in OoCs and its importance. The idea that biology can't be understood with simply a reductionist or constructionist approach - it requires many iterations of investigation across different organizational levels.
2. Pressing ?: What are the trade offs of modeling biological systems with greater accuracy? Is an increase in complexity at a lower organizational level amplified across higher orders? How can we determine what details of a model are "both necessary and sufficient?"
3. Presentation: The various levels of biological organization that encompass an organism are complex and interwoven. In order to more completely understand and model biology at any given organizational level, it is necessary to place it within the context of the full biological hierarchy - affecting and affected by both its parts and the systems encompassing it.
4. Thoughts: This article really gave a great sense of how intertwined the hierarchy of biology is and how these problems tie into OoCs. It seems that a multitude of approaches and perspective are needed to tackle large biological problems, such as OoCs.
James Pino
ReplyDeleteAssignment 2B
0:Knew: The hermeneutic thought process of biology. Reductionist rational.
1:Learned: A lot of history of reductionist thoughts and found some interesting quotes about model systems. The diagram of herneutic circle of biology and that we are not to the point of traveling back up in scale.
2:Pressing?: With the knowledge we have now from the reductionist methods and the power of modern computers ( and as computer continue to progress) will it be possible to construct valuable models based on first principles, or do we really need each part in the whole or among other parts? The advent of life didn't know the emergent properties or require the history that lead its modern standard. Did life lose these principle properties throughout evolution in such a way that we can not reconstruct life based upon what we know it as today?
3:Presentation: Providing insight into modern biology and the complexity of its study. Gives reasoning behind the future of OoCs and their role in our understanding of life.
4:Thoughts: I am glad I am alive at such an exciting time where we begin the upward path of understanding life. I have a fascination with the protein folding problem and almost decided to spend my graduate career (and probably life) working on this problem. I am becoming more satisfied with my choice in studying the bigger question addressed in this article.
Kate Jones
ReplyDeleteAssignment 2B
0: Knew: I knew of the concept of the hermeneutic circle and the relationship between understanding the whole to understand the parts and vice versa. I also knew that that organs on chips try to incorporate the interactions between cells and external environments, mechanical forces, and electrical signaling.
1. Learned: I learned that the ideal complexity for these models is simple enough to be helpful and worthwhile yet complex enough to produce emergent properties such as organ-organ interactions leading to unexpected effects of drug metabolism.
2. Pressing ?: How do we know when the model we have created is complex enough for use as a general model for drug metabolism. The model may be complex enough to show one type of organ-organ interaction, but what if a more complex model would show an important alternative interaction that would change the action of the drug?
3. Presentation: An important topic is modifying the devices once we go around the hermeneutic circle and learn more and more about the body and its chemistry.
4. Thoughts: This article showed me that my concerns and questions of complexity and modeling without knowing all of the information are a main concern and really the reason why organs on a chip are useful in simplifying the body.
Selene van der Walt
ReplyDeleteAssignment 2B
0. Knew: The basic concept of a Hermeneutic circle (from reading the article for assignment 2A)., and the concept of emergence as applied to biology.
1. Learned: The importance of defining functional boundaries to distinguish the parts of an organism and about post-reductionist thinking when attempting to model the human body.
2. Pressing ?: When using OoC technology to test for adverse drug reactions with several organs being linked on the same chip how easy is it to determine which organs interacted and were the source of the adverse reaction?
3. Presentation: The importance of the post-reductionist approach when modeling the human body.
4. Thoughts: The concept emergent function in biology is very interesting and definitely something that will be difficult to effectively simulate in engineered models of biological systems.
0. Fundamental processes and design of OoC and bioreactors.
ReplyDelete1. It was astounding to learn the abundance of variables associated with the technical challenges for successfully establishing a MPS.
2. Pressing: With environmental factors constantly changing the molecular makeup of humans, how do we design homunculi to evolve with our ever-evolving environment? Will the homunculi ever truly represent the average, living human who has been exposed to environmental toxins, whether man made or organic, for the majority of their lives?
3. Presentation: Provides a look into the experimental structure associated with creating and maintaining OoC
4: Thoughts: This was a very well written article in that it takes a novel topic and breaks it down for the lay person. I also thought it was beneficial to be able to see the myriad of scientists and research centers working in collaboration towards a common goal. It is proof of how far science and the scientific method have expanded over time.
Kendra Oliver A02/ Biology coming full circle: Joining the whole and the parts
ReplyDelete0. Knew: Studying “parts” of a whole (ie a cell removed from its endogenous environment) does not inform us of its endogenous function. This reductionist system is only describing the “part” based on its contextual environment. The study of “parts” in biology has been explored in great detail and is the basis of much of our current physiology/signaling knowledge, but limitations arise based on the differences in context once related back to physiological environment.
1. Learned: A very interesting point made in the article is the distinction between biology and physics; in particular that the idea of coping that solely defined in a biological system. To study biological systems most of current science has primarily used a reductionist approach. It is interesting to but into a philosophical context the reductionist versus constructionist (Anderson’s) methodology. For constriction you need to address function, integration and construction. In addition to this complexity found in biology, it is also required that genetic alterations that can occur based on genome are included when designing the system. Most interesting is the idea of a toy model for system biology. The idea of a toy model would be to acquire intuition about a system rather then reconstructing the endogenous system to its complete perfection. Finally the convergence in biology is tested if the parts equal the whole but with all the complexity mentioned, this may be a difficult endeavor.
2. Pressing ?: Do organs on a chip relay on assumptions made from inaccurate cellular systems? How closely does the synthetic system represent the full system? Going back to the idea of hermeneutic circle how do we choose to define the closed system?
3. Presentation:
4. Thoughts: Could we articulate the historical context of the cell (ie. genome historical architecture) based on the context, especially within a particular pathology? Will closed loop controls of immortalized or constructed cell types arise to the same non-physiological relevant conclusion as current cellular systems? How does one articulate a specific question in systems biology and MPS?
0. Knew: To understand the whole of something you must understand the parts of it.
ReplyDelete1. Learned: The journal of Experimental Biology and Medicine changed its cover.
2. Pressing ?: If you removed Ooc related items from the circle, could you not argue that we have already made at least one trip around the circle?
3. Presentation: A somewhat romantic explanation of the thought behind the new cover of Experimental Biology and Medicine and the future of multidisciplinary medical science.
4. Thoughts: Has there been a better time to be part of the medical sciences?
Arman Chowdhury
ReplyDeleteAssignment 2B
0. Knew: Over the past 2500 years, physics, physiology and biology have been highly reductionist, with the goal of finding the most fundamental particles, interactions, or information. Today, we can readily explore what may be the reductionist limit of biology- the rapid sequencing of the genome of an individual human and a myriad of other organisms. Mathematics can provide biology with rigorous predictions that can be tested quantitatively in a controlled, reproducible setting.
1. Learned: Hermeneutics is the study of interpretation and meaning, originally of texts, and the basic principle of the hermeneutic circle is that “one cannot understand the whole until one understands the parts, and one cannot understand the parts until one understands the whole.” At the level of biochemistry, function means the reactions that matter in vitro have to be sufficiently like the same reactions in vivo. Function in biology is an emergent behavior of an ensemble of different molecules – a collective behavior that is not readily predicted from knowledge of the behavior of each individual molecule. In a normal environment, were the cell normally to interact only with the surrounding fluid medium, then recapitulation of that microenvironment would simply require matching the chemistries and flows. If the cell had mechanical interactions with matrix or neighboring cells, reconstructing the boundary would be much more complicated, in that stresses and strains would need to be controlled. The hermeneutic circle of understanding is an iterative process.
2. Pressing ?: Again, the question is whether organs on a chip can realistically approximate the complexity of centuries of evolution of human physiology.
3. Presentation: The mini review article focuses on the hermeneutic circle of understanding biology, and talks about hermeneutics, function, exploring reductionist limit of biology, and finally concludes with the prediction capabilities of mathematical modeling in regards to biology.
4. Thoughts: The review article describes the theory behind organs on a chip and talks about hopeful prospects and opportunities, and I personally agree with the article and think more research should be focused on this iterative process of modeling human physiology.
Tim Lee
ReplyDeleteAsgn_2B/Article 02
0. Knew: Concept of understanding the whole from its parts
1. Learned: The term of hermeneutic circle and our new approach of understanding our parts to be able to build them up for specific functions we need.
2. Pressing: The approach to understanding the whole from the parts sounds very reasonable but doesn't the model seem too linear? Especially in regards to the Organs on a Chip project, shouldn't the model try to convey the interactions between multiple parts to make a whole part?
3. Presentation: The idea behind the hermeneutic circle and how it applies to biology and medical sciences.
4. Thoughts: This article helped me think about the fundamental way in which we approach human biology. It seems that function is the most critical part about what we are concerned with and understanding the whole from its parts is really meant to help us manipulate the knowledge to get the functions we need.
Mark Vander Roest
ReplyDeleteAssignment 2B
0. Knew: The concept of simplification and current practices that make use of this idea.
1. Learned: A lot of the history of reductionist strategies and great quotes about reduction/construction biology.
2. Pressing Q: Is there a proper direction of travel around the hermeneutic circle? ie. to realize OoCs, should we build up from a cellular understanding or down from the organ level? There's obviously a need for elements of both, but is one dominant?
3. Presentation: The hermeneutic circle concept of biology, review of reductionist biological studies, constructivist possibilities in biology.
4. Thoughts: This article gave me a bigger picture and helped me realize that we might be starting to hit the limits of the reductionist strategy of biology.
Cameron Togrye
ReplyDeleteAssignment 2B/ Biology coming full circle
0. Knew: The trend towards reductionist biology dominating the landscape for most of the field's history.
1. Learned: The engineering of biomolecules which can control the cell and cell tissues which simulate the actual microenvironment of the tissue provides the ability to traverse the hermeneutic from the most basic genomic level back to the original organism.
2. Pressing: Once again, I am compelled to bring up the question of whether OOC's would bring about more uncertainties than answers. In the traditional, plate cell cultures the interactions were typically very simply (drug-cell interaction) whereas in OOC's these complex inter-organ interactions would potentially be so complex that we might not know what to look for (and if we found it, would be know what it meant?).
3. Presentation: An overview of the milestones in the reductionist (and constructionist) efforts of biology/and or physiology.
4. Thoughts: I thought the notion of biology being the first science (as opposed to physics and chemistry) in which the things being studied had a "stake" in living. Whereas elementary particles and their constructs simply operate according to natural laws as phenomena, biological molecules and their constructs carry out what we view as functions with purpose.
Cami Johnson
ReplyDeleteAssignment 2B/Article 2
0. Knew: Most past research has been dedicated to breaking the animal down into smaller and smaller parts to study. Cell culture in petri dishes has been useful in this reductionist view, but for further advancements, other methods may be necessary.
1. Learned: Organs-on-a-chip could contribute to a newer approach to research, that of construction instead of reduction, and help complete the first hermeneutic cycle. In biology, this constructionist viewpoint is not just about understanding the parts in order to understand the whole, but it is about understanding the function of each part and how they are integrated together.
2. Pressing ?: How far down the left of the cycle do we need to go before we can return back up the right? How many parts should the organism be separated into before it's sufficient? Essentially, have we gotten as much information as we can from the reductionist approach already?
3. Presentation: The article discussed how the reductionist approach has been most widely used and how organs-on-a-chip could contribute to a constructionist approach, and therefore, maybe complete the first cycle of the hermeneutic cycle.
4. Thoughts: This article made me think more deeply about how we approach research and the true, but seemingly oxymoronic, concept of understanding the whole in order to understand the parts, but needing to understand the parts in order to understand the whole. Such a shift in approach may definitely be necessary for more advances.
Shuaipeng "Jimmy" Zhang
ReplyDeleteAssignment 2B/Article 2
0. Knew: The attempt to understand an organism by studying its constituent parts.
1. Learned: An alternative approach to reductionist biology, which is termed "construction". This involves the creation of biomolecules and tissues which have specific functions, which allows for the study of their interactions.The role that OoCs plays in this research.
2. Pressing: Towards the end of the article, a statement is made that "models become particularly interesting when they are of sufficient complexity that they can produce emergent phenomena". Obviously, building these "sufficient complexity" models would require great knowledge of the parts (knowledge obtained through the reductionist approach). How do we know that this level of complexity is reached? What if incorrect emergent phenomena are observed from a lack of full knowledge?
3. Presentation: The reductionist approach was first discussed, supplemented with brief historical notes as well as quotations from notable scientists. An alternative method to studying biology was proposed, construction, and the use of OoCs in this new approach discussed.
4. Thoughts: The "one cannot understand the whole until one understands the parts, and one cannot understand the parts until one understands the whole" viewpoint of hermeneutics was very thought provoking. While past attempts to understand something by breaking it down has yielded astounding results, those results do not predict the function of the parts and their interactions as a whole. These interactions and "emergent phenomena" are ultimately what make biology so mesmerizing and complex.
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