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.
Thursday, October 18, 2018
SysBio18 Asgn_7B_Class_17_Article_06_2018_10_23: Gut-Brain Review-2
Gut-Brain Review: Read Article 05 E.E. Mayer, "Gut feelings: the
emerging biology of gut-brain communication," NatRevNeuro, 12: 453-466
(2011) . Post a PCRC on the Blog. We need a volunteer to moderate the blog and guide the discussion of the blog postings!
Subscribe to:
Post Comments (Atom)
This comment has been removed by the author.
ReplyDeleteThis comment has been removed by the author.
Delete0. I am pretty familiar with the experiments that looked at germ-free mice, as I have seen it through my lit review of serotonin metabolism and we have also heard about this model in a class presentation. I have background knowledge on brain development.
ReplyDelete1. I did not know much about how the microbiome develops in the body. It was interesting to read about how the microbiome can impact brain development. I have read about ASD being associated with an atypical microbiome, but I had not seen anything connecting the microbiome to schizophrenia.
2. Are there any microfluidic models of the microbiome that have been developed? Do we need the ENS to model the gut-brain axis, or is it enough to have the microbiome and brain represented?
3. A presentation that tracks the development of the ENS and maybe the GI tract might be useful.
4. I like Figure 2, but I think it also needs a section where it describes the development of the ENS (as well as maybe the parasympathetic and sympathetic nervous systems). Additionally, for our background and significance sections of the final project, it might be useful to come up with limitations to using animal models (and/or current in vitro models) in order to justify why a gut-brain axis on a chip is a compelling project.
0) KNEW
ReplyDeleteI knew the basics of the CNS, as well as the idea of gut microbiome diversity.
1) LEARNED
Neurogenesis, apoptosis, and synaptic pruning may be regulated by signals from the microbiome.
"PG can cross the placenta and reach the fetal brain, where it induces proliferation of neurons in the frontal cortex via increased expression of FOXG1, a critical regulator of forebrain development and neurogenesis. Offspring exposed to PG prenatally exhibit decreased cognitive function" (919).
Neurogenesis can be promoted by serotonin.
I also learned a good bit about how some diseases are manifest in the gut/microbiome, specifically relating to lack of microbiome diversity.
I learned a bit about the overall development and degradation of neurons.
2) QUESTION
How might we intentionally include apoptosis (or autophogy @Joey) into our chips?
3) PRESENTATION
How does the G-B axis form, developmentally
4) THOUGHTS
I thought this paper explored a lot of topics well. I think that it will be helpful to comb through some of the references to see how they relate to disease or development. Also, the paper focused more on how the gut affects neurodevelopment. Do we have an analogous of how the brain affects gut/microbiome development?
0) What I knew
ReplyDeleteI am pretty familiar with some of the basic neurobiology they discuss, specifically the developmental neurobiology. I am familiar with some of the concepts like gastrulation, the development of germ layers, neurogenesis with neural crest cells, and processes like synaptic pruning with the aid of astrocytes and microglia.
1) What I learned
This article taught me a lot about the specific role the microbiome plays during the development of the human. For example, it was really interesting to learn that our blood-brain barrier's permeability degree is influenced by microbial metabolite concentrations. In addition, it was really interesting to learn that maternal microbial levels and diversity, especially in the womb, can influence the behavior and development of the offspring. Finally, it was interesting to learn the peptidoglycan, a key component in some bacterial cell walls, can cross the placenta and proliferate neuron development in the frontal cortex in the fetal brain.
2) Question:
For the GBA on a chip, how could we simulate fluctuations in microbiome composition due to dysbiosis? Furthermore, how could we use the microbiome on our GBA on a chip as a marker of a disease/normal state (for both gut and brain)?
3) Presentation
Glial Cells and their role in the Enteric Nervous System
4) Thoughts
I thought that this paper was nice in that it presented a very holistic analysis of the role of the microbiome in the development of the nervous system. It focused a good amount on the role of the microbiome in developmental biology, which I think is helpful in understanding the integral role of microbiome in our general physiology. I think it would be helpful to look more into how the immune system's development interacts with the microbiome, as that may be a key interaction for our GBA on a chip.
0. The microbiome important for the GBA and it develops over time since babies are initially sterile.
ReplyDelete1. The microbiome includes more than bacteria and can also include archaea, fungi, and viruses. The microbiome has a large impact of the development of the BBB, neurogenesis, gliogenesis, myelination, and neuron differentiation signaling (specifically BDNF). The adult microbiome is roughly in steady state and is dependent diet, lifestyle, geography, and genetics. A healthy microbiome tends to be diverse. Diseases are associated with disruption of a healthy microbiome either during development of from the adult steady state.
2. Should we focus on disease during development or during adulthood?
3. What the microbiome usually consists of. How do the ratios of bacteria, archaea, fungi, and viruses compare?
4. This article does a good job showing the different roles the microbiome can play, especially for development. The large effect the microbiome has during development will be critical for thinking about disease and inform our modeling of it.
The Central Nervous System and the Gut Microbiome, Sharon, et al. (2016)
ReplyDelete(is this the right paper?)
0) I am familiar with microbial colonization during development and its importance to the GBA from other reviews in this class. The experiments with GF mice were also familiar.
1) "Importantly, the healthy microbiome is temporally stable, even when subjected to recurrent mild disturbances (Dethlefsen et al., 2008; Oh et al., 2016; Schloissnig et al., 2013). Decreased diversity, or lack of redundancy, in the microbiome has been reported in multiple diseases." A stable microbiome is important.
2) When modeling this system in a chip, how can we ensure that the microbiome is as stable as it needs to be for healthy homeostasis in vivo? Especially since the associated disease states are longitudinal or impossible to measure in a chip (i.e. depression), how would you know that your gut-brain-axis-on-a-chip is healthy?
3) This paper was very clinical, and most of these pathologies are behavioral/psychological, and therefore impossible to measure in vitro unless reliable biomarkers are developed. What disease states, if any, could be modeled and measured on a chip, taking into account temporal effects and pathophysiology?
4) This one had pretty figures. It was extremely light on molecular interactions and provided a broad overview of psychological pathology related to microbiome diversity.
0.) What I Already Knew: Very little about brain development.
ReplyDelete1.) What I Learned: Neurogenesis is increased in GF mice in several brain areas. The Enteric Nervous Systems deteriorates with age.
2.) Questions: How do microbiota signals travel during development? Is there a different microbiota within the fetus and, if so, which is more impactful - that of the fetus or the mother? Is the developmental microbiota the most impactful?
3.) In-Class Presentation: Neurogenesis.
4.) Other Comments: I am a bit confused by the discussion on the impact on neurogenesis. GF mice see increased activity but anti-biotic treated mice see decreased? On a different note, if there exists a proper/ideal microbiota, what would be the best method of implanting this in an individual? All of the papers we have read indicate that a wide variety of conditions and developments can be linked to the microbiota. How do we determine which of those are significant?
Additional presentation subject: microbiota engineering
Delete0) What I already knew
ReplyDeleteEmerging data suggest communication between the gut and the brain in anxiety, depression, cognition, and autism spectrum disorder (ASD).
The gut microbiome plays a role in basic neurogenerative processes such as the formation of the blood-brain barrier, myelination, neurogenesis, and microglia maturation and also modulates many aspects of
animal behavior.
1) The most important think I learned
Many major processes in neurodevelopment coincide with changes in the maternal and neonatal gut microbiome
prenatal brain development.
Some diseases like child autisim failed to generate a coherent picture.
2) My most pressing question from the reading
The article mentions many studies which have demonstrated that different bacterial populations are associated
with certain clinical conditions. However, is it possible that the changes in microbiome doesn’t fundamentally account for the disease itself? If so, how can the study of microbiome be helpful for determining underlying causes?
3) A suggestion for a class discussion
Neuroinflammation and microbiome
4) Any thoughts that you might have on the class or paper
I think this paper comprehensively summarized the role of microbiome in GBA and how it’s relevant to many CNS diseases. Since gut microbiome is still not thoroughly understood, it may not be worthwhile to include too much details/roles in our GBA model.
The gut microbiome affects the immune system.
ReplyDelete1) What I learned
The gut microbiome affects emotions and well-being of the host. Neurogenesis is influenced by the presence of microorganisms. Certain bacterial populations are associated with certain clinical conditions. We do not know if these differences are causative or promote disease.
2) Most pressing questions
How do we efficiently test if certain gut bacteria cause disease? There are many test we could run, but what is the best way to do this to further knowledge on the gut-brain axis?
3) Presentation topic
How can we quantify mental health or neurodegenerative disorders, such as autism and schizophrenia? If we had a way to measure mental health and it was in our health care system, how would this affect what jobs people get and how they are viewed in society?
4) Thoughts
It is interesting that germ-free animals have reduced anxiety…I wonder how much the environment affects anxiety and levels of dopamine and serotonin. I am interested in how biochemical pathways and levels of hormones affect mental health.