Build a class list of examples of control IN the GLBA, and what are examples OF external control of the GLBA. Read the comments by your classmates and post a PCRC on the Blog that lists additional 1) Examples of control IN the GLBA. 2) Examples of how one might control the GLBA.
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, November 15, 2018
SysBio18 Asgn_9C_Class_25_List_01_2018_11_27 Control In/Of GLBA
Build a class list of examples of control IN the GLBA, and what are examples OF external control of the GLBA. Read the comments by your classmates and post a PCRC on the Blog that lists additional 1) Examples of control IN the GLBA. 2) Examples of how one might control the GLBA.
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1. Around 90% of serotonin production occurs within the gut. The microbiota play a pivotal role in this production process. Microbiota secretions - primarily short chain fatty acids - are known to increase the synthesis of the enzyme TPH1, the rate limiting catalyst in serotonin production. Through serotonin and other factors, the gut microbiota influence the development and function of the immune and central nervous systems. There is evidence that CNS-induced biochemical changes lead to changes in gut immune system and structure, such as permeability. These changes then influence the development of the microbiota. Clearly, there is a control system at play, though the full extent and mechanisms of this systems are not yet fully understood.
ReplyDelete2. In situ engineering of gut microbiota appears to be a potentially lucrative source of information and medical applications. These methods range from whole microbiota transplants to engineering probiotics. While there is still lots of work to be done in making these methods viable, metagenomic approaches. Changes in microbiota would elicit both functional and genomic changes, which could be measured and used to make new adaptions. While there are many safety issues that need to be addressed, the long-term vision is being able to use pre/probiotics to drive people out of disease-associated steady states and into standard homeostasis.
Blood glucose levels are controlled by the liver. In fasted state, liver is producing ~9g/hr of glucose and releasing to bloodstream. Brain requires ~6 g/hr of this and muscle/fat tissue takes the rest. When you eat, the intestine introduces glucose at some rate (say, 50 g/hr after drinking a Dr. Pepper). The Liver then switches to taking up ~12g/hr of glucose, the brain still takes only ~6 g/hr, and the muscles/fat absorb the rest until blood glucose levels are back to resting level (<110 mg/dL).
ReplyDeleteAlthough I wrote this thinking about a control system WITHIN the MGLBA, this could also be thought of as external control OF the system if you consider blood glucose concentration to be "external". In this way, a single value affects release of insulin, storage/release of glucagon, and localization of cellular glucose transporters (GLUT1-4).
Delete1) One example of control within the GBLA is gut cell differentiation and the regulatory pathways that are involved in maintaining differentiation of the absorptive, goblet, tuft, enteroendocrine, and paneth cells. Notch and Went signaling regulate the differentiation, but once one pathway is chosen, the system utilizes genetic control from genes like Hes1 to inhibit differentiation into the other cell types. Another major example of control is endocrine control of the Gut-Liver-Pancreas-Stomach axis. For example, if the pH of the duodenum drops, then there is positive feedback on the release of bicarbonate from the pancreas, but negative feedback on gastrin in the stomach.
ReplyDelete2. One way in which we could possibly control the Gut-Liver-Pancreas-Stomach axis is through the introduction of particular Fatty acid metabolites that would stimulate cholecystokinin release and therefore bile release. In addition, in the relationship between the stomach and the duodenum, pH regulates a lot of the different enzymes and cells (parietal cells and chief cells). pH control is one chemical input that could be used for external control of the expression of these genes to produce various enzymes involved in digestion. A way we could possibly control stem cell differentiation from an external side is if we ourselves control the introduction of epidermal growth factors that stimulate stem cells to differentiate in the gut. Chemical and genetic inputs could serve a strong purpose in control of both gut cell differentiation as well as the stomach-gut-liver-pancreas axis.
1: CYP1 is the rate limiting enzyme in bile secretion in the Liver. In the gut, bile is converted by microbiota, in particular Bifidobacterium and Blautia. Blautia has an effect on TPH1 production which is the rate limiting enzyme for 5-HT production.
ReplyDelete2: Bile secretion can be limited by inhibiting BSEP activity but can lead to toxic effects and is often associated with DILI. CYP1 and TPH1 control through growth factors and controlling the number of Bifidobacterium and Blautia can affect 5-HT production since they are upstream.
BMP2 is a growth factor that promotes Mash1, Hes5, and Id1 which are interconnected with Hes1 in neuronal cells. I am unsure the extent to which this would work in the gut but it is a potential lead. Nrf2 can affect Notch signaling and how the cells are plated will significantly affect Notch signalling due to the spatial nature of its expression.
Mechanotransduction affects integrin signalling and would be useful for optimizing the cell culture growth for a given organ.
Infrared laser pulses can be used to selectively trigger neurons which is preferential over electrical simulation since there is an associated leakage with it.
Media can be used to optimize culture growth and alter the composition of the microbiome. Antibiotics can be used to induce stress in the microbiome.
1. The epithelial layer that separates the intestine lumen from the loose connective tissue. The enterocytes in the intestine epithelium are replaced every 3-5 days to remove infected and damaged cells.
ReplyDelete2. Mucins, the major component of mucus, are secreted by goblet cells. The mucus layer is a physical barrier to to pathogens. A cytokine called IL-22 stimulates goblet cell generation and thus mucin production. So mucin production can be controlled by controlling IL-22 production.
Controlling the amount of IgA secreted affects the microbial community and consequently the adaptive immune response.