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.
Cameron Togrye
ReplyDeleteAsgn_25A / Article 21: Reconstruction of cellular signalling networks
0. Knew: That FRET was a tool that could be used to determine changes in the proximity between various proteins (including subunit-subunit interactions). Also knew about the fundamental interactions in many of the pathways listed including: JAK-STAT pathway, EGF-Ras-MAPK pathway, and Wnt Pathway.
1. Learned: It was interesting to learn that such a large percentage (40-60%) of genes allow for alternative splicing events, and that the average protein has 2.5 PTM variants. Hearing this (while also being aware of the numerous functions of much of the 'non-coding' DNA) helps rationalize how our genome (only about 20,000 genes) was so overestimated when the human genome was first being characterized.
2. Pressing: The paper makes a point to illustrate that the number of functional states outpaces the number of components in these biochemical networks. Why then, is the norm in these networks to have so many "combinatorically superflous" components? Would the most efficient route in evolution be to fully utilize the numerous functional states that alternative splicing and PTM's give you? Also, later in the paper, it is stated that regulatory patterns observed in expression arrays for genes controlled by repressors are less consistent than those controlled by activators. Is this because the gross expression level of these factors tends to be lower in repressor controlled networks?
3. the function of microRNA's in the cell
4. I think the prospect of patching together the various subsections of regulatory networks will be an intriguing challenge for future researchers. Many parts of the whole have been resolved, but incorporating all of these together to form the entire network seems daunting considering the highly diverse methods that have been used to determine their dynamics.
James Pino
ReplyDeleteAsng_25A
0: Knew: Spatiotemporal range of events of an organism.
1:Learned: 40-60% of genes are subject to alternative-splicing events. There goes use of sequencing... Average of 2.5 mods per proteins. Basically a lot of facts on stats.
2: Pressing: Does connecting the genome to proteome seem too distant? Does a GFP, which is quite large, cause interactions that are not relevant?
3:Presentation: How to go from correlation, cause and effect, to kinetic, to stoichiometric levels of reconstruction.
4:Thoughts: I like how they present the paper in a "growing" fashion. It paints a clear picture of how complex things are and the difficulties in trying to reconstruct.
4: Additional thought: They use the term dynamic networks when they should be using network dynamics.
DeleteKate Jones
ReplyDeleteAssignment 25A Article 21
0. Knew: Cell signaling networks provide the framework for developing mathematical models. Alternative splicing leads to splice variants forming different proteins from the same gene.
1. Learned:I knew that alternative splicing and post-transcriptional modifications allowed for variations of proteins, but I did not know just how much variation occurred in one gene. Limits to cell signaling such as the number of receptors on a cell and how this limit changes based on cell type, limit to production and secretion rate and therefore signal speed
2. Pressing ?: Is the protein level the only limiting factor that makes identifying PTMs difficult? Is there a way to increase the number of receptors or production rate of a cell?
3. Presentation: Impact of a small number of proteins interacting in a combinatorial way; adding one interaction and how that expands the network
4. Thoughts: This knowledge makes building interaction maps more difficult because maybe only specific forms of a protein interact in the expected way while other forms do something different. I liked the definitions in the margins of some of the key words.
Arman Chowdhury
ReplyDeleteAssignment 25A
0. Knew: Vaguely about cellular biochemical network reconstruction
1. Learned: I found these 5 questions (that should be asked for signalling network reconstruction) to be useful to understand the whole paper: 1) What proteins and other network components participate? 2) What are the ligand–receptor interactions? 3) What are the receptor–intracellular-component
interactions? 4) What are the intracellular-component–intracellularcomponent
interactions? 5) What are the intracellular-component–DNA interactions?
2. Pressing?:
3. Presentation: Different types and number of cellular components, and order of magnitudes for timescales in signalling networks are well quantified in tables.
4 Thoughts: This article seems to set up a good premise for building a network reconstruction. It talks about the different aspects to consider and cautions against oversimplification. But, I wish the text was a bit more organized.