Saturday, March 28, 2015

SysBio15 Asgn_24B_Class_24_Article_20_2015_04_02

EGFR signaling: Scan Article 20  K. Oda, Y. Matsuoka, A. Funahashi, and H. Kitano. A comprehensive pathway map of epidermal growth factor receptor signaling. Mol.Sys.Biol. 1:Article 2005.0010, 2005. Do NOT get lost in the details!! Post a PCRC.

3 comments:

  1. Arman Chowdhury
    Assignment 24 B

    0. Knew: Bow-tie structure of EGFR signaling is supposed to represent a versatile and conserved group of molecules and interactions.

    1. Learned: The EGFR signaling network has two positive and six negative feedback loops, and inhibitory feed forward paths. ErBb pathway dynamics is also affected by positive and negative feedback loops from the GPCR cascade.

    2. Pressing?: Has any research team yet attempt to use this map to create a comprehensive mathematical model of the entire map (using differential equations to show rate of change, for example)?

    3. Presentation: The paper seems a bit disjointed at times and does not seem to follow a strict organization, since it is neither an experimental research article nor a review article. However, the researchers did a good job explaining how to use the maps and presenting their conclusions.

    4. Thoughts: EGFR pathway maps look impressive. They have done a good job explaining construction methodology, notations, and limitations of the maps. CellDesigner seems like a good modelling tool, and potentially resourceful to other scientists and engineers. The comprehensive bibliography can also be used as a great research tool.

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  2. Cameron Togrye
    Assignment 24B

    0. Knew: EGF and its related proteins have a bow tie shape for their signalling pathways. There is a number of input signal molecules with redundancy, yet specificity for the variosu ERB receptors. These signaling cascades eventually reach a set of core pathways. These signals are eventually spread through various cascades to specific outputs.

    1. Learned: I was unaware that GPCR pathways could transactivate the EGF pathway through IP3 and calcium influxes. I was also surprised to read that some ERBB dimers were as the paper stated "not biologically meaningful". (Is this too rash of a judgment?)

    2. Pressing: In the paper it mentions (page 3) that because of the redundancy of ligand binding, the dysfunction of one receptor could be compensated for by other receptors that share some affinity to the ligand which once bound to the dysfunctional receptor? Is this a typo? Isn't it the activation of the receptor which causes the desired signal cascade? Didn't last class' paper show that deletion of some of these receptors was fatal?

    3. Examples of inhibitory feed forward pathways

    4. What are the advantages of this paper over the one from last class? It is the methodology it developed for characterizing the pathways? Also, why did the paper give us the full pathway as a figure first, before teaching us the diagram conventions?

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  3. Tim Lee
    Asgn_24B

    0. Knew: Structure of ERBB network is a bow-tie. Core process of processing many inputs to create many outputs through simple feedback loops and dimerization and phosphorylation combinations.

    1. Learned: Specific number of feedback loops identified. There is an immense amount of protein interaction that was modeled through the software CellDesigner. There are still some ambiguous protein interactions found upon the making of the map.

    2. Pressing: Can the map display outputs based on spatio-temporal regulation of protein interactions?

    3. Presentation: Description of ERBB network through mapping.

    4. Thoughts: The map is huge.

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