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The Application of Systems Biology in Host-Pathogen Interaction

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    The yeast killer toxin K28 belongs to the A/B toxin superfamily, which expends most domains of life (virus, bacterium and plant).  Despite their various origin, the structures of A/B toxins share striking similarities: i)They usually contain an alpha subunit for killing their target cells; ii)  there are one or more beta subunits for cell entry and intracellualr trafficking(Falnes and Sandvig, 2000).  Furthermore, consistent with their structural similarities, their mode of action are highly conserved:  A/B toxins enter the target cells via endocytosis and later reversely traffick from the Golgi apparatus to the ER, then finally reach to cytosol. The beta subunit(s) usually degrades during these processes while the alpha subunit exerts its function in the cytosol (Falnes and Sandvig, 2000). Although these toxins have been studied intensively during the past serveral decades, the knowledge with regards to the toxin entry, trafficking and killing mechanisms still remain incomplete (Schmitt et al., 2006).  Genomic scale study by using a genetically tractable system, such as the budding yeast, will shed light on the complicated interactions between the A/B toxins and their target cells. 


    In this paper (Carrol et al., 2009), the authors takes advantage of the yeast deletion library (Tong et al., 2001 ) to study the killing mechanism of an AB type toxin, the yeast killer toxin K28. By comparing the Gene ontology (Ashburner et al., 2000) processes and cellular components of the mutants obtained by the screening, their results systematically enhance our understanding towards the previously elusive mechanisms with regards to the uptake and trafficking of the toxin. Additionally, their screening identifies that the yeast AP2 complex mediates the specific uptake of the K28 toxin, assigning a new function to this long-known complex. To this end, their study not only showcases the power of systems biology in advancing current molecular biology study, but also exemplifies the essence of host and pathogen interaction: by dissecting the complicated interaction between the host and pathogen, we can gain insights into the mechanism of pathogenesis as well as the function of host components of which is elusive under normal physiological conditions. 



    The Paper to be Presented:

    A yeast killer toxin screen provides insights into AB toxin entry trafficking and killing mechanisms.pdf

    Carroll SY, Stirling PC, Stimpson HE, Giesselmann E, Schmitt MJ, Drubin DG.

    Dev Cell. 2009 Oct;17(4):552-60.



    Gene Ontology tool for the unification of biology.pdf

    Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G.

    Nat Genet. 2000 May;25(1):25-9. 

    Penetration of protein toxins into cells.pdf

    Falnes PO, Sandvig K.

    Curr Opin Cell Biol. 2000 Aug;12(4):407-13. Review.

    Yeast killer toxins, lethality and protection.pdf

    Schmitt MJ, Breinig F.

    Nat Rev Microbiol. 2006 Mar;4(3):212-21. Review.

    Systematic Genetic Analysis with Ordered Arrays of Yeast Deletion Mutants.pdf

    Tong AH, Evangelista M, Parsons AB, Xu H, Bader GD, Pagé N, Robinson M, Raghibizadeh S, Hogue CW, Bussey H, Andrews B, Tyers M, Boone C.

    Science. 2001 Dec 14;294(5550):2364-8.

    modular design for the clathrin- and actin-mediated endocytosis machinery.

    Kaksonen M, Toret CP, Drubin DG.

    Cell. 2005 Oct 21;123(2):305-20.

    Do not bother with this paper if you do not have time.


    Bioinformatic Tools Used in the Main Paper:


    GO::TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes.

    Boyle EI, Weng S, Gollub J, Jin H, Botstein D, Cherry JM, Sherlock G.

    Bioinformatics. 2004 Dec 12;20(18):3710-5. Epub 2004 Aug 5.

    Osprey: a network visualization system.

    Breitkreutz BJ, Stark C, Tyers M.

    Genome Biol. 2003;4(3):R22. Epub 2003 Feb 27.



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    Viewing 2 of 2 comments: view all
    Posted 14:49, 17 Feb 2012
    Hi Tany,
    The topic is very interesting! Are you also interested in this paper: The Genetic Landscape of a Cell?
    Posted 17:35, 17 Feb 2012
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