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    Comparative metabolic modeling and analysis of human pathogens

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    Name:
    Alyaa Mohamed Dissertation.pdf
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    4.902Mb
    Format:
    PDF
    Description:
    Alyaa Mohamed Dissertation
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    Type
    Thesis
    Authors
    Abdel-Haleem, Alyaa M. cc
    Advisors
    Gojobori, Takashi cc
    Committee members
    Gao, Xin cc
    Al-Babili, Salim cc
    Bajic, Vladimir B. cc
    Lewis, Nathan
    Program
    Bioscience
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Date
    2019-08
    Embargo End Date
    2020-08-01
    Permanent link to this record
    http://hdl.handle.net/10754/656294
    
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    Access Restrictions
    At the time of archiving, the student author of this thesis opted to temporarily restrict access to it. The full text of this thesis became available to the public after the expiration of the embargo on 2020-08-01.
    Abstract
    Infectious diseases continue to be major health concerns worldwide. Although major advances have led to accumulation of genomic data about human pathogens, there clearly exists a gap between genome information and studies aiming at identifying potential drug targets. Here, constraint-based modeling (CBM) was deployed to integrate disparate data types with genome-scale metabolic models (GEMs) to advance our understanding of the pathogenesis of infectious agents with respect to identifying and prioritizing drug targets. Specifically, genome-scale metabolic modeling of multiple stages and species of Plasmodium, the causative agent of malaria, was used to prioritize potential drug targets that could be used to simultaneously treat (anti-malarials) and block transmission of the parasite. In addition, species-specific metabolic models were used to guide translation of findings from non-human experimental disease models to human-infecting species. Further, comparative analysis of the essentiality of metabolic genes for V. cholerae, the causative agent of cholera, growth and survival in single and co-infections with other enteric pathogens led to prioritizing conditionally independent essential genes that would be potential drug targets in both single and co-infection scenarios. Taken together, our findings highlight the utility of using genome-scale metabolic models to prioritize druggable targets that would be of broader spectrum against human pathogens.
    Citation
    Abdel-Haleem, A. M. (2019). Comparative metabolic modeling and analysis of human pathogens. KAUST Research Repository. https://doi.org/10.25781/KAUST-9G8OS
    DOI
    10.25781/KAUST-9G8OS
    ae974a485f413a2113503eed53cd6c53
    10.25781/KAUST-9G8OS
    Scopus Count
    Collections
    Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program; Theses

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