The complex life of MTOR

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    The serine/threonine kinase mechanistic target of rapamycin (MTOR) translates environmental cues to intracellular decisions. In response to changes in nutrient and growth factor availability, MTOR regulates virtually all metabolic processes to promote cell growth, proliferation and survival. Not surprisingly, dysregulation of MTOR signaling is a common feature in a variety of pathologies, such as neurodevelopmental disorders and cancer.
    MTOR exists in two structurally and functionally distinct complexes, namely mTOR complex 1 (mTORC1) and mTORC2. The mTOR complexes are at the center of a network that exhibits a high degree of complexity due to extrinsic and intrinsic inputs and outputs, several feedback and feedforward mechanisms and multi-level crosstalk with other kinase networks. Hence, predicting responses of this network to perturbations by metabolic signals or drugs is not intuitively possible. The MTOR interactome suggests that the network is even bigger than currently appreciated and we are only beginning to understand its real complexity.
    Systems modeling emerges as a valuable tool to dissect this complexity and may offer the potential to simulate altered mTOR signaling also for individualized medicine. However, computational models are limited by the accuracy of the data used for their parametrization.
    In my PhD thesis, I provide novel insights into the complexity of the MTOR signaling network by offering a new methodology for higher accuracy measurements and by discovering new network members inside and outside the known MTOR complexes.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Thedieck, Kathrin, Supervisor
    • Nothwang, H. G. , Supervisor, External person
    • Brandstetter, Thomas, Co-supervisor, External person
    Award date22-Dec-2020
    Place of Publication[Groningen]
    Publisher
    DOIs
    Publication statusPublished - 2020

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