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Department of Computational and Systems Biology Seminar: Dr Elizabeth Proctor

When:
May 2, 2017 @ 3:00 pm – 4:00 pm
2017-05-02T15:00:00-04:00
2017-05-02T16:00:00-04:00
Where:
6014 BST3

Title: Atoms to Systems: A Multi-Scale Approach to Modeling and Correcting Disease Pathology

Abstract:
Pathological phenomena at scales from the molecular to the organismal level converge to result in disease, but most studies focus on a single phenomenon in isolation from those occurring in parallel or on different scales. The tools of systems biology can be used to unite these phenomena into a holistic picture of biological function in order to better understand and correct pathology and engineer biological systems, especially in complex diseases such as neurodegeneration and diabetes. In neurodegenerative diseases, protein misfolding and aggregation has been implicated in pathology, but the specific toxic mechanisms of disease progression initiated by these species remain unknown and uncharacterized. Inflammation is also thought to play a major role in disease onset and progression, but the mechanism linking the two phenomena is still unclear. To explore the mechanisms of neurotoxicity instigated by misfolded protein oligomers, we developed a multi-scale approach to characterize dysregulated inter- and intra-cellular signaling pathways in human tissue and a cellular culture system. We then leveraged our knowledge of differences between the disease and healthy systems to correct the aberrant molecular signaling reaction of cells to misfolded protein species and rescue neuron viability. In the related condition of type 2 diabetes, both metabolic and immune dysfunction are well-established trademarks of disease, but the relation and interplay of pathology in these two systems of the body is under-explored. To understand the link between metabolic changes and inflammation in type 2 diabetes, we monitored metabolic pathways and inflammatory signaling in ex vivo cellular systems under different accessible fuel regimes. We uncovered flaws in immune cell metabolism in type 2 diabetes that result in production of a known inflammatory signature of disease. Elucidation of mechanisms that link disease processes across scales and systems of the body provides greater context for pathological processes, offering promise for design of effective therapeutic strategies for complex diseases.

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