Suddath Award Winner Presentation

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"Investigation of altered signaling pathways in aging T cells using microfluidic platforms and computational modeling"

Catherine-Aurel Rivet - Co-Advisors, Melissa Kemp, PhD, and Hang Lu, PhD

For many years, it was believed that reactive oxygen species (ROS) were only detrimental, causing damage to DNA and proteins; however, it has become clear that ROS, particularly H2O2, can act as intracellular signaling molecules that link cellular redox state to such processes as cell proliferation and differentiation. There are common features between regulation by H2O2 and other second messengers such as calcium; calcium ions also participate in the control of cell differentiation, gene transcription and effector functions. Recent experimental evidence indicates that these mechanisms are not independent. Calcium signaling in T lymphocytes can be fine-tuned by intracellular ROS levels at different steps of the calcium release pathway, and ROS production is tightly regulated by intracellular calcium levels. Local contacts between mitochondria and ER are one possible mechanism used by cells to maintain homeostasis of their signaling molecules. Control of intracellular calcium and ROS is essential for cell survival and function and disruptions of either signaling molecules regulation lead to a range of pathological conditions. Immunosenescence, which corresponds to the dysregulation of the immune system occurring with aging, is a condition where calcium signaling and ROS levels are perturbed; however, whether impaired calcium signaling is a result of the oxidative shift is still unknown. Because testing experimentally cross-talks between the calcium and ROS signaling pathways at the molecular level is technically challenging, I propose to combine microfluidics-based assays and mathematical modeling as an integrative approach to understand and analyze the dynamical behavior of this system. These mathematical models will serve as a basis to investigate specific age related modifications in an in vitro model of cell aging. The high-throughput, semi-automated microfluidic platforms designed in this study will enable controlled cell stimulation and spatially-resolved tracking at the single cell level. The rationale of this project is that understanding how redox levels alter calcium channel function will provide leads for the design of therapeutic interventions that target oxidative stress response at the organelle level.

Ms. Rivet's talk will be given in the IBB Suddath Seminar room, 1128, to be followed by community-wide poster session and reception in IBB's atrium. Please email us if your lab will present a poster. 


  • Workflow Status: Published
  • Created By: Colly Mitchell
  • Created: 01/17/2012
  • Modified By: Fletcher Moore
  • Modified: 10/07/2016

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