Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II

85-POS Board 38 Microfluidic Single-Cell Analysis and Modeling of Cellular Information Processing Savas Tay . ETH Zurich, Basel, Switzerland. Immune cells constantly receive signaling inputs such as pathogen-emitted molecules, use gene regulatory pathways to process these signals, and generate outputs by secreting signaling molecules. Characterizing the input-output relationship of a biological system allows building models to predict how the system will operate in complex physiological scenarios. A major obstacle here is that each cell contains its own, time-dependent composition of pathway components, generating distinct, time-varying outputs for the exact same inputs. Such variability makes time-dependent single-cell analysis crucial. Single-cell dynamical analysis, however, has been a low-throughput method due to technical challenges in isolating, manipulating and measuring individual cells. I will talk about how we address these limitations by developing automated, high-throughput, microfluidic/optofluidic single-cell analysis systems with unprecedented capabilities and measurement accuracy, and how we use them in understanding immune coordination during response to infection. Our recent efforts have resulted in a new set of technologies, including microfluidic systems to measure cytokine secretion dynamics from single-cells under complex time-varying signaling inputs, a cell culture system that creates programmable diffusion-based chemical gradients, a chip to measure cell-cell communication via secreted factors, and a new method for digital quantification of proteins and nucleic acids (mRNA and DNA) in the same cell. I will also talk about new biological insight from our experimental and modeling efforts about how single-cells detect and encode dose and frequency information using the immune pathway NF-κB, and how they create dynamic cytokine outputs under inflammatory stimuli. A primary goal in this combined technology/cell biology effort is to develop a computer model of tissue-level immune response through the NF-κB pathway, with particular focus on cytokine signal propagation mechanism (e.g. diffusion vs. waves), speed, range and duration.

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