138
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.
