Savas Tay Lab

Savas Tay

Institute for Genomics & Systems Biology

The University of Chicago

Knapp Center for Biomedical Discovery

900 East 57th Street

10th floor

Chicago, IL 60637

Phone: 773-702-6685

About the Lab

Tay Lab for Bioengineering and Systems Biology

We want to understand how cells process information, especially in the context of the immune response. NF-kappaB is a central innate immune pathway that responds to hundreds of signals including cytokines and pathogens, and controls the expression of thousands of genes. We previously investigated NF-kappaB dynamics at the single-cell level using high-throughput microfluidic microscopy and quantitative gene expression (Tay et al. Nature 466, 267). Contrary to what bulk assays show, we discovered that single-cell responses are highly heterogeneous, both in cell activation probability and dynamics of the NF-kappaB transcription factor, as well as downstream gene expression dynamics. The input signal intensity (i.e. cytokine concentration) determines the probability of activation, response time and the duration of NF-kappaB oscillations, but not the intensity of the response (i.e. nuclear translocation amplitude), therefore termed digital activation. We also showed that digital signaling propagates to downstream target genes, with early genes activating digitally and late genes activating in analog, concentration dependent fashion.

To understand the underlying mechanisms and to predict complex signaling scenarios, we developed a stochastic computer model of the NF-kappaB pathway based on our comprehensive single-cell data. This is the most broadly applicable and accurate model of the NF-kappaB pathway to date, reproducing great majority of the observed characteristics under all input signal levels. We are using this model as a test-bed for future experiments and discoveries.

Future directions in our lab include the investigation of the mechanisms behind stochastic and digital activation, and the emergent properties of this complex signaling scheme in pathogen-host interactions and tissue inflammation. For this effort, we combined probably the most powerful arsenal of single-cell analytical tools in the world, namely high-throughput automated microfluidic cell culture, automated live cell imaging and tracking, high-throughput single-cell gene expression (qPCR) and digital-PCR, and single-cell digital protein counting. This pipeline, applied to cells expressing fluorescent fusion proteins and reporters, can generate terabytes of dynamic single-cell data every week, with unprecedented degree of control, accuracy and reproducibility. Using these awesome tools, we are investigating the spatio-temporal emergent properties of digital cell activation. New technologies based on microfluidics and optogenetics will also be developed to simulate these scenarios. Our previous single-cell model will be expanded and used to guide further experimental studies.

Lab Members

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D
Nir Drayman

Nir Drayman

Postdoc,
Savas Tay Lab
Post-Doc
G
Navid Ghorashian

Navid Ghorashian

Postdoc,
Postdoc
Savas Lab
J
Christian Jordi

Christian Jordi

PhD Student,
PhD Student
Savas Lab
Michael Junkin

Michael Junkin

Staff Scientist,
Savas Tay Lab
Senior Scientist at the Institute for Molecular Engineering
L
Jing Lin

Jing Lin

PhD Student,
Tay Lab
3128045877
Jing Lin

Jing Lin

PhD Student,
PhD Student
Savas Lab
P
Parthiv Patel

Parthiv Patel

PhD Student,
PhD Student
Savas Lab
S
Alan Selewa

Alan Selewa

PhD Student,
PhD Student
Savas Lab
(773) 834-1877
T
Savas Tay

Savas Tay

IGSB, Core Member,
Associate Professor in Molecular Engineering
773-702-4511
Hsiung-Lin Tu

Hsiung-Lin Tu

Postdoc,
Postdoc
Savas Lab
V
Hoang Van Phan

Hoang Van Phan

PhD Student,
PhD Student
Savas Lab

News

Noise Induces Hopping between NF-κB Entrainment Modes

On the cover of the December Cell Systems issue, IGSB Faculty member Savas Tay, and others, observe that when NF-κB oscillations are entrained by periodic tumor necrosis factor (TNF) inputs in experiments, NF-κB exhibits jumps between frequency modes, a phenomenon called “cellular mode-hopping.” By comparing stochastic simulations of NF-κB oscillations to deterministic simulations conducted inside and outside the chaotic regime of parameter space, they show that noise facilitates mode-hopping in all regimes. The full article can be read here.

Research Papers