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Early life microbiota development and childhood asthma – microbes to mechanisms

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A presentation by Susan Lynch Professor of Medicine, Director, Benioff Center for Microbiome Medicine, University of California: San Francisco Zoom link https://us02web.zoom.us/j/87550168229 The prevalence of allergy and asthma has increased significantly over the past several decades, but particularly so in industrialized nations where environmental exposures and lifestyles have rapidly diverged from those with which humans […]

Using Single-Cell Multiplexed Imaging and Manifold Learning to Visualize Cell Cycle Plasticity in Health and Disease

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A Presentation by Wayne Michael Stallaert, Ph.D. Postdoctoral Researcher in Computational Medicine, University of North Carolina at Chapel Hill The recent development of single-cell approaches to study the cell cycle (e.g. time-lapse imaging of fluorescent cell cycle biosensors) has revealed that cells do not always take the same molecular path through the cell cycle. This […]

Precision and Plasticity in Animal Transcription

Over the past decade, our group has focused on discerning the molecular mechanisms that can reconcile how transcriptional control during animal development can be simultaneously precise (e.g. sharp in response to variable inputs) and plastic (e.g. able to harbor genetic variation at multiple scales). I will discuss how our work supports a view of transcription […]

A Model of Non-modular Biochemical Oscillator and Switch

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Negative and positive feedback loops have been considered essential components for biological rhythms and switches, respectively. Research in systems biology focused on gene regulatory networks with intuitive appearances of feedback loops, leaving unknown whether other common biochemical reactions can produce oscillatory or switch-like dynamics. We used mass-action-based models to show that regulated RNA degradation involving […]

Highly-multiplexed tissue imaging at the Laboratory of Systems Pharmacology and beyond

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Single-cell technologies have revolutionized our ability to characterize biological systems. An exciting direction for quantitative biology is the recent emergence of spatial -omics technologies, which promise to spatially resolve single-cell measurements and allow us to study cell neighborhoods in unprecedented detail. In this talk, I will provide an overview of highly-multiplexed tissue imaging, a particular class of methods that uses fluorescence […]

From Data to Knowledge in Network-Driven Cellular Processes

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A mechanistic understanding of cellular processes continues to be an elusive goal of quantitative biology. Measurements across multiple spatiotemporal resolutions are routinely collected but how these data impact our understanding of biological processes is often not clear. In this presentation, I will address the link between data and knowledge across multiple data types and explore […]

Modeling intra-cellular insulin dynamics in pancreatic Beta cells

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In this talk, I will discuss the role of cytoskeletal processes in regulating insulin dynamics in pancreatic cells. Due to the increasing prevalence of diabetes and related disorders, understanding how individual cells regulate insulin availability and secretion in response to glucose stimulation is of utmost importance. I will focus on the intra-cellular (rather than systemic) […]

Redundancy and fragility in a young but essential gene regulatory network

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Early in embryogenesis, C. elegans worms use a short network of interacting and related transcription factors to establish gut cell identity. The goal is to activate a downstream master regulator which stays on throughout a worm's life and directs gut differentiation and maintenance. Although the network is robust to deletions of some of its trans-activators, […]

Systems Biology Insights into Antimicrobial Resistance Physiology

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Bactericidal antibiotics are conventionally understood to kill bacteria through a target-dependent process mediated by antibiotic inhibition of replicative machinery. However, several lines of evidence suggest that other aspects of bacterial physiology may also play a decisive, causal role. Yet, the interplay between bacterial metabolism and bactericidal antibiotic lethality is challenging to study due to the […]

Demystifying Scientific Publishing from the Perspective of a Researcher Turned Editor

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Papers are the core currency of scientific research; not only are they the primary medium researchers use to communicate their work, but the number of papers a researcher publishes and where they are published is often used as a proxy for a researcher’s worthiness of grants and promotion. Today, commercial publication is handled by five […]

Expanding the Genomechanics Toolbox: New Techniques to Investigate Metastatic Mechanical and Genetic Data at Single Cell Level across the Genome

Engineering & Science Building 048 Vanderbilt University, Nashville

Nine out of every ten cancer-related deaths is caused by metastasis, but the molecular mechanisms driving this process are still not fully understood. Several studies have implicated that as a cell’s metastatic potential increases, cell stiffness decreases. Yet while certain genes that affect cell mechanics have been studied, a genome-wide study of networks that modulate […]

Building the Cell from Unreliable Parts: the Case of Stochastic Organelle Biogenesis

Engineering & Science Building 048 Vanderbilt University, Nashville

Perhaps the defining feature of the eukaryotic cell is its organization into membrane-bound compartments known as organelles. While the processes underlying the biogenesis of individual organelles are often well-known the precision with which individual cells exert quantitative control over individual organelle properties, such as number and size, and coordinate these properties at systems-scale across the […]

Interpretable Deep Learning for Cancer Personalized Medicine

Engineering & Science Building 048 Vanderbilt University, Nashville

In recent years, deep learning models have resulted in outstanding breakthrough performances. However, many models behave as black boxes that can hide data biases, incorrect hypotheses or even software errors. In this talk, I will illustrate how interpretable deep learning models can achieve both high prediction accuracy and transparency. First, I will introduce multi-modal deep […]

Modeling Transcriptional Dynamics from Single-Cell Genomics Data

Engineering & Science Building 048 Vanderbilt University, Nashville

Single-cell genomics technologies have been lauded for their potential to probe biological systems with cell type specificity, and to elucidate cellular differentiation trajectories. However, the analysis of single-cell genomics data is fraught with numerous computational challenges. I will show that biophysical models of transcriptional dynamics are helpful in resolving some of these challenges and outline […]

A Computational Model of Crosstalk Between MAPK Signaling and Store-Operated Calcium Entry in Melanoma Cells

Engineering & Science Building 048 Vanderbilt University, Nashville

BRAF-mutant melanoma cells under prolonged BRAF inhibition have been shown to enter a state of balanced division and death, termed "idling."It is hypothesized that the idling state acts as a haven into which cancer cells can escape to survive drug treatments and that idling cells eventually acquire genetic resistance mutations, driving tumor recurrence. There may […]

Exploring Bacterial Phenotypic Heterogeneity with Single-Cell Transcriptomics

Engineering & Science Building 048 Vanderbilt University, Nashville

Even isogenic bacteria may heterogeneously express different subsets of genes, assuming distinct roles for the survival of the community. There is limited knowledge about the diversity of phenotypic states within complex bacterial communities which are ill-suited for reporter-based approaches. Overcoming technical challenges associated with bringing the technology used for eukaryotic cells to prokaryotes, we developed […]

Model-Driven Design of Optical Microscopy Experiments to Harvest Single-Cell Fluctuation Information while Rejecting Image Distortion Effects

Engineering & Science Building 048 Vanderbilt University, Nashville

Modern fluorescence labeling and optical microscopy approaches make it possible to observe every stage of basic gene regulatory processes, even at the level of individual DNA, RNA, and protein molecules, in living cells, and within fluctuating environments. To complement these observations, the mechanisms and parameters of discrete stochastic models can be rigorously inferred to reproduce […]

Combining Experiments with Computational Models to Engineer Tissue

Engineering & Science Building 048 Vanderbilt University, Nashville

The most prevalent, devastating, and complex diseases of our time, such as diabetes, cardiovascular disease, cancer, and infectious diseases, involve the dynamic interactions of cells with one another and with their changing environment. However, the drugs we typically use to treat diseases target a single protein and disregard the fact that cells within tissues are […]

Logarithmic Signaling Regulates MAPK Stress Response and Survival

Bass Conference Room - PRB 436

Signaling mechanisms enable cells to sense, respond, and adapt to changing environments. Understanding signal transduction mechanisms at both molecular and network levels is critical to characterize key proteins and reaction rates in the cellular response in normal and pathophysiological conditions. This insight is important to discover unknown regulatory mechanisms, to identify abnormal protein interactions, and […]

Investigating Lung Diseases and the Use of Causal Modeling in Multi-Scale Medical Research

Light Hall 415ABCD

The advancement of technologies for high-throughput collection of molecular and clinical data, has inadvertently transformed biology and medicine.  Integrating and co-analyzing these different data streams has become the research bottleneck and, in all likelihood, will be a central research topic for the next decade.  My group has historically worked on the development of statistical and […]