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Modeling intra-cellular insulin dynamics in pancreatic Beta cells

Zoom

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, United States

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, United States

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, United States

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, United States

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, United States

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, United States

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, United States

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, United States

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 - RRB 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 […]

The Evolution of Immune System Architecture and Deployment

Bass Conference Room - RRB 436

Many pathways involved in innate immunity in plants, insects, and mammals also play roles in host development. This genetic pleiotropy could constrain the ability of immune systems to rapidly evolve in response to selective pressure from microbes because adaptive evolution could negatively affect other developmental processes and thus host fitness. Does pleiotropy constrain adaptive evolution, […]

Applications of Quantitative Systems Biology and Machine Learning

Bass Conference Room - RRB 436

Biotechnology is rapidly improving, largely due to our ability to manipulate genetic material and efficiently measure biological processes. This talk will describe advances in computational approaches and experimental platforms to probe and control stochastic biological processes within individual cells under a microscope. First, I will describe a novel platform for interfacing individual cells with computational models of […]

Modeling Subcellular Mass Distributions with Optimal Transport: Applications in Cancer

Bass Conference Room - RRB 436

Microscopic imaging techniques have given us access to high fidelity measurements of subcellular molecule and protein mass distributions. Quantitative analysis of these has the potential to elucidate biological mechanisms as well help perform diagnosis and clinical outcome predictions in cancer and other pathologies. By using the mathematics of optimal transport we can quantitatively compare distributions […]

More than genetics: the role of the ecosystem in cancer evolution and treatment resistance

Light Hall 415ABCD

Somatic evolution is increasingly being recognized as the main driver not only in cancer progression but importantly in the emergence of resistance to existing treatments. Much of the focus in the research of evolution in cancer has been devoted to leveraging existing -omics tools to evaluate how tumors change but Darwinian evolution requires us to […]

Using agent-based modeling as “virtual laboratory”

RRB 736

Agent-based models simulate individual cells as software objects, each with their own independent states and behavioral “rules” that codify our biological hypotheses. Generally, they also are tied to models of the chemical microenvironment to emulate the motion of oxygen, growth and signaling factors, and therapeutic compounds. Together, these can form a “virtual laboratory” to computational […]

Transcriptional stochasticity reveals multiple mechanisms of long non-coding RNA regulation at the Xist-Tsix locus

Engineering & Science Building 048 Vanderbilt University, Nashville, United States

Long noncoding RNAs (LncRNAs) are increasingly recognized as being involved in human physiology and diseases, but there is a lack of mechanistic understanding for the majority of lncRNAs. We comparatively tested proposed mechanisms of antisense lncRNA regulation at the X-chromosome Inactivation (XCI) locus. Our single-cell analyses argue against mechanisms that require the Xist or Tsix […]