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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 […]

Featurizing Multi-Sample CyTOF Datasets to Predict Clinical and Experimental Phenotypes

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

This talk introduces fully automated featurization or summarization approaches for encoding properties of diverse immune cell-types and their functional states assayed through single-cell immune profiling techniques, such as CyTOF. The algorithms introduced enable compact summarization of each sample profiled in a multi-sample single-cell datasets, such as these representations can be used to predict clinical or […]

Genotype-to-phenotype Mapping with Artificial Intelligence

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

In this talk, I will outline challenges and opportunities associated with learning genotype -> phenotype maps using methods from artificial intelligence. In addition to describing a number of case studies from tumor progression and adverse vaccine reactions to antiviral remittances and gene expression profiling, I will outline a research program that integrates wet-lab and dry-lab […]

Engineering Strategies to Model and Treat Neurodegeneration

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

Our lab is generally focused on modeling, understanding, and treating neurodegenerative disease by integrating concepts across engineering, neuroscience, and cellular and molecular biology. We regularly leverage simple cell culture platforms, 3D engineered systems, human tissue, and in vivo models to study biological function and deconstruct mechanisms of disease. We also seek to develop engineered platforms, […]

Machine Learning for Drug Discovery: From Large Molecule Drug Discovery to Cross Modality Frameworks

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

We will discuss the development of new machine learning methods for drug discovery. We will initially focus on an iterative, and active learning powered, approach to optimizing existing large molecule (antibody) leads. We will compare multiple new methods for generating antibody like sequences, and evaluate their utility in a multi-drug-property optimization setting. We will also […]

Time-Resolved Dynamics of Human Brain Activity

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

Functional magnetic resonance imaging (fMRI) provides a valuable window into the human brain. Spontaneous fluctuations in fMRI signals are found to form highly structured patterns across the brain, revealing the organization of large-scale functional networks. Further, a growing body of work indicates that the temporal dynamics of these signals carry information about internal states such as alertness and […]

Seeing With New Eyes: Alveologenesis in 4D

Light Hall 412

Jennifer Sucre, M.D. Assistant Professor of Pediatrics Assistant Professor of Cell & Developmental Biology Mildred Stahlman Division of Neonatology Monroe Carell, Jr. Children's Hospital Vanderbilt University, School of Medicine Hybrid Available - https://vanderbilt.zoom.us/j/93829011951 Passcode - 370515 Student and trainee lunch to immediately follow. Please email rebecca.l.sykes@vanderbilt.edu with any questions.

Systems Insights into Quantitative Variability and Divergent Cancer Phenotypes

Bass Conference Room - RRB 436

One of the major challenges of systems biology is to understand how heterogeneity arises in cells in uniform environment. Biological systems are highly heterogeneous, however, not all differences in cells result in distinct qualitative phenotypes. In this talk, I will present my work that utilizes a cancer systems biology approach in identifying the molecular variability […]

Hidden in the Canopy: Unveiling Physical and Biochemical Innovations for Camouflage and Transparency in Neotropical Leaf-Dwelling Frogs

Bass Conference Room - RRB 436

Hundreds of neotropical frogs evolved biochemical tricks for signaling and camouflage involving strong fluorescence, novel colored proteins, and remarkable cardiovascular mechanisms that maintain the transparency of their tissues. In particular, green treefrogs co-opted a group of serpin proteins –with ancient immunological and blood coagulation functions– that bind biliverdin and make the animals leaf-like green, matching […]

Modeling Cell Signaling From Molecules to Macrostructures

Bass Conference Room - RRB 436

Cells use receptors on their surface to detect signals, such as hormones or growth factors, in their environment. These receptors then activate signaling pathways that transmit this information to the cellular machinery required to mount an appropriate response. Often this involves a change in cell shape or directed movement, and therefore requires regulation of the […]