Systems Biology Commons^™

The Mayfly Newsletter, Donna Giberson

The Mayfly Newsletter

The Mayfly Newsletter is the official newsletter of the Permanent Committee of the International Conferences on Ephemeroptera.

Knowing What We Know: Leveraging Community Knowledge Through Automated Text-Mining, Justin Gardner, Jonathan Tory Toole, Hemant Kalia, Garry Spink Jr., Gordon Broderick

Advances in Clinical Medical Research and Healthcare Delivery

No abstract provided.

Mapping The Little Brain At The Heart By An Interdisciplinary Systems Biology Team., Rajanikanth Vadigepalli, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Introduction Of Native Podostemum Ceratophyllum Michx. (Podostemaceae, Hornleaf Riverweed) Into The Norwalk River, Wilton, Ct, Kelly Marie Nealon

MS in Integrated Biological Diversity

Podostemum ceratophyllum (Podostemaceae), “Hornleaf riverweed,” is a native aquatic flowering plant that occurs only attached to rocks in fast flowing water. The species occurs in much of eastern United States and Canada. Over the last several decades the species has notably declined in numbers, largely as a result of human induced factors. The ecological importance of P. ceratophyllum in rivers is well documented. This research is the first attempt to transplant the species into a river where it was not known to occur, with the goal of helping to mitigate the loss of populations. The plant was taken from two ...

Biases And Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens, Merve Dede

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Adaptation of the bacterial CRISPR-Cas9 system to mammalian cells revolutionized the field of functional genomics, enabling genome-scale genetic perturbations to study essential genes, whose loss of function results in a severe fitness defect. There are two types of essential genes in a cell. Core essential genes are absolutely required for growth and proliferation in every cell type. On the other hand, context-dependent essential genes become essential in an environmental or genetic context. The concept of context-dependent gene essentiality is particularly important in cancer, since killing cancer cells selectively without harming surrounding healthy tissue remains a major challenge. The toxicity of ...

Perivascular Adipose Tissue In Relation To Diet, Thermogenesis And Cardiovascular Health, Ginger Paquette, Caitlin Stieber, Ashely Soucy, Benjamin Tero, Lucy Liaw

Thinking Matters Symposium

Adipose tissue is a diverse and crucial component to vascular health due to its role in energy storage and heat production. The primary function of white adipose tissue (WAT) is energy storage while the function of mitochondria-rich brown adipose tissue (BAT) is heat production. Perivascular adipose tissue (PVAT), which surrounds blood vessels, contains both WAT and BAT adipocytes. Dietary calorie restriction is associated with increased lifespan with decreased adiposity. Increased prevalence of WAT-like PVAT, due to high-fat diets and obesity, leads to increased metabolic disfunction and cardiovascular-disease. We used a calorie-restriction model in C57BL6/J mice to test the hypothesis ...

Quantifying Planarian Behavior As An Introduction To Object Tracking And Signal Processing, Nicole C. Stowell, T. Goel, Vir Shetty , '22, Jocelyne Noveral, Eva-Maria S. Collins

Biology Faculty Works

Answers to mechanistic questions about biological phenomena require fluency in a variety of molecular biology techniques and physical concepts. Here, we present an interdisciplinary approach to introducing undergraduate students to an important problem in the areas of animal behavior and neuroscience—the neuronal control of animal behavior. In this lab module, students explore planarian behavior by quantitative image and data analysis with freely available software and low-cost resources. Planarians are ∼1–2-cm-long aquatic free-living flatworms famous for their regeneration abilities. They are inexpensive and easy to maintain, handle, and perturb, and their fairly large size allows for image acquisition with ...

Controlling Gene Expression Timing Through Gene Regulatory Architecture [Preprint], Md Zulfikar Ali, Robert C. Brewster

University of Massachusetts Medical School Faculty Publications

Gene networks typically involve the regulatory control of multiple genes with related function. This connectivity enables correlated control of the levels and timing of gene expression. Here we study how the timing of gene expression in networks can be encoded in the regulatory DNA of a gene. Using stochastic simulations, we examine the role of binding affinity, TF regulatory function and network size in controlling the mean first-passage time to reach a fixed fraction of steady-state expression for both an auto-regulated TF gene and a target gene. We also examine how the variability in first-passage time depends on these factors ...

A Mathematical Model Of Pancreatic Cancer Growth And Response To Treatment, Allison Cruikshank

Honors Theses, University of Nebraska-Lincoln

Pancreatic cancer is one of the leading causes of death due to cancer in the United States. Analyzing the effects of radiation is extremely valuable in determining when a patient is allowed surgical resection, which is, presently, the only potentially curative treatment for pancreatic cancer. This study examines pancreatic tumor growth and shrinkage to predict tumor response and change of resectability for pancreatic cancer patients undergoing radiation therapy. This is done using ordinary differential equations as a mathematical model. Mathematical models have increasingly been applied to various biological systems/processes to analyze the principles involved. In our project, a population ...

Toward The Discovery Of Biological Functions Associated With The Mechanosensor Mtl1p Of Saccharomyces Cerevisiae Via Integrative Multi-Omics Analysis, Nelson Martínez-Matías, Nataliya Chorna, Sahily González-Crespo, Lilliam Villanueva, Ingrid Montes-Rodríguez, Loyda M. Melendez-Aponte, Abiel Roche-Lima, Kelvin Carrasquillo-Carrión, Ednalise Santiago-Cartagena, Brian C. Rymond, Mohan Babu, Igor Stagljar, José R. Rodríguez-Medina

Biology Faculty Publications

Functional analysis of the Mtl1 protein in Saccharomyces cerevisiae has revealed that this transmembrane sensor endows yeast cells with resistance to oxidative stress through a signaling mechanism called the cell wall integrity pathway (CWI). We observed upregulation of multiple heat shock proteins (HSPs), proteins associated with the formation of stress granules, and the phosphatase subunit of trehalose 6-phosphate synthase which suggests that mtl1Δ strains undergo intrinsic activation of a non-lethal heat stress response. Furthermore, quantitative global proteomic analysis conducted on TMT-labeled proteins combined with metabolome analysis revealed that mtl1Δ strains exhibit decreased levels of metabolites of carboxylic acid metabolism, decreased ...

Biophysical Basis Of Cellular Multi-Specificity Encoded In A Model Molecular Switch [Preprint], Tina Perica, Christopher J. P. Mathy, Jiewei Xu, Gwendolyn M. Jang, Yang Zhang, Robyn Kaake, Noah Ollikainen, Hannes Braberg, Danielle L. Swaney, David G. Lambright, Mark J. S. Kelly, Nevan J. Krogan, Tanja Kortemme

University of Massachusetts Medical School Faculty Publications

Molecular switches are central to signal transduction in protein interaction networks. One switch protein can independently regulate distinct cellular processes, but the molecular mechanisms enabling this functional multi-specificity remain unclear. Here we integrate system-scale cellular and biophysical measurements to study how a paradigm switch, the small GTPase Ran/Gsp1, achieves its functional multi-specificity. We make 55 targeted point mutations to individual interactions of Ran/Gsp1 and show through quantitative, systematic genetic and physical interaction mapping that Ran/Gsp1 interface perturbations have widespread cellular consequences that cluster by biological processes but, unexpectedly, not by the targeted interactions. Instead, the cellular consequences ...

Gastrointestinal Microbiota Composition Predicts Peripheral Inflammatory State During Treatment Of Human Tuberculosis, Matthew F. Wipperman, Shakti K. Bhattarai, Charles Kyriakos Vorkas, Venkata Suhas Maringati, Ying Taur, Laurent Mathurin, Katherine Mcaulay, Stalz Charles Vilbrun, Daphie Francois, James Bean, Kathleen F. Walsh, Carl Nathan, Daniel W. Fitzgerald, Michael S. Glickman, Vanni Bucci

Open Access Publications by UMMS Authors

The composition of the gastrointestinal microbiota influences systemic immune responses, but how this affects infectious disease pathogenesis and antibiotic therapy outcome is poorly understood. This question is rarely examined in humans due to the difficulty in dissociating the immunologic effects of antibiotic-induced pathogen clearance and microbiome alteration. Here, we analyze data from two longitudinal studies of tuberculosis (TB) therapy (35 and 20 individuals) and a cross sectional study from 55 healthy controls, in which we collected fecal samples (for microbiome analysis), sputum (for determination of Mycobacterium tuberculosis (Mtb) bacterial load), and peripheral blood (for transcriptomic analysis). We decouple microbiome effects ...

Flick: An Optimized Plate Reader-Based Assay To Infer Cell Death Kinetics, Ryan Richards, Megan E. Honeywell, Michael J. Lee

Open Access Publications by UMMS Authors

Evaluating drug sensitivity is improved by directly quantifying death kinetics, rather than correlates of viability, such as metabolic activity. This is challenging, requiring time-lapse microscopy and genetically encoded labels to distinguish live and dead cells. Here, we describe fluorescence-based and lysis-dependent inference of cell death kinetics (FLICK). This method requires only a standard fluorescence plate reader, retaining the high-throughput nature and broad accessibility of common viability assays. However, FLICK specifically quantifies death, including an accurate inference of death kinetics. For complete details on the use and execution of this protocol, please refer to Richards et al. (2020).

Functional Influence Of 14-3-3 (Ywha) Proteins In Mammals, Elizabeth Barley, Santanu De

Mako: NSU Undergraduate Student Journal

The 14-3-3 (YWHA) proteins are homologous, ubiquitous, and conserved in most organisms ranging from plants to animals and play important roles in regulating key cellular events such as cell signaling, development, apoptosis, etc. These proteins consist of seven isoforms in mammals, termed under Greek alphabetization: beta (β), gamma (γ), epsilon (ε), eta (η), tau/theta (τ), sigma (σ), and zeta (ζ). Each of these isoforms can interact with a plethora of binding partners and has been shown to serve a distinct role in molecular crosstalk, biological processes, and disease susceptibility. Protein 14-3-3 isoforms are scaffolding proteins capable of forming homodimers ...

Single-Cell Rna-Seq Reveals Transcriptomic Heterogeneity Mediated By Host-Pathogen Dynamics In Lymphoblastoid Cell Lines, Elliott D. Sorelle, Joanne Dai, Emmanuela N. Bonglack, Emma M. Heckenberg, Jeffrey Y. Zhou, Stephanie N. Giamberardino, Jeffrey A. Bailey, Simon G. Gregory, Cliburn Chan, Micah A. Luftig

Open Access Publications by UMMS Authors

Lymphoblastoid cell lines (LCLs) are generated by transforming primary B cells with Epstein-Barr virus (EBV) and are used extensively as model systems in viral oncology, immunology, and human genetics research. In this study, we characterized single-cell transcriptomic profiles of five LCLs and present a simple discrete-time simulation to explore the influence of stochasticity on LCL clonal evolution. Single-cell RNA sequencing (scRNA-seq) revealed substantial phenotypic heterogeneity within and across LCLs with respect to immunoglobulin isotype; virus-modulated host pathways involved in survival, activation, and differentiation; viral replication state; and oxidative stress. This heterogeneity is likely attributable to intrinsic variance in primary B ...

Quantifying The Regulatory Role Of Individual Transcription Factors In Escherichia Coli [Preprint], Sunil Guharajan, Shivani Chhabra, Vinuselvi Parisutham, Robert C. Brewster

University of Massachusetts Medical School Faculty Publications

Transcription factors (TFs) modulate gene expression by binding to regulatory DNA sequences surrounding target genes. To isolate the fundamental regulatory interactions of E. coli TFs, we measure regulation of TFs acting on synthetic target genes that are designed to isolate the individual TF regulatory effect. This data is interpreted through a thermodynamic model that decouples the role of TF copy number and TF binding affinity from the interactions of the TF on RNA polymerase through two distinct mechanisms: (de)stabilization of the polymerase and (de)acceleration of transcription initiation. We find the contribution of each mechanism towards the observed regulation ...

Mathematical Modeling Of Lung Inflammation: Macrophage Polarization And Ventilator-Induced Lung Injury With Methods For Predicting Outcome, Sarah B. Minucci

Theses and Dissertations

Lung insults, such as respiratory infections and lung injuries, can damage the pulmonary epithelium, with the most severe cases needing mechanical ventilation for effective breathing and survival. Furthermore, despite the benefits of mechanical ventilators, prolonged or misuse of ventilators may lead to ventilation-associated/ventilation-induced lung injury (VILI). Damaged epithelial cells within the alveoli trigger a local immune response. A key immune cell is the macrophage, which can differentiate into a spectrum of phenotypes ranging from pro- to anti-inflammatory. To gain a greater understanding of the mechanisms of the immune response in the lungs and possible outcomes, we developed several mathematical ...

Circulating Exosomal Microrna Expression Patterns Distinguish Cardiac Sarcoidosis From Myocardial Ischemia., Elliott D Crouser, Mark W Julian, Sabahattin Bicer, Vikas Ghai, Taek-Kyun Kim, Lisa A Maier, May Gillespie, Nabeel Y Hamzeh, Kai Wang

Articles, Abstracts, and Reports

OBJECTIVE: Cardiac sarcoidosis is difficult to diagnose, often requiring expensive and inconvenient advanced imaging techniques. Circulating exosomes contain genetic material, such as microRNA (miRNA), that are derived from diseased tissues and may serve as potential disease-specific biomarkers. We thus sought to determine whether circulating exosome-derived miRNA expression patterns would distinguish cardiac sarcoidosis (CS) from acute myocardial infarction (AMI).

METHODS: Plasma and serum samples conforming to CS, AMI or disease-free controls were procured from the Biologic Specimen and Data Repository Information Coordinating Center repository and National Jewish Health. Next generation sequencing (NGS) was performed on exosome-derived total RNA (n = 10 for ...

Global Community Effect: Large-Scale Cooperation Yields Collective Survival Of Differentiating Embryonic Stem Cells [Preprint], Hirad Daneshpour, Pim Van Den Bersselaar, Hyun Youk

University of Massachusetts Medical School Faculty Publications

“Community effect” conventionally describes differentiation occurring only when enough cells help their local (micrometers-scale) neighbors differentiate. Although new community effects are being uncovered for myriad differentiations, macroscopic-scale community effects - fates of millions of cells all entangled across centimeters - remain elusive. We found that differentiating mouse Embryonic Stem (ES) cells that are scattered as individuals over many centimeters form one macroscopic entity via long-range communications. The macroscopic population avoids extinction only if its centimeter-scale density is above a threshold value. Single-cell-level measurements, transcriptomics, and mathematical modeling revealed that this “global community effect” occurs because differentiating ES-cell populations secrete, accumulate, and sense ...

Linker Histone H1.8 Inhibits Chromatin-Binding Of Condensins And Dna Topoisomerase Ii To Tune Chromosome Compaction And Individualization [Preprint], Pavan Choppakatla, Bastiaan Dekker, Erin E. Cutts, Alessandro Vannini, Job Dekker, Hironori Funabiki

University of Massachusetts Medical School Faculty Publications

DNA loop extrusion by condensins and decatenation by DNA topoisomerase II (topo II) drive mitotic chromosome compaction and individualization. Here, we reveal that the linker histone H1.8 regulates chromatin levels of condensins and topo II. In vitro chromatin reconstitution experiments demonstrate that H1.8 inhibits binding of condensins and topo II to nucleosome arrays. Accordingly, H1.8 depletion in Xenopus egg extracts increased condensins and topo II levels on mitotic chromatin. Chromosome morphology and Hi-C analyses suggest that H1.8 depletion makes chromosomes thinner and longer likely through shortening the average loop size and reducing DNA amount in each ...