Systems Biology Commons^™

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 ...

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 ...

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 ...

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 ...

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 ...

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 ...

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.

Evolved Bacterial Resistance Against Fluoropyrimidines Can Lower Chemotherapy Impact In The Caenorhabditis Elegans Host, Brittany Rosener, Serkan Sayin, Peter O. Oluoch, Aurian Garcia-Gonzalez, Hirotada Mori, Albertha J. M. Walhout, Amir Mitchell

Open Access Publications by UMMS Authors

Metabolism of host-targeted drugs by the microbiome can substantially impact host treatment success. However, since many host-targeted drugs inadvertently hamper microbiome growth, repeated drug administration can lead to microbiome evolutionary adaptation. We tested if evolved bacterial resistance against host-targeted drugs alters their drug metabolism and impacts host treatment success. We used a model system of Caenorhabditis elegans, its bacterial diet, and two fluoropyrimidine chemotherapies. Genetic screens revealed that most of loss-of-function resistance mutations in Escherichia coli also reduced drug toxicity in the host. We found that resistance rapidly emerged in E. coli under natural selection and converged to a handful ...

Dormancy-To-Death Transition In Yeast Spores Occurs Due To Gradual Loss Of Gene-Expressing Ability, Theo Maire, Tim Allertz, Max A. Betjes, Hyun Youk

Open Access Publications by UMMS Authors

Dormancy is colloquially considered as extending lifespan by being still. Starved yeasts form dormant spores that wake-up (germinate) when nutrients reappear but cannot germinate (die) after some time. What sets their lifespans and how they age are open questions because what processes occur-and by how much-within each dormant spore remains unclear. With single-cell-level measurements, we discovered how dormant yeast spores age and die: spores have a quantifiable gene-expressing ability during dormancy that decreases over days to months until it vanishes, causing death. Specifically, each spore has a different probability of germinating that decreases because its ability to-without nutrients-express genes decreases ...

Estimating The Number Of Discrete Models Of Biological Networks, Brandilyn Stigler

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Mathematical Modelling And In Silico Experimentation To Estimate The Quantity Of Covid-19 Infected Individuals In Tijuana, México, Karla A. Encinas, Luis N. Coria, Paul A. Valle

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Transparent Soil Microcosms For Live-Cell Imaging And Non-Destructive Stable Isotope Probing Of Soil Microorganisms, Kriti Sharma, Marton Palatinszky, Georgi Nikolov, David Berry, Elizabeth A. Shank

Open Access Publications by UMMS Authors

Microscale processes are critically important to soil ecology and biogeochemistry yet are difficult to study due to soil's opacity and complexity. To advance the study of soil processes, we constructed transparent soil microcosms that enable the visualization of microbes via fluorescence microscopy and the non-destructive measurement of microbial activity and carbon uptake in situ via Raman microspectroscopy. We assessed the polymer Nafion and the crystal cryolite as optically transparent soil substrates. We demonstrated that both substrates enable the growth, maintenance, and visualization of microbial cells in three dimensions over time, and are compatible with stable isotope probing using Raman ...

Clustering Of Strong Replicators Associated With Active Promoters Is Sufficient To Establish An Early-Replicating Domain, Caroline Brossas, Anne-Laure Valton, Sergey V. Venev, Sabarinadh Chilaka, Antonin Counillon, Marc Laurent, Coralie Goncalves, Benedicte Duriez, Franck Picard, Job Dekker, Marie-Noelle Prioleau

Open Access Publications by UMMS Authors

Vertebrate genomes replicate according to a precise temporal program strongly correlated with their organization into A/B compartments. Until now, the molecular mechanisms underlying the establishment of early-replicating domains remain largely unknown. We defined two minimal cis-element modules containing a strong replication origin and chromatin modifier binding sites capable of shifting a targeted mid-late-replicating region for earlier replication. The two origins overlap with a constitutive or a silent tissue-specific promoter. When inserted side-by-side, these modules advance replication timing over a 250 kb region through the cooperation with one endogenous origin located 30 kb away. Moreover, when inserted at two chromosomal ...

Chromosome-Level Assembly Of The Atlantic Silverside Genome Reveals Extreme Levels Of Sequence Diversity And Structural Genetic Variation [Preprint], Anna Tigano, Arne Jacobs, Aryn P. Wilder, Ankita Nand, Ye Zhan, Job Dekker

University of Massachusetts Medical School Faculty Publications

The levels and distribution of standing genetic variation in a genome can provide a wealth of insights about the adaptive potential, demographic history, and genome structure of a population or species. As structural variants are increasingly associated with traits important for adaptation and speciation, investigating both sequence and structural variation is essential for wholly tapping this potential. Using a combination of shotgun sequencing, 10X Genomics linked reads and proximity-ligation data (Chicago and Hi-C), we produced and annotated a chromosome-level genome assembly for the Atlantic silverside (Menidia menidia) - an established ecological model for studying the phenotypic effects of natural and artificial ...

Modeling Tissue-Relevant Caenorhabditis Elegans Metabolism At Network, Pathway, Reaction, And Metabolite Levels, L. Safak Yilmaz, Xuhang Li, Shivani Nanda, Bennett Fox, Frank Schroeder, Albertha J. M. Walhout

Open Access Publications by UMMS Authors

Metabolism is a highly compartmentalized process that provides building blocks for biomass generation during development, homeostasis, and wound healing, and energy to support cellular and organismal processes. In metazoans, different cells and tissues specialize in different aspects of metabolism. However, studying the compartmentalization of metabolism in different cell types in a whole animal and for a particular stage of life is difficult. Here, we present MEtabolic models Reconciled with Gene Expression (MERGE), a computational pipeline that we used to predict tissue-relevant metabolic function at the network, pathway, reaction, and metabolite levels based on single-cell RNA-sequencing (scRNA-seq) data from the nematode ...

Caenorhabditis Elegans Methionine/S-Adenosylmethionine Cycle Activity Is Sensed And Adjusted By A Nuclear Hormone Receptor, Gabrielle E. Giese, Melissa D. Walker, Olga Ponomarova, Hefei Zhang, Xuhang Li, Gregory Minevich, Albertha J. M. Walhout

Open Access Publications by UMMS Authors

Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and the methionine/S-adenosylmethionine (Met/SAM) cycle. In Caenorhabditis elegans, low vitamin B12, or genetic perturbation of the canonical propionate breakdown pathway results in propionate accumulation and the transcriptional activation of a propionate shunt pathway. This propionate-dependent mechanism requires nhr-10 and is referred to as 'B12-mechanism-I'. Here, we report that vitamin B12 represses the expression of Met/SAM cycle genes by a propionate-independent mechanism we refer to as 'B12-mechanism-II'. This mechanism is activated by perturbations in the Met/SAM cycle, genetically or due ...

Large Domains Of Heterochromatin Direct The Formation Of Short Mitotic Chromosome Loops, Maximilian H. Fitz-James, Pin Tong, Alison L. Pidoux, Hakan Ozadam, Liyan Yang, Sharon A. White, Job Dekker, Robin C. Allshire

Open Access Publications by UMMS Authors

During mitosis chromosomes reorganise into highly compact, rod-shaped forms, thought to consist of consecutive chromatin loops around a central protein scaffold. Condensin complexes are involved in chromatin compaction, but the contribution of other chromatin proteins, DNA sequence and histone modifications is less understood. A large region of fission yeast DNA inserted into a mouse chromosome was previously observed to adopt a mitotic organisation distinct from that of surrounding mouse DNA. Here, we show that a similar distinct structure is common to a large subset of insertion events in both mouse and human cells and is coincident with the presence of ...