Systems Biology Commons^™

Advancing Human Health In The Decade Ahead: Pregnancy As A Key Window For Discovery: A Burroughs Wellcome Fund Pregnancy Think Tank., Yoel Sadovsky, Sam Mesiano, Graham J Burton, Michelle Lampl, Jeffrey C Murray, Rachel M Freathy, Anita Mahadevan-Jansen, Ashley Moffett, Nathan D Price, Paul H Wise, Derek E Wildman, Ralph Snyderman, Nigel Paneth, John Anthony Capra, Marcelo A Nobrega, Yaacov Barak, Louis J Muglia

Articles, Abstracts, and Reports

Recent revolutionary advances at the intersection of medicine, omics, data sciences, computing, epidemiology, and related technologies inspire us to ponder their impact on health. Their potential impact is particularly germane to the biology of pregnancy and perinatal medicine, where limited improvement in health outcomes for women and children has remained a global challenge. We assembled a group of experts to establish a Pregnancy Think Tank to discuss a broad spectrum of major gestational disorders and adverse pregnancy outcomes that affect maternal-infant lifelong health and should serve as targets for leveraging the many recent advances. This report reflects avenues for future …

A Phosphoinositide-Based Model Of Actin Waves In Frustrated Phagocytosis, Marco A. Avila Ponce De Leon

Biology and Medicine Through Mathematics Conference

No abstract provided.

Yeast Copper Proteins And Reactive Oxygen Species In Effecting Lifespan, Megan Bestwick

Post-Grant Reports

Mitochondria are essential organelles in most eukaryotic cells because of their role in metabolism and the production of ATP by the oxidative phosphorylation (OXPHOS) pathway, as well as other key cellular processes. Metal cofactors, such as copper (Cu) and iron (Fe), are incorporated into OXPHOS protein complexes of yeast located within the inner membrane of the mitochondria. Misincorporation or modulation of these available metals in mitochondrial enzymes leads to the production of reactive oxygen species (ROS). ROS are reactive molecules containing oxygen such as peroxides, superoxide, and hydroxyl radicals. Yeast are a good model for studying aging and the effect …

Micom: Metagenome-Scale Modeling To Infer Metabolic Interactions In The Gut Microbiota., Christian Diener, Sean M Gibbons, Osbaldo Resendis-Antonio

Articles, Abstracts, and Reports

Compositional changes in the gut microbiota have been associated with a variety of medical conditions such as obesity, Crohn's disease, and diabetes. However, connecting microbial community composition to ecosystem function remains a challenge. Here, we introduce MICOM, a customizable metabolic model of the human gut microbiome. By using a heuristic optimization approach based on L2 regularization, we were able to obtain a unique set of realistic growth rates that corresponded well with observed replication rates. We integrated adjustable dietary and taxon abundance constraints to generate personalized metabolic models for individual metagenomic samples. We applied MICOM to a balanced cohort of …

Biogeographic Variation In Resistance Of The Invasive Plant, Alliaria Petiolata, To A Powdery Mildew Fungus And Effect Of Resistance On Competitive Dynamics, Don Cipollini, Sam Davisd, Deah Lieurance, Kendra Cipollini, Volker Bahn

Biological Sciences Faculty Publications

Garlic mustard is an invasive Eurasian biennial that has spread throughout the eastern United States and southern Canada. Populations of this plant vary in their susceptibility to Erysiphe cruciferarum, a causal agent of powdery mildew disease in Brassicaceous plants. We examined whether there were biogeographic patterns in the distribution of resistance in invasive North American and native European populations of this plant. We grew plants from 78 invasive and 20 native populations and screened them for powdery mildew resistance in the greenhouse. We found that populations were mostly monomorphic for either resistance or susceptibility but that some polymorphic populations …

Larval Performance Of A Major Forest Pest On Novel Hosts And The Effect Of Stressors, Donnie Lee Peterson, Don Cipollini

Biological Sciences Faculty Publications

Novel hosts lacking a coevolutionary history with herbivores can often support improved larval performance over historic hosts; e.g., emerald ash borer [Agrilus planipennis (Fairmaire) Coleoptera: Buprestidae] on North American ash (Fraxinus spp.) trees. Whether trees are novel or ancestral, stress on plants increases emerald ash borer preference and performance. White fringetree [Chionanthus virginicus (L.) Lamiales: Oleaceae] and olive [Olea europaea (L.) Lamiales: Oleaceae] are closely related non-ash hosts that support development of emerald ash borer to adulthood, but their relative suitability as hosts and the impact of plant stress on larval success has not been well …

On The Potential For Saturated Buffers In Northwest Ohio To Remediate Nutrients From Agricultural Runoff, Stephen J. Jacquemin, Gregory J. Mcglinch, Theresa Dirksen, Angela Clayton

Biological Sciences Faculty Publications

Nutrient loading from nonpoint source runoff in the Midwest has emerged as one of the largest threats to water quality as the frequency of harmful algal blooms, hypoxic zones, and issues associated with human-resource interactions have risen abruptly over the past several decades. In this study, a saturated buffer ~500 m in length located in the western basin of the Lake Erie watershed was evaluated for its potential to reduce edge of field runoff and nutrient loading. Saturated buffers reduce runoff by routing subsurface tile drainage water into the riparian zone, providing an opportunity for drainage volume as well as …

The Role Of Manganese In Streptococcus Sanguinis, Tanya M. Puccio

Theses and Dissertations

Streptococcus sanguinis is primarily associated with oral health as a commensal bacterium. As an opportunistic pathogen, S. sanguinis is capable of colonizing heart valve vegetations, leading to the disease infective endocarditis. Previous studies from our lab have identified the high-affinity manganese transporter SsaACB as important for endocarditis virulence. The impact that manganese depletion has on S. sanguinis had never been evaluated and a secondary manganese transporter has not been identified. Thus, we employed the use of a fermentor to control large-scale growth over time and depleted manganese in an ΔssaACB mutant using a metal chelator, EDTA. The changes in …

A Discrete Age Structured Model Of Hantavirus In A Rodent Reservoir In Paraguay, Megan A. Rúa

Biological Sciences Faculty Publications

Many rodent-borne hantaviruses are zoonotic pathogens that can cause disease in humans through inhalation of aerosolized rodent excreta. To evaluate the prevalence of Jaborâ virus (JABV) over time within its rodent reservoir, Akodon montensis, we formulated a mathematical model with multiple rodent age classes and unique infection class progression features. We then parameterized the model with data collected from a survey of JABV harbored by Akodon montensis in the Mbaracayú Reserve in Paraguay. Our model incorporates three types of infection over the lifetime of the rodent as well as a recovered class. A new feature of the model allows transition …

The Missing Metric: An Evaluation Of Fungal Importance In Wetland Assessments, Megan A. Rúa

Biological Sciences Faculty Publications

To preserve wetland ecosystem function, federal and state agencies have developed assessment procedures to better manage remaining wetland areas. Currently, wetland assessments do not consider microorganisms when determining wetland quality. This is notable, because fungi are often the primary decomposers of organic material and thus important players in nutrient cycling. The objective of this study is to quantify how wetland quality, as measured using the Ohio Rapid Assessment Method (ORAM), relates to fungal community composition. We sampled soils from six depressional emergent marshes in Ohio belonging to each of the three ORAM quality categories, assessed soil physicochemical properties, and recovered …

Mathematics Saves Lives: Models And Signals Enabling Medicine And Biology, Raina Robeva

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Transient Dynamics Of Infection Transmission In An Intensive Care Unit, Christopher Short, Matthew S. Mietchen, Eric T. Lofgren

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Creating A Molecular Map Of The Pediatric Lung, Quinlen F. Marshall

Forum Lectures

The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types that exhibit remarkable heterogeneity. (Whitsett, JA. et al. Physiol. Rev, 2019). Surprisingly, few studies have solely focused on human lung development during this critical period, and many current studies of lung maturation rely on adult, murine, or diseased samples, limiting their insights and applicability to longitudinal pediatric lung development. Understanding the molecular and physiological nuances of pulmonary development has important clinical relevance, …

Temporal Gene Expression Of Mesenchymal Cells In The Pediatric Lung, Quinlen F. Marshall, Soumyaroop Bhattacharya, Gautam Bandyopadhyay, Ravi Misra, Thomas Mariani, Gloria Pryhuber

Chemistry Student Work

INTRODUCTION: The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types (Whitsett, JA. et al. Physiol. Rev, 2019). Murine models demonstrate that pulmonary mesenchymal cells exhibit remarkable heterogeneity in function and morphology during development, however, confirmation of their role is lacking in human neonates and early childhood (Guo, M. et al. Nat. Comm, 2019). In addition, many current human genomic studies of lung maturation suffer from limited sample size, limiting …

Biological Pathway Involvement In Melanoma Heterogeneity And Drug-Induced Resistance, Sarah V. Pack

STAR Program Research Presentations

Tumors develop resistance to numerous drug therapies, and this remains a major obstacle in treating many types of non-surgical cancers. Melanoma provides a good model system for studying drug resistance in cancer due to its high propensity to incur resistance after a significant initial response to a drug. Genes that are highly expressed in melanoma cancer cells have been studied, but in order to further understand the collective function of these highly expressed genes we must analyze gene sets, or pathways. A single gene’s function is rarely independent of other genes, and pathway analysis takes this into account.

Our objective …

Genetically Distinct Behavioral Modules Underlie Natural Variation In Thermal Performance Curves, Gregory W. Stegeman, Scott E. Baird, William S. Ryu, Asher D. Cutter

Biological Sciences Faculty Publications

Thermal reaction norms pervade organismal traits as stereotyped responses to temperature, a fundamental environmental input into sensory and physiological systems. Locomotory behavior represents an especially plastic read-out of animal response, with its dynamic dependence on environmental stimuli presenting a challenge for analysis and for understanding the genomic architecture of heritable variation. Here we characterize behavioral reaction norms as thermal performance curves for the nematode Caenorhabditis briggsae, using a collection of 23 wild isolate genotypes and 153 recombinant inbred lines to quantify the extent of genetic and plastic variation in locomotory behavior to temperature changes. By reducing the dimensionality of the …

Student-Faculty Collaborative Research Grant Report, Megan Bestwick

Post-Grant Reports

Mitochondria are essential organelles in most eukaryotic cells because of their role in metabolism and the production of ATP by the oxidative phosphorylation (OXPHOS) pathway, as well as other key cellular processes. Metal cofactors, such as copper (Cu) and iron (Fe), are incorporated into OXPHOS protein complexes of yeast located within the inner membrane of the mitochondria. Misincorporation or modulation of these available metals in mitochondrial enzymes leads to the production of reactive oxygen species (ROS). ROS are reactive molecules containing oxygen such as peroxides, superoxide, and hydroxyl radicals. Yeast are a good model for studying aging and the effect …

Lakeshore Modification Reduces Secondary Production Of Macroinvertebrates In Littoral But Not Deeper Zones, Marlene Pätzig, Yvonne Vadeboncoeur, Mario Brauns

Biological Sciences Faculty Publications

Littoral macroinvertebrates are an integral component of lake food webs, but their productivity may be affected by shoreline alteration. We hypothesized that human modification of lake shores simplifies habitat diversity, which, in turn, affects littoral macroinvertebrate production and patterns of depth–production relationships. Furthermore, we expected that lakeshore modification would favor nonnative species, potentially compensating for negative effects of lakeshore modification on production of native taxa. To test these ideas, we estimated benthic macroinvertebrate production in the upper littoral, middle littoral, and profundal zones of a large lowland lake (Lake Scharmützelsee) in Northeast Germany. We collected samples between April and November …

The Learning Loss Effect In Genetics: What Ideas Do Students Retain Or Lose After Instruction?, Amber Todd, William L. Romine

Biological Sciences Faculty Publications

Modern genetics is a relatively new domain, but it is increasingly important for students to have a firm grasp on the content, because genetic technologies are becoming more commonplace. In a previous study, we used the Learning Progression-based Assessment of Modern Genetics to assess high school students’ knowledge of genetics concepts after an intensive inquiry-based genetics instructional period. Given that this type of intensive inquiry-based instruction is unique, we are now investigating how students’ knowledge of genetics changes after instruction (i.e., learning loss effect). Using a six-measure longitudinal design, we found that students retained significant gains in five of the …

Green Tea Polyphenol Epigallocatechin-3-Gallate-Stearate Inhibits The Growth Of Streptococcus Mutans: A Promising New Approach In Caries Prevention, Amy Lynn Melok, Lee Lee, Siti Ayuni Mohamed Yussof, Tinchun Chu

Department of Biology Faculty Scholarship and Creative Works

Streptococcus mutans (S. mutans) is the main etiological bacteria present in the oral cavity that leads to dental caries. All of the S. mutans in the oral cavity form biofilms that adhere to the surfaces of teeth. Dental caries are infections facilitated by the development of biofilm. An esterified derivative of epigallocatechin-3-gallate (EGCG), epigallocatechin-3-gallate-stearate (EGCG-S), was used in this study to assess its ability to inhibit the growth and biofilm formation of S. mutans. The effect of EGCG-S on bacterial growth was evaluated with colony forming units (CFU) and log reduction; biofilm formation was qualitatively determined by Congo red assay, …

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …

Adaptive Divergence In A Defense Symbiosis Driven From The Top Down, Jeremy J. Heath, Patrick Abbot, John O. Stireman Iii

Biological Sciences Faculty Publications

Most studies of adaptive radiation in animals focus on resource competition as the primary driver of trait divergence. The roles of other ecological interactions in shaping divergent phenotypes during such radiations have received less attention. We evaluate natural enemies as primary agents of diversifying selection on the phenotypes of an actively diverging lineage of gall midges on tall goldenrod. In this system, the gall of the midge consists of a biotrophic fungal symbiont that develops on host-plant leaves and forms distinctly variable protective carapaces over midge larvae. Through field studies, we show that fungal gall morphology, which is induced by …

Studying Egfr Signaling Through Single Molecule Imaging And Computational Modeling, Emanuel Salazar Cavazos

Biomedical Sciences ETDs

Signaling through the Epidermal Growth Factor Receptor (EGFR) plays an important role in both physiological and cancer-related processes. In this work, single-molecule microscopy measurements and computational modeling were closely integrated to better understand the mechanisms that regulate EGFR signaling. Technical improvements were made over the previously described Single-Molecule Pull-down (SiMPull) assay to facilitate direct detection of the phosphorylation state of thousands of individual receptors, and thereby estimate both the fraction of receptors phosphorylated at specific tyrosine residues and the frequency of multisite phosphorylation. These improvements enabled the first direct detection of multisite phosphorylation on full-length Epidermal Growth Factor Receptor (EGFR), …

Sources And Fates Of Carbamyl Phosphate: A Labile Energy-Rich Molecule With Multiple Facets., Dashuang Shi, Ljubica Caldovic, Mendel Tuchman

Genomics and Precision Medicine Faculty Publications

Carbamyl phosphate (CP) is well-known as an essential intermediate of pyrimidine and arginine/urea biosynthesis. Chemically, CP can be easily synthesized from dihydrogen phosphate and cyanate. Enzymatically, CP can be synthesized using three different classes of enzymes: (1) ATP-grasp fold protein based carbamyl phosphate synthetase (CPS); (2) Amino-acid kinase fold carbamate kinase (CK)-like CPS (anabolic CK or aCK); and (3) Catabolic transcarbamylase. The first class of CPS can be further divided into three different types of CPS as CPS I, CPS II, and CPS III depending on the usage of ammonium or glutamine as its nitrogen source, and whether

Transcriptional Profiling Reveals Extraordinary Diversity Among Skeletal Muscle Tissues, Erin E. Terry, Xiping Zhang, Christy Hoffmann, Laura D. Hughes, Scott A. Lewis, Jiajia Li, Matthew J. Wallace, Lance A. Riley, Collin M. Douglas, Miguel A. Gutierrez-Monreal, Nicholas F. Lahens, Ming C. Gong, Francisco H. Andrade, Karyn A. Esser, Michael E. Hughes

Physiology Faculty Publications

Skeletal muscle comprises a family of diverse tissues with highly specialized functions. Many acquired diseases, including HIV and COPD, affect specific muscles while sparing others. Even monogenic muscular dystrophies selectively affect certain muscle groups. These observations suggest that factors intrinsic to muscle tissues influence their resistance to disease. Nevertheless, most studies have not addressed transcriptional diversity among skeletal muscles. Here we use RNAseq to profile mRNA expression in skeletal, smooth, and cardiac muscle tissues from mice and rats. Our data set, MuscleDB, reveals extensive transcriptional diversity, with greater than 50% of transcripts differentially expressed among skeletal muscle tissues. We detect …

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

Modeling And Analyzing An Optogenetic System For Photoactivatable Protein Dissociation, Anvin Thomas, James Schaff

Honors Scholar Theses

Computational modeling of cell-cell interactions can grant clues and can answer questions about an experiment, especially for observations about binding interactions and kinetics. This approach was used to investigate an interaction between a light-oxygen-voltage (LOV) domain and an engineered protein called Zdark (Zdk). The LOV domain is membrane-bound while Zdk is cytosolic. The LOV domain and Zdk bind strongly in dark (K_d 26.2 nM), and weakly upon exposure to blue light (K_d > 4 μM). Total internal reflection fluorescence (TIRF) images are acquired of Zdk, the fluorescent species bound to a mCherry tag, and the loss of fluorescence is …

Skeletal, Cardiac, And Respiratory Muscle Function And Histopathology In The P448lneo- Mouse Model Of Fkrp-Deficient Muscular Dystrophy., Qing Yu, Melissa Morales, Ning Li, Alexander G Fritz, Ren Ruobing, Anthony Blaeser, Ershia Francois, Qi-Long Lu, Kanneboyina Nagaraju, Christopher F Spurney

Genomics and Precision Medicine Faculty Publications

BACKGROUND: Fukutin-related protein (FKRP) mutations are the most common cause of dystroglycanopathies known to cause both limb girdle and congenital muscular dystrophy. The P448Lneo- mouse model has a knock-in mutation in the FKRP gene and develops skeletal, respiratory, and cardiac muscle disease.

METHODS: We studied the natural history of the P448Lneo- mouse model over 9 months and the effects of twice weekly treadmill running. Forelimb and hindlimb grip strength (Columbus Instruments) and overall activity (Omnitech Electronics) assessed skeletal muscle function. Echocardiography was performed using VisualSonics Vevo 770 (FujiFilm VisualSonics). Plethysmography was performed using whole body system (ADInstruments). Histological evaluations included …

Rest Upregulates Gremlin To Modulate Diffuse Intrinsic Pontine Glioma Vasculature, Shavali Shaik, Bridget Kennis, Shinji Maegawa, Keri Schadler, Yang Yanwen, Javad Nazarian, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive glial tumor that occurs in children. The extremely poor median and 5-year survival in children afflicted with DIPG highlights the need for novel biology-driven therapeutics. Here, we have implicated the chromatin remodeler and regulator of brain development called RE1 Silencing Transcription Factor (REST), in DIPG pathology. We show that REST protein is aberrantly elevated in at least 21% of DIPG tumors compared to normal controls. Its knockdown in DIPG cell lines diminished cell growth and decreased their tumorigenicity in mouse intracranial models. DIPGs are vascularized tumors and interestingly, REST loss in …