Biochemistry, Biophysics, and Structural Biology Commons^™

Recognition Of Extracellular Dna By Type Iv Pili Promotes Biofilm Formation By Clostridioides Difficile, Leslie A. Ronish, Ben Sidner, Yafan Yu, Kurt H. Piepenbrink

Department of Biochemistry: Faculty Publications

Clostridioides difficile is a Gram-positive bacillus, which is a frequent cause of gastrointestinal infections triggered by the depletion of the gut microbiome. Because of the frequent recurrence of these infections after antibiotic treatment, mechanisms of C. difficile persistence and recurrence, including biofilm formation, are of increasing interest. Previously, our group and others found that type IV pili, filamentous helical appendages polymerized from protein subunits, promoted microcolony and biofilm formation in C. difficile. In Gram-negative bacteria, the ability of type IV pili to mediate bacterial self-association has been explained through interactions between the pili of adjacent cells, but type …

Coordination Of Metal Center Biogenesis In Human Cytochrome C Oxidase, Eva Nývltová, Jonathan Dietz, Javier Seravalli, Oleh Khalimonchuk, Antoni Barrientos

Department of Biochemistry: Faculty Publications

Mitochondrial cytochrome c oxidase (CcO) or respiratory chain complex IV is a heme aa3- copper oxygen reductase containing metal centers essential for holo-complex biogenesis and enzymatic function that are assembled by subunit-specific metallochaperones. The enzyme has two copper sites located in the catalytic core subunits. The COX1 subunit harbors the CuB site that tightly associates with heme a3 while the COX2 subunit contains the binuclear CuA site. Here, we report that in human cells the CcO copper chaperones form macromolecular assemblies and cooperate with several twin CX9C proteins to control heme a biosynthesis and coordinate copper transfer sequentially to the …

The Role Of Irf-1 In Spontaneous Mouse Glioma, Aakash B. Vaidya

Theses and Dissertations

Glioblastoma Multiforme has been shown to be one of the deadliest primary brain cancers. One of the reasons why GBM is so deadly, is a unique immunosuppressive tumor microenvironment that promotes GBM growth and progression. Both astrocyte and microglia have been implicated in immunosuppression. In this study, we explored the role of Interferon Regulatory Factor 1 (IRF-1) in astrocytes and glioma cells on the growth of spontaneous glioma tumors. IRF-1 is regulated by the JAK/STAT pathway and induces expression of Programmed death ligand 1 (PD-L1). PD-L1 downregulates immune responses to glioma. We found that IRF-1 had no effect on spontaneous …

Building Digital Twins Of The Human Immune System: Toward A Roadmap, Reinhard Laubenbacher, Anna Niarakis, Tomas Helikar, G. An, B. Shapiro, R. S. Malik-Sheriff, T. J. Sego, P. Macklin, J. A. Glazier

Department of Biochemistry: Faculty Publications

Digital twins, customized simulation models pioneered in industry, are beginning to be deployed in medicine and healthcare, with some major successes, for instance in cardiovascular diagnostics and in insulin pump control. Personalized computational models are also assisting in applications ranging from drug development to treatment optimization. More advanced medical digital twins will be essential to making precision medicine a reality. Because the immune system plays an important role in such a wide range of diseases and health conditions, from fighting pathogens to autoimmune disorders, digital twins of the immune system will have an especially high impact. However, their development presents …

Addressing Barriers In Comprehensiveness, Accessibility, Reusability, Interoperability And Reproducibility Of Computational Models In Systems Biology, Anna Niarakis, Dagmar Waltemath, James Glazier, Falk Schreiber, Sarah M. Keating, David Nickerson, Claudine Chaouiya, Anne Siegel, Vincent Noël, Henning Hermjakob, Tomáš Helikar, Sylvain Soliman, Laurence Calzone

Department of Biochemistry: Faculty Publications

Computational models are often employed in systems biology to study the dynamic behaviours of complex systems. With the rise in the number of computational models, finding ways to improve the reusability of these models and their ability to reproduce virtual experiments becomes critical. Correct and effective model annotation in community-supported and standardised formats is necessary for this improvement. Here,we present recent efforts toward a common framework for annotated, accessible, reproducible and interoperable computational models in biology, and discuss key challenges of the field.

Scientists from different systems biology fields have long been developing community-driven guidelines and best practices for annotation, …

Development, Structure, And Mechanism Of Synthetic Antibodies That Target Claudin And Clostridium Perfringens Enterotoxin Complexes, Benjamin J. Orlando, Pawel K. Dominik, Sourav Roy, Chinemerem P. Ogbu, Satchal K. Erramilli, Anthony A. Kossiakoff, Alex J. Vecchio

Department of Biochemistry: Faculty Publications

Strains of Clostridium perfringens produce a two-domain enterotoxin (CpE) that afflicts humans and domesticated animals, causing prevalent gastrointestinal illnesses. CpE’s C-terminal domain (cCpE) binds cell surface receptors, followed by a restructuring of its N-terminal domain to form a membranepenetrating β-barrel pore, which is toxic to epithelial cells of the gut. The claudin family of membrane proteins are known receptors for CpE and also control the architecture and function of cell-cell contacts (tight junctions) that create barriers to intercellular molecular transport. CpE binding and assembly disables claudin barrier function and induces cytotoxicity via β-pore formation, disrupting gut homeostasis; however, a structural …

The Follicular Lymphoma Epigenome Regulates Its Microenvironment, Rada Amin, Mounia S. Braza

Department of Biochemistry: Faculty Publications

Follicular lymphoma (FL) is a B-cell non-Hodgkin lymphoma of germinal center (GC) origin with a distinctive tumor microenvironment (TME) and a unique spectrum of mutations. Despite the important therapeutic advances, FL is still incurable. During B-cell development, the GC reaction is a complex multistep process in which epigenetic regulators dynamically induce or suppress transcriptional programs. In FL, epigenetic gene mutations perturb the regulation of these programs, changing GC B-cell function and skewing differentiation towards tumor cells and altering the microenvironment interactions. FL pathogenesis and malignant transformation are promoted by epigenetic reprogramming of GC B cells that alters the immunological synapse …

Feedlot Diets Containing Different Starch Levels And Additives Change The Cecal Proteome Involved In Cattle’S Energy Metabolism And Inflammatory Response, Leone Campos Rocha, Andrey Sávio De Almeida Assunção, Renata Aparecida Martins, Victor Valério De Carvalho, Alexandre Perdigão2, Marília Afonso Rabelo Buzalaf, Jiri Adamec, Camila Pereira Braga, Danilo Domingues Millen, José Cavalcante Souza Vieira, Pedro De Magalhães Padilha

Department of Biochemistry: Faculty Publications

Diets for feedlot cattle must be a higher energy density, entailing high fermentable carbohydrate content. Feed additives are needed to reduce possible metabolic disorders. This study aimed to analyze the post-rumen effects of different levels of starch (25%, 35%, and 45%) and additives (monensin or a blend of essential oils and exogenous α-amylase) in diets for Nellore feedlot cattle. The cecum tissue proteome was analyzed via two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and then differentially expressed protein spots were identified with liquid chromatography–tandem mass spectrometry (LC–MS/MS). The use of blends of essential oils associated with α-amylase as a feed additive promoted …

Endothelial Cell-Specific Deletion Of A Microrna Accelerates Atherosclerosis, Dafeng Yang, Stefan Haemmig, Jingshu Chen, Michael Mccoy, Henry S. Cheng, Haoyang Zhou, Daniel Pérez-Cremades, Xiao Cheng, Xinghui Sun, Jorge Haneo-Mejia, Shamsudheen K. Vellarikkal, Rajat M. Gupta, Victor Barrera, Mark W. Feinberg

Department of Biochemistry: Faculty Publications

Background and aims: Chronic vascular endothelial inflammation predisposes to atherosclerosis; however, the cell-autonomous roles for endothelial-expressing microRNAs (miRNAs) are poorly understood in this process. MiR-181b is expressed in several cellular constituents relevant to lesion formation. The aim of this study is to examine the role of genetic deficiency of the miR-181b locus in endothelial cells during atherogenesis.

Methods and Results: Using a proprotein convertase subtilisin/kexin type 9 (PCSK9)-induced atherosclerosis mouse model, we demonstrated that endothelial cell (EC)-specific deletion of miR-181a2b2 significantly promoted atherosclerotic lesion formation, cell adhesion molecule expression, and the influx of lesional macrophages in the vessel wall. Yet, …

Analysis Of The Antimicrobial Activity Of The Novel Chemotherapeutic Drug, Tpp1, Against Pseudomonas Aeruginosa And The Hydrogel Delivery Of Water-Soluble Antimicrobial Compounds, Alex Gasper

Senior Independent Study Theses

Cancer is one of the leading causes of death in the world, and it is commonly linked with bacterial infections that often complicate treatments. Recently, chemotherapeutics have been developed that are able to act as anti-cancer agents using delocalized lipophilic cations (DLCs) that are able to specifically target mitochondrial membranes of cancer cells. TPP1 is a newly developed chemotherapeutic drug that has activity against bladder cancer and melanoma cell lines in vitro. In order to determine if TPP1 has antimicrobial activity, TPP1 was tested against a common bacteria, Pseudomonas aeruginosa, to determine if antimicrobial activity was present. This testing was …

A Link Between Methylglyoxal And Heart Failure During Hiv-1 Infection, Prasanta K. Dasg, Fadhel A. Alomar, Jesse L. Cox, Joellyn Mcmillan, Bryan T. Hackfort, Edward Makarov, Brenda Morsey, Howard S. Fox, Howard E. Gendelman, Santhi Gorantla, Keshore R. Bidasee

Department of Biochemistry: Faculty Publications

Early-onset heart failure (HF) continues to be a major cause of morbidity and mortality in people living with human immunodeficiency virus type one (HIV-1) infection (PLWH), yet the molecular causes for this remain poorly understood. Herein NOD.Cg- Prkdc^scidIl2rg^tm1Wjl/SzJ humanized mice (Hu-mice), plasma from PLWH, and autopsied cardiac tissues from deceased HIV seropositive individuals were used to assess if there is a link between the glycolysis byproduct methylglyoxal (MG) and HF in the setting of HIV-1 infection. At five weeks post HIV infection, Hu-mice developed grade III-IV diastolic dysfunction (DD) with an associated two-fold increase in plasma …

The Application Of Mathematical Optimization And Flavor-Detection Technologies For Modeling Aroma Of Hops, Yutong Liu

Department of Food Science and Technology: Dissertations, Theses, and Student Research

In recent years, proprietary hops (Citra, Simcoe, and Mosaic) become the most sought-after hops among brewers due to their excellent aroma. However, they are restricted to the owners unless other growers purchase the costly licensing agreements. Many public hops are available to the growers without any additional costs, but their aroma is difficult to match to the proprietary hops. Although proprietary and public hop varieties are unique in their aroma profiles, all hops varieties contain similar volatile compounds, merely differ in the quantity of different individual compounds. The main objective of this thesis was to investigate the feasibility of matching …

Charting A New Frontier Integrating Mathematical Modeling In Complex Biological Systems From Molecules To Ecosystems, Katharine A. White, Kira D. Mcentire, Nicole R. Buan, Lecia Robinson, Elisar Barbar

Department of Biochemistry: Faculty Publications

Advances in quantitative biology data collection and analysis across scales (molecular, cellular, organismal, and ecological) have transformed how we understand, categorize, and predict complex biological systems. This surge of quantitative data creates an opportunity to apply, develop, and evaluate mathematical models of biological systems and explore novel methods of analysis. Simultaneously, thanks to increased computational power, mathematicians, engineers, and physical scientists have developed sophisticated models of biological systems at different scales. Novel modeling schemes can offer deeper understanding of principles in biology, but there is still a disconnect between modeling and experimental biology that limits our ability to fully realize …

Stabilin Receptors Clear Lps And Control Systemic Inflammation, Fatima Cabral, Mustafa Al-Rahem, John Skaggs, Thushara A. Thomas, Naresh Kumar, Qian Wu, Paolo Fadda, Lianbo Yu, John M. Robinson, Jonghan Kim, Ekta Pandey, Xinghui Sun, Wael N. Jarjour, Murugesan V.S. Rajaram, Edward N. Harris, Latha P. Ganesan

Department of Biochemistry: Faculty Publications

Lipopolysaccharides (LPSs) cause lethal endotoxemia if not rapidly cleared from blood circulation. Liver sinusoidal endothelial cells (LSEC) systemically clear LPS by unknown mechanisms. We discovered that LPS clearance through LSEC involves endocytosis and lysosomal inactivation via Stabilin-1 and 2 (Stab1 and Stab2) but does not involve TLR4. Cytokine production was inversely related to clearance/endocytosis of LPS by LSEC. When exposed to LPS, Stabilin double knockout mice (Stab DK) and Stab1 KO, but not Stab2 KO, showed significantly enhanced systemic inflammatory cytokine production and early death compared with WT mice. Stab1 KO is not significantly different from Stab DK in circulatory …

Binding Affinity And Interaction Of Sars-Cov-2 Epitopes With Major Histocompatibility Complex, Sareena Kandavalli, James Stewart, Mohammed A. Halim

Symposium of Student Scholars

SARS CoV-2 has been affecting the world since 2019. It caused 245 million cases of infection and around 5 million deaths worldwide. The most important strategies for the development of vaccines against SARS-CoV-2 are inactivated or weakened virus, replicating or non-replicating viral vector-based approaches, DNA, RNA, virus particle like approaches and epitope-based approaches. The epitope-based approach is rapid, accurate, cost-effective, and reliable against pathogens. By presenting epitopes (antigen peptides) on antigen-presenting cells (APCs), the major histocompatibility complex (MHC), also recognized as the human leukocyte antigen (HLA) system in humans, plays an essential role in triggering T-cell immune responses. The focus …

Computational Simulation Of The Lung Doses Of Air-Borne Fine And Ultrafine Particles Inhaled By Humans At Industrial Workplaces, Mohammed Ali

Technology Faculty Publications and Presentations

This study correlates computational predictions with in-vivo experimental results of inhaled fine and ultrafine particulate matters (PMs) transport, dissemination, and deposition in the human respiratory airways. Epidemiological studies suggest that workplace exposure of anthropogenic pollutant PMs as a risk factor for increased susceptibility to acute broncho-pulmonary infections. However, investigations on detailed human inhalation and PM transport processes are restrictive from time, cost, and ethical perspectives. To overcome this problem, computational simulation of particle deposition based on the Multiple Path Particle Dosimetry (MPPD) model was employed. Here, the physical, mechanical, and electrical properties of PMs of carbon black and nanoparticles from …

Physiological Roles Of Mammalian Transmembrane Adenylyl Cyclase Isoforms, Katrina F. Ostrom, Justin E. Lavigne, Tarsis F. Brust, Roland Seifert, Carmen Dessauer, Val J. Watts, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Adenylyl cyclases (ACs) catalyze the conversion of ATP to the ubiquitous second messenger cAMP. Mammals possess nine isoforms of transmembrane ACs, dubbed AC1-9, that serve as major effector enzymes of G protein-coupled receptors. The transmembrane ACs display varying expression patterns across tissues, giving potential for them having a wide array of physiologic roles. Cells express multiple AC isoforms, implying that ACs have redundant functions. Furthermore, all transmembrane ACs are activated by Gα_s so it was long assumed that all ACs are activated by Gα_s-coupled GPCRs. AC isoforms partition to different microdomains of the plasma membrane and form …

Dynamic Evolution And Correlation Between Metabolites And Microorganisms During Manufacturing Process And Storage Of Fu Brick Tea, Jing Li, Ran Xu, Joseph Brake, Lizeng Cheng, Jie Wu, Xiaobin Wu

Department of Biochemistry: Faculty Publications

Fu brick tea (FBT) is one of the major brands of dark tea. Microbial fermentation is considered the key step in the development of the special characteristics of FBT. The systemic corelationship of the microbiome and metabolomics during manufacture of Fu brick tea is not fully understood. In this study, we comprehensively explored the microbiome and metabolite dynamic evolution during the FBT manufacturing processes, and revealed decisive factors for the quality and safety of FBT based on the grouped methods of metabolomics combined with biochemical measurements, microbiome sequencing combined with quantitative polymerase chain reaction (PCR), and multiplex analysis. Both the …

Recent Applications Of Quantitative Systems Pharmacology And Machine Learning Models Across Diseases, Sara Sadat Aghamiri1, Rada Amin, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Quantitative systems pharmacology (QSP) is a quantitative and mechanistic platform describing the phenotypic interaction between drugs, biological networks, and disease conditions to predict optimal therapeutic response. In this meta-analysis study, we review the utility of the QSP platform in drug development and therapeutic strategies based on recent publications (2019–2021). We gathered recent original QSP models and described the diversity of their applications based on therapeutic areas, methodologies, software platforms, and functionalities. The collection and investigation of these publications can assist in providing a repository of recent QSP studies to facilitate the discovery and further reusability of QSP models. Our review …

Purification And Initial Biochemical Characterization Of Atp:Cob(I)Alamin Adenosyltransferase (Eutt) Enzyme Of Salmonella Enterica, Nicole R. Buan, Jorge C. Escalante-Semerena

Department of Biochemistry: Faculty Publications

ATP:cob(I)alamin adenosyltransferase (EutT) of Salmonella enterica was overproduced and enriched to ~70% homogeneity, and its basic kinetic parameters were determined. Abundant amounts of EutT protein were produced, but all of it remained insoluble. Soluble active EutT protein (~70% homogeneous) was obtained after treatment with detergent. Under conditions in which cobalamin (Cbl) was saturating, K_m(ATP) = 10 μM, k_cat = 0.03 s^–1, and V_max = 54.5 nM min^–1. Similarly, under conditions in which MgATPwas saturating,K_m(Cbl)= 4.1μM, k_cat = 0.06 s^–1, andV_{max …}

The Simulation Experiment Description Markup Language (Sed-Ml): Language Specification For Level 1 Version 4, Lucian P. Smith,, Frank T. Bergmann, Alan Garny, Tomáš Helikar, Jonathan Karr, David Nickerson,, Herbert Sauro, Dagmar Waltemath, Matthias König

Department of Biochemistry: Faculty Publications

Computational simulation experiments increasingly inform modern biological research, and bring with them the need to provide ways to annotate, archive, share and reproduce the experiments performed. These simulations increasingly require extensive collaboration among modelers, experimentalists, and engineers. The Minimum Information About a Simulation Experiment (MIASE) guidelines outline the information needed to share simulation experiments. SED-ML is a computer-readable format for the information outlined by MIASE, created as a community project and supported by many investigators and software tools. The first versions of SED-ML focused on deterministic and stochastic simulations of models. Level 1 Version 4 of SED-ML substantially expands these …

Liquid And Semisolid Lubricant Compositions , Methods Of Making , And Uses Thereof, Diana Berman, Kent Dean Chapman, Tervor Bradley Romsdahl, Edgar Benjamin Cahoon, Robert Earl Minto, Chunyu Zhang

Department of Biochemistry: Faculty Publications

Various liquid and semisolid lubricant compositions are provided, in particular lubricant compositions containing oil from the seeds of the Brassicaceae Orychophragmus violaceus, preferably those that have been esterified with one or more fatty acids such as palmitoleic acid, oleic acid, linoleic acid, lauric acid, palmitic acid, stearic acid, or a combination thereof. In various aspects, lubricant compositions are provided that include a petroleum or a synthetic base oil and about 40 % or less by weight of a liquid lubricant composition containing oil from the seeds of the Brassicaceae Orychophragmus violaceus preferably those that have been esterified with one …

Mitochondrial Contact Site And Cristae Organizing System (Micos) Machinery Supports Heme Biosynthesis By Enabling Optimal Performance Of Ferrochelatase, Jonathan V. Dietz, Mathilda M. Willoughby, Robert B. Piel, Teresa A. Ross, Iryna Bohovych, Hannah G. Addis, Jennifer L. Fox, William N. Lanzilotta, Harry A. Dailey, James A. Wohlschlegel, Amit R. Reddi, Amy E. Medlock, Oleh Khalimonchuk

Department of Biochemistry: Faculty Publications

Heme is an essential cofactor required for a plethora of cellular processes in eukaryotes. In metazoans the heme biosynthetic pathway is typically partitioned between the cytosol and mitochondria, with the first and final steps taking place in the mitochondrion. The pathway has been extensively studied and its biosynthetic enzymes structurally characterized to varying extents. Nevertheless, understanding of the regulation of heme synthesis and factors that influence this process in metazoans remains incomplete. Therefore, we investigated the molecular organization as well as the physical and genetic interactions of the terminal pathway enzyme, ferrochelatase (Hem15), in the yeast Saccharomyces cerevisiae. Biochemical and …

Oxidation Alters The Architecture Of The Phenylalanyl-Trna Synthetase Editing Domain To Confer Hyperaccuracy, Pooja Srinivas, Rebecca E. Steiner, Ian J. Pavelich, Ricardo Guerrera-Ferreira, Puneet Juneja, Michael Ibba, Christine M. Dunham

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

High fidelity during protein synthesis is accomplished by aminoacyl-tRNA synthetases (aaRSs). These enzymes ligate an amino acid to a cognate tRNA and have proofreading and editing capabilities that ensure high fidelity. Phenylalanyl-tRNA synthetase (PheRS) preferentially ligates a phenylalanine to a tRNA^Phe over the chemically similar tyrosine, which differs from phenylalanine by a single hydroxyl group. In bacteria that undergo exposure to oxidative stress such as Salmonella enterica serovar Typhimurium, tyrosine isomer levels increase due to phenylalanine oxidation. Several residues are oxidized in PheRS and contribute to hyperactive editing, including against mischarged Tyr-tRNA^Phe, despite these oxidized residues not …

The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber

Dissertations, Theses, and Capstone Projects

Light provides organisms with energy and spatiotemporal information. To survive and adapt, organisms have developed the ability to sense light to drive biochemical effects that underlie vision, entrainment of circadian rhythm, stress response, virulence, and many other important molecularly driven responses. Blue-light sensing Light-Oxygen-Voltage (LOV) domains are ubiquitous across multiple kingdoms of life and modulate various physiological events via diverse effector domains. Using a small molecule flavin chromophore, the LOV domain undergoes light-dependent structural changes leading to activation or repression of these catalytic and non-catalytic effectors. In silico analyses of high-throughput genomic sequencing data has led to the marked expansion …

Conformation Of The Protein-Free Spliceosomal U2-U6 Snrna Complex And Remodeling By Mg2+ And Proteins, Huong Chu

Dissertations, Theses, and Capstone Projects

Splicing of precursor messenger RNA is an essential process in eukaryotes in which the non-coding regions (introns) are removed and coding regions (exons) ligated together to form a mature mRNA. This process is catalyzed by a multi-mega Dalton ribonucleoprotein complex called the spliceosome, which is assembled from five small nuclear ribonucleoproteins (snRNP) in the form of RNA-protein complexes (U1, U2, U4, U5 and U6) and hundreds of proteins. U2 and U6 small nuclear (sn)RNAs are the only snRNAs directly implicated in catalyzing the splicing of pre-mRNA, but assembly and rearrangement steps prior to catalysis require numerous proteins. Previous studies have …

Dual Control Of One Component Signaling: Mechanistic And Structural Insights Into El222 Active States, Uthama Phani R. Edupuganti

Dissertations, Theses, and Capstone Projects

Photoreceptors play a crucial role in signal transduction as specialized proteins which sense light as environmental stimuli and transduce the signal to control of downstream functions. Here we focus our attention on one class of these proteins, the Light-Oxygen-Voltage (LOV) domain, which is sensitive to blue light via an internally-bound flavin chromophore. Since their initial discovery in plant phototropins, many details of their photochemistry, chromophore interactions, and use with a diverse set of functional effectors have been described. However, several key details, especially a comprehensive understanding of signaling mechanism and its regulation, still remain elusive due in part to the …

Down The Iron Path: Mitochondrial Iron Homeostasis And Beyond, Jonathan Dietz, Jennifer L. Fox, Oleh Khalimonchuk

Department of Biochemistry: Faculty Publications

Cellular iron homeostasis and mitochondrial iron homeostasis are interdependent. Mitochondria must import iron to form iron–sulfur clusters and heme, and to incorporate these cofactors along with iron ions into mitochondrial proteins that support essential functions, including cellular respiration. In turn, mitochondria supply the cell with heme and enable the biogenesis of cytosolic and nuclear proteins containing iron–sulfur clusters. Impairment in cellular or mitochondrial iron homeostasis is deleterious and can result in numerous human diseases. Due to its reactivity, iron is stored and trafficked through the body, intracellularly, and within mitochondria via carefully orchestrated processes. Here, we focus on describing the …

A Multi-Approach And Multi-Scale Platform To Model Cd4+ T Cells Responding To Infections, Kenneth Y. Wertheim, Bhanwar Lal Puniya, Alyssa La Fleur, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Immune responses rely on a complex adaptive system in which the body and infections interact at multiple scales and in different compartments. We developed a modular model of CD4+ T cells, which uses four modeling approaches to integrate processes at three spatial scales in different tissues. In each cell, signal transduction and gene regulation are described by a logical model, metabolism by constraint-based models. Cell population dynamics are described by an agent-based model and systemic cytokine concentrations by ordinary differential equations. A Monte Carlo simulation algorithm allows information to flow efficiently between the four modules by separating the time scales. …

Case 51: Purification Of A Transferase Involved In The Production Of Physiologically Important Glycoproteins, Dr. Kathleen Cornely

Chemistry & Biochemistry Case Studies

A transferase involved in post-translational glycosylation of a physiologically important glycoprotein is purified and characterized.