Biochemistry Commons^™

Dna Uptake By Type Iv Filaments, Kurt H. Piepenbrink

Department of Biochemistry: Faculty Publications

Bacterial uptake of DNA through type IV filaments is an essential component of natural competence in numerous gram-positive and gram-negative species. Recent advances in the field have broadened our understanding of the structures used to take up extracellular DNA. Here, we review seminal experiments in the literature describing DNA binding by type IV pili, competence pili and the flp pili of Micrococcus luteus; collectively referred to here as type IV filaments. We compare the current state of the field on mechanisms of DNA uptake for these three appendage systems and describe the current mechanistic understanding of both DNA-binding and …

Student Understanding Of Dna Structure–Function Relationships Improves From Using 3d Learning Modules With Dynamic 3d Printed Models, Michelle E. Howell, Christine S. Booth, Sharmin M. Sikich, Tomáš Helikar, Rebecca Roston, Brain A. Couch, Karin Van Dijk

Department of Biochemistry: Faculty Publications

Understanding the relationship between molecular structure and function represents an important goal of undergraduate life sciences. Although evidence suggests that handling physical models supports gains in student understanding of structure–function relationships, such models have not been widely implemented in biochemistry classrooms. Three-dimensional (3D) printing represents an emerging cost-effective means of producing molecular models to help students investigate structure–function concepts. We developed three interactive learning modules with dynamic 3D printed models to help biochemistry students visualize biomolecular structures and address particular misconceptions. These modules targeted specific learning objectives related to DNA and RNA structure, transcription factor-DNA interactions, and DNA supercoiling dynamics. …

Winter Hardiness Of Miscanthus (Iii): Genome‐Wide Association And Genomic Prediction For Overwintering Ability In Miscanthus Sinensis, Hongxu Dong, Lindsay V. Clark, Alexander E. Lipka, Joe E. Brummer, Katarzyna Glowacka, Megan C. Hall, Kweon Heo, Xiaoli Jin, Junhua Peng, Toshihiko Yamada, Bimal Kumar Ghimire, Ji Hye Yoo, Chang Yeon Yu, Hua Zhao, Stephen P. Long, Erik J. Sacks

Department of Biochemistry: Faculty Publications

Overwintering ability is an important selection criterion for Miscanthus breeding in temperate regions. Insufficient overwintering ability of the currently leading Miscanthus biomass cultivar, M. ×giganteus (M×g) ‘1993–1780’, in regions where average annual minimum temperatures are −26.1°C (USDA hardiness zone 5) or lower poses a pressing need to develop new cultivars with superior cold tolerance. To facilitate breeding of Miscanthus, this study characterized phenotypic and genetic variation of overwintering ability in an M. sinensis germplasm panel consisting of 564 accessions, evaluated in field trials at three locations in North America and two in Asia. Genome‐wide association (GWA) and genomic …

Chronic Alcohol Exposure Alters Circulating Insulin And Ghrelin Levels: Role Of Ghrelin In Hepatic Steatosis, Karuna Rasineni, Paul G. Thomes, Jacy L. Kubik, Edward N. Harris, Kusum K. Kharbanda, Carol A. Casey

Department of Biochemistry: Faculty Publications

Fatty liver is the earliest response of the liver to excessive ethanol consumption. Central in the development of alcoholic steatosis is increased mobilization of nonesterified free fatty acids (NEFAs) to the liver from the adipose tissue. In this study, we hypothesized that ethanol-induced increase in ghrelin by impairing insulin secretion, could be responsible for the altered lipid metabolism observed in adipose and liver tissue. Male Wistar rats were fed for 5–8 wk with control or ethanol Lieber-DeCarli diet, followed by biochemical analyses in serum and liver tissues. In addition, in vitro studies were conducted on pancreatic islets isolated from experimental …

The Mitochondrial Nad+ Transporter (Ndt1) Plays Important Roles In Cellular Nad+ Homeostasis In Arabidopsis Thaliana, Izabel De Souza Chaves, Elias Feitosa-Araujo, Alexandra Florian, David B. Medeiros, Paula Da Fonseca-Pereira, Lennart Charton, Elmien Heyneke, Jorge A. C. Apfata, Marcel V. Pires, Tabea Mettler-Altmann, Wagner L. Arajuo, H. Ekkehard Neuhaus, Ferdinando Palmieri, Toshihiro Obata, Andreas P. M. Weber, Nicole Linka, Alisdair R. Femie, Adriano Nunes-Nesi

Department of Biochemistry: Faculty Publications

Nicotinamide adenine dinucleotide (NAD⁺) is an essential coenzyme required for all living organisms. In eukaryotic cells, the final step of NAD⁺ biosynthesis is exclusively cytosolic. Hence, NAD⁺ must be imported into organelles to support their metabolic functions. Three NAD⁺ transporters belonging to the mitochondrial carrier family (MCF) have been biochemically characterized in plants. AtNDT1 (At2g47490), focus of the current study, AtNDT2 (At1g25380), targeted to the inner mitochondrial membrane, and AtPXN (At2g39970), located in the peroxisomal membrane. Although AtNDT1 was presumed to reside in the chloroplast …

Acyltransferases And Methods Of Using, Edgar Cahoon, Umidjon Iskandarov, Hae Jin Kim, Jillian Collins-Silva

Department of Biochemistry: Faculty Publications

Provided herein are novel acyltransferases and methods of using such novel acyltransferases in making medium - chain fatty acids.

Charting A New Frontier Of Science By Integrating Mathematical Modeling To Understand And Predict Complex Biological Systems, Katharine White, Kira Mcentire, Nicole R. Buan, Kingshuk Ghosh, Lecia Robinson, Elisar Barbar

Department of Biochemistry: Faculty Publications

Biological systems are staggeringly complex. To untangle this complexity and make predictions about biological systems is a continuous goal of biological research. One approach to achieve these goals is to emphasize the use of quantitative measures of biological processes. Advances in quantitative biology data collection and analysis across scales (molecular, cellular, organismal, ecological) has transformed how we understand, categorize, and predict complex biological systems. Simultaneously, thanks to increased computational power, mathematicians, engineers and physical scientists -- collectively termed theoreticians -- have developed sophisticated models of biological systems at different scales. But there is still a disconnect between the two fields. …

Fatty Acid Transporter 2 Reprograms Neutrophils In Cancer, Filippo Veglia, Vladimir A. Tyurin, Maria Blasi, Alessandra De Leo, Andrew Kossenkov, Laxminarasimha Donthireddy, To Tsun Ki Jerrick, Zach Schug, Subhasree Basu, Fang Wang, Emanuela Ricciotti, Concetta C. Dirusso, Maureen E. Murphy, Robert H. Vonderheide, Paul M. Lieberman, Charles Mulligan, Brian Nam, Neil Hockstein, Gregory Masters, Michael Guarino, Cindy Lin, Yulia Nefedova, Paul N. Black, Valerian E, Kagan, Dmitry Gabrilovich

Department of Biochemistry: Faculty Publications

Polymorphonuclear myeloid derived suppressor cells (PMN-MDSC) are pathologically activated neutrophils that are critically important for the regulation of immune responses in cancer. They contribute to the failure of cancer therapies and are associated with poor clinical outcomes. Despite the recent advances in understanding of the PMN-MDSC biology, the mechanisms responsible for pathological activation of neutrophils are not well defined, which limits selective targeting of these cells. Here, we report that mouse and human PMN-MDSC exclusively up-regulate fatty acid transporter protein 2 (FATP2). Over-expression of FATP2 in PMN-MDSC was controlled by GM-CSF, through the activation of STAT5 transcription factor. Deletion of …

Arsenite Exposure Suppresses Adipogenesis, Mitochondrial Biogenesis And Thermogenesis Via Autophagy Inhibition In Brown Adipose Tissue, Jiyoung Bae, Yura Jang, Heejeong Kim, Kalika Mahato, Cameron Schaecher, Issac M. Kim, Eunju Kim, Seung-Hyun Ro

Department of Biochemistry: Faculty Publications

Arsenite, a trivalent form of arsenic, is an element that occurs naturally in the environment. Humans are exposed to high dose of arsenite through consuming arsenite-contaminated drinking water and food, and the arsenite can accumulate in the human tissues. Arsenite induces oxidative stress, which is linked to metabolic disorders such as obesity and diabetes. Brown adipocytes dissipating energy as heat have emerging roles for obesity treatment and prevention. therefore, understanding the pathophysiological role of brown adipocytes can provide effective strategies delineating the link between arsenite exposure and metabolic disorders. Our study revealed that arsenite significantly reduced differentiation of murine brown …

The Structure Of Pila From Acinetobacter Baumannii Ab5075 Suggests A Mechanism For Functional Specialization In Acinetobacter Type Iv Pili, Leslie A. Ronish, Erik Lillehoj, James K. Fields, Eric J. Sundberg, Kurt Piepenbrink

Department of Biochemistry: Faculty Publications

Type IV pili (T4P) are bacterial appendages composed of protein subunits, called pilins, noncovalently assembled into helical fibers. T4P are essential, in many bacterial species, for processes as diverse as twitching motility, natural competence, biofilm or microcolony formation, and host cell adhesion. The genes encoding type IV pili are found universally in the Gram-negative, aerobic, nonflagellated, and pathogenic coccobacillus Acinetobacter baumannii, but there is considerable variation in PilA, the major protein subunit, both in amino acid sequence and in glycosylation patterns. Here we report the X-ray crystal structure of PilA from AB5075, a recently characterized, highly virulent isolate, at …

Methanogens: Pushing The Boundaries Of Biology, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Methanogens are anaerobic archaea that grow by producing methane gas. These microbes and their exotic metabolism have inspired decades of microbial physiology research that continues to push the boundary of what we know about how microbes conserve energy to grow. The study of methanogens has helped to elucidate the thermodynamic and bioenergetics basis of life, contributed our understanding of evolution and biodiversity, and has garnered an appreciation for the societal utility of studying trophic interactions between environmental microbes, as methanogens are important in microbial conversion of biogenic carbon into methane, a high-energy fuel. This review discusses the theoretical basis for …

Methanogens: Pushing The Boundaries Of Biology, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Methanogens are anaerobic archaea that grow by producing methane gas. These microbes and their exotic metabolism have inspired decades of microbial physiology research that continues to push the boundary of what we know about how microbes conserve energy to grow. The study of methanogens has helped to elucidate the thermodynamic and bioenergetics basis of life, contributed our understanding of evolution and biodiversity, and has garnered an appreciation for the societal utility of studying trophic interactions between environmental microbes, as methanogens are important in microbial conversion of biogenic carbon into methane, a high-energy fuel. This review discusses the theoretical basis for …

Combining Mass Spectrometry And Nmr Improves Metabolite Detection And Annotation, Fatema Bhinderwala, Nishikant Wase, Concetta Dirusso, Robert Powers

Department of Biochemistry: Faculty Publications

Despite inherent complementarity, nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) are routinely separately employed to characterize metabolomics samples. More troubling is the erroneous view that metabolomics is better served by exclusively utilizing MS. Instead, we demonstrate the importance of combining NMR and MS for metabolomics by using small chemical compound-treatments of Chlamydomonas reinhardtii as an illustrative example. A total of 102 metabolites were detected (82 by GC-MS, 20 by NMR and 22 by both techniques). Out of these 47 metabolites of interest were identified, where 14 metabolites were uniquely identified by NMR and 16 metabolites were uniquely identified …

Mouse Genome-Wide Association Studies And Systems Genetics Uncover The Genetic Architecture Associated With Hepatic Pharmacokinetic And Pharmacodynamic Properties Of A Constrained Ethyl Antisense Oligonucleotide Targeting Malat1, Elaine Pirie, Shayoni Ray, Calvin Pan, Wuxia Fu, Andrew F. Powers, Danielle Polikoff, Colton M. Miller, Katrina M. Kudrna, Edward N. Harris, Aldons J. Lusis, Rosanne M. Crooke, Richard G. Lee

Department of Biochemistry: Faculty Publications

Antisense oligonucleotides (ASOs) have demonstrated variation of efficacy in patient populations. This has prompted our investigation into the contribution of genetic architecture to ASO pharmacokinetics (PK) and pharmacodynamics (PD). Genome wide association (GWA) and transcriptomic analysis in a hybrid mouse diversity panel (HMDP) were used to identify and validate novel genes involved in the uptake and efficacy of a single dose of a Malat1 constrained ethyl (cEt) modified ASO. The GWA of the HMDP identified two significant associations on chromosomes 4 and 10 with hepatic Malat1 ASO concentrations. Stabilin 2 (Stab2) and vesicle associated membrane protein 3 ( …

Induction Of Oil Accumulation By Heat Stress Is Metabolically Distinct From N Stress In The Green Microalgae Coccomyxa Subellipsoidea C169, James W. Allen, Rahul Tevatia, Yaşar Demirel, Concetta C. Dirusso, Paul N. Black

Department of Biochemistry: Faculty Publications

Algae are often promoted as feedstock organisms to produce a sustainable petroleum fossil fuel alternative. However, to induce lipid accumulation most often requires a severe stress that is difficult to induce in large batch cultures. The objective of this study is to analyze and mathematically model heat stress on growth, chlorophyll content, triacylglyceride, and starch synthesis in algae. We initially screened 30 algal species for the most pronounced induction of lipid droplets from heat stress using confocal microscopy and mass spectroscopy techniques. One species, Coccomyxa subellipsoidea C169, was selected and subjected to further biochemical analyses using a jacketed bioreactor amended …

Identification Of Biologically Essential Nodes Via Determinative Power In Logical Models Of Cellular Processes, Trevor Pentzien, Bhanwar L. Puniya, Tomas Helikar, Mihaela T. Matache

Department of Biochemistry: Faculty Publications

A variety of biological networks can bemodeled as logical or Boolean networks. However, a simplification of the reality to binary states of the nodes does not ease the difficulty of analyzing the dynamics of large, complex networks, such as signal transduction networks, due to the exponential dependence of the state space on the number of nodes. This paper considers a recently introduced method for finding a fairly small subnetwork, representing a collection of nodes that determine the states of most other nodes with a reasonable level of entropy. The subnetwork contains the most determinative nodes that yield the highest information …

Establishing Hematology And Serum Chemistry Reference Intervals For Wild Hawaiian Monk Seals (Neomonachus Schauinslandi), Angela C. Kaufman, Stacie J. Robinson, Dori L. Borjesson, Michelle Barbieri, Charles L. Littnan

United States Department of Commerce: Staff Publications

Hematology and serum chemistry reference intervals have been previously established for the endangered Hawaiian monk seal (Neomonachus schauinslandi) as an imperative measure for health assessments. Monitoring the health of the wild population depends upon reference intervals that are context specific; hence we developed reference intervals from fresh samples, as opposed to frozen, from wild monk seals. This study builds on the number of parameters from previous efforts by using samples collected between 2004 and 2015 from wild monk seals. Blood samples were analyzed by a single veterinary diagnostic laboratory within 24 hr of collection from apparently healthy, wild …

Lipid Transport Required To Make Lipids Of Photosynthetic Membranes, Evan Labrant, Allison C. Barnes, Rebecca Roston

Department of Biochemistry: Faculty Publications

Photosynthetic membranes provide much of the usable energy for life on earth. To produce photosynthetic membrane lipids, multiple transport steps are required, including fatty acid export from the chloroplast stroma to the endoplasmic reticulum, and lipid transport from the endoplasmic reticulum to the chloroplast envelope membranes. Transport of hydrophobic molecules through aqueous space is energetically unfavorable and must be catalyzed by dedicated enzymes, frequently on specialized membrane structures. Here, we review photosynthetic membrane lipid transport to the chloroplast in the context of photosynthetic membrane lipid synthesis. We independently consider the identity of transported lipids, the proteinaceous transport components, and membrane …

Reversible Heparin Molecules And Methods Of Making And Using The Same, Jian Liu, Yongmei Xu, Robert J. Linhardt, Edward Harris

Department of Biochemistry: Faculty Publications

Methods and systems for synthesizing heparin compounds are provided . The chemoenzymatic synthesis of structurally homogeneous low molecular weight heparins that have a reversible anticoagulant activity is provided . Also disclosed are heparin compounds having anticoagulant activity , including a binding affinity to antithrombin and an anti - Xa activity , but no detectable anti - lla activity . Additionally , provided are synthetic , low - molecular weight heparin com pounds with reversible anticoagulant activity , where the anticoagulant activity is reversible by protamine.

Intraperitoneal Nanotherapy For Metastatic Ovarian Cancer Based On Sirna-Mediated Suppression Of Dj-1 Protein Combined With A Low Dose Of Cisplatin, Canan Schumann, Stephanie Chan, Jess A. Miller, Yuliya Bortnyak, Katherine Carey, Alex Fedchyk, Leon Wong, Tetiana Korzun, Abraham S. Moses, Anna Lorenz, Delany Shea, Olena Taratula, Oleh Khalimonchuk, Oleh Taratula

Department of Biochemistry: Faculty Publications

Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy outperformed cisplatin alone by inhibiting tumor growth …

Influenza D Virus M2 Protein Exhibits Ion Channel Activity In Xenopus Laevis Oocytes, Evan Daniel Kesinger

School of Biological Sciences: Dissertations, Theses, and Student Research

The Influenza virus M2 ion channel has good potential as a target for antiviral drugs, as the channel is necessary for viral replication. M2 of Influenza A and B viruses has beenstudied extensively, and is understood to function as a proton channel. Antiviral drugs like amantadine and rimantadine have been used to block the function of Influenza A virus M2. Influenza C virus M2 has also been researched and is understood to act as a chloride ion channel. However, the M2 channel of Influenza D virus (DM2) has been studied very little, and the activity and mechanism of the channel …

Structural Determinants For The Interactions Of Chemically Modified Nucleic Acids With The Stabilin‑2 Clearance Receptor, Hans Gaus, Colton M. Miller, Punit P. Seth, Edward N. Harris

Department of Biochemistry: Faculty Publications

The Stabilin receptors are systemic clearance receptors for some classes of chemically modified nucleic acid therapeutics. In this study, the recombinant human secreted ecto-domain of the small isoform of Stabilin-2 (s190) was purified from cell culture and evaluated for direct binding with a multitude of antisense oligonucleotides (ASOs) using a fluorescence polarizationbased assay. The tested ASOs varied in their backbone composition, modification of the ribose 2′ position, overall length of the oligo, and sequence of the nucleotide bases. A fully phosphorothioate (PS) ASO with a 5−10−5 pattern of flanking 2′-O-methoxyethyl modifications was then used to test the effects …

Characterization Of Metabolic Networks In Differentiated Cd4+ T Cells, Bailee Lichter

Honors Program: Senior Projects (Public)

CD4+ T cells play a critical role in the immune system and protecting the body from infection. Cell differentiation of T-cells leads to the specialization of the immune system and has been determined to have plasticity. Differentiation of the CD4+ T cells depends on cytokines present in the environment, concentration of antigens, types of antigen – presenting cells (APCs), and costimulatory molecules (Luckheeram, 2012). Commonly known differentiated T-cells include the T-helper 1 (Th1) and the T-helper 2 (Th2) cells. Upon CD4+ T cell activation, the cells undergo metabolic changes that allow for cell growth and division. By characterizing the metabolic …

Effects Of Lipid Activating Chemical Compounds On The Growth And Production Of Fatty Acids And Metabolites In Green Algae, David Nguyen, Nishikant Wase, Concetta Dirusso

UCARE: Research Products

This study examines the effects of small molecule lipid activating chemical compound, discovered from the high throughput screening (HTS) (2) methods of previous FATTT Lab studies on the growth and production of lipids and metabolites in microalgae. For this study, the effects of two lipid inducing chemical compounds from the HTS method were implemented with the microalgae strain Chlamydomonas reinhardtii CC-125. This experiment focused on scaling up to large amounts of culture, approximately 1L. These cultures were grown in specially designed large bioreactors that were able to accommodate for such large volume of algal culture. Algal cells were treated with …

Characterization Of Metabolic Network In T-Helper 2 Cells, Bailee Lichter

UCARE: Research Products

T-helper 2 (Th2) cells function in the adaptive immune system to coordinate responses to large extracellular pathogens (Luckheerham, 2012). Th2 cells are one of the differentiated subtypes cells of CD4+ T cells. CD4+ T cells recognize foreign pathogens and differenitated in specialized subtypes to affectively destroy the pathogen (Luckheerham, 2012). Upon CD4+ T cell activation, the cells undergo metabolic reprogaming, resulting in a shift in metabolism (Almedia, 2016).

We have successfully created a Th2 metabolic network model. The Th2 metabolic network model contains 1151 genes, 2601 metabolites, and 4654 reactions.

Photosystem Ii Subunit S Overexpression Increases The Efficiency Of Water Use In A Field-Grown Crop, Katarzyna Glowacka, Johannes Kromdijk, Katherine Kucera, Jiayang Xie, Amanda P. Cavanagh, Lauriebeth Leonelli, Andrew D. B. Leakey, Donald R. Ort, Krishna K. Niyogi, Stephen P. Long

Department of Biochemistry: Faculty Publications

Insufficient water availability for crop production is a mounting barrier to achieving the 70% increase in food production that will be needed by 2050. One solution is to develop crops that require less water per unit mass of production. Water vapor transpires from leaves through stomata, which also facilitate the influx of CO2 during photosynthetic assimilation. Here, we hypothesize that Photosystem II Subunit S (PsbS) expression affects a chloroplastderived signal for stomatal opening in response to light, which can be used to improve wateruse efficiency. Transgenic tobacco plants with a range of PsbS expression, from undetectable to 3.7 …

Simulation Of Stimulation: Cytokine Dosage And Cell Cycle Crosstalk Driving Timing-Dependent T Cell Differentiation, Matteo Barberis, Tomáš Helikar, Paul Verbruggen

Department of Biochemistry: Faculty Publications

Triggering an appropriate protective response against invading agents is crucial to the effectiveness of human innate and adaptive immunity. Pathogen recognition and elimination requires integration of a myriad of signals from many different immune cells. For example, T cell functioning is not qualitatively, but quantitatively determined by cellular and humoral signals. Tipping the balance of signals, such that one of these is favored or gains advantage on another one, may impact the plasticity of T cells. This may lead to switching their phenotypes and, ultimately, modulating the balance between proliferating and memory T cells to sustain an appropriate immune response. …

Computational Systems Biology Approach For The Study Of Rheumatoid Arthritis: From A Molecular Map To A Dynamical Model, Vidisha Singh, Marek Ostaszewski, George D. Kalliolias, Gilles Chiocchia, Robert Olaso, Elisabeth Petit-Teixeira, Tomáš Helikar, Anna Niarakis

Department of Biochemistry: Faculty Publications

In this work we present a systematic effort to summarize current biological pathway knowledge concerning Rheumatoid Arthritis (RA). We are constructing a detailed molecular map based on exhaustive literature scanning, strict curation criteria, re-evaluation of previously published attempts and most importantly experts’ advice. The RA map will be web-published in the coming months in the form of an interactive map, using the MINERVA platform, allowing for easy access, navigation and search of all molecular pathways implicated in RA, serving thus, as an on line knowledgebase for the disease. Moreover the map could be used as a template for Omics data …

The Colomoto Interactive Notebook: Accessible And Reproducible Computational Analyses For Qualitative Biological Networks, Aurelien Naldi, Celine Hernandez, Nicolas Levy, Gautier Stoll, Pedro T. Monteiro, Claudine Chaouiya, Tomáš Helikar, Andrei Zinovyev, Laurence Calzone, Sarah Cohen-Boulakia, Denis Thieffry, Loic Pauleve

Department of Biochemistry: Faculty Publications

Analysing models of biological networks typically relies on workflows in which different software tools with sensitive parameters are chained together,many times with additional manual steps. The accessibility and reproducibility of such workflows is challenging, as publications often overlook analysis details, and because some of these tools may be difficult to install, and/or have a steep learning curve. The CoLoMoTo Interactive Notebook provides a unified environment to edit, execute, share, and reproduce analyses of qualitative models of biological networks. This framework combines the power of different technologies to ensure repeatability and to reduce users’ learning curve of these technologies. The framework …

A Mechanistic Computational Model Reveals That Plasticity Of Cd4+ T Cell Differentiation Is A Function Of Cytokine Composition And Dosage, Bhanwar Lal Puniya, Robert G. Todd, Akram Mohammed, Deborah M. Brown, Matteo Barberis, Tomáš Helikar

Department of Biochemistry: Faculty Publications

CD4+ T cells provide cell-mediated immunity in response to various antigens. During an immune response, naïve CD4+ T cells differentiate into specialized effector T helper (Th1, Th2, and Th17) cells and induced regulatory (iTreg) cells based on a cytokine milieu. In recent studies, complex phenotypes resembling more than one classical T cell lineage have been experimentally observed. Herein, we sought to characterize the capacity of T cell differentiation in response to the complex extracellular environment. We constructed a comprehensive mechanistic (logical) computational model of the signal transduction that regulates T cell differentiation. The model’s dynamics were characterized and analyzed under …