Microbiology Commons^™

The ‘Law Of Environmental Dependence’ - Biology And Ethics In The Work Of Ernest Everett Just: + Found – Some 251 Mostly Typed Pages, Theodore Walker

Perkins Faculty Research and Special Events

Abstract-

“The Origin of Man’s Ethical Behavior” (circa October 1941) by Ernest Everett Just and Hedwig A. Schnetzler Just - is an unpublished book manuscript about the biological origins and evolution of ethical behavior, and about “the law of environmental dependence.” Missing since Just’s death in October 1941, it was found and identified in May 2018 among the collected papers of Ernest Everett Just preserved at the Howard University Moorland-Spingarn Research Center in Washington, DC. In addition to the 1996 US postage with the caption “Ernest E. Just, Biologist,” we now have reason to add two new postage stamps with …

Development Of A Prolyl Endopeptidase Expression System In Lactobacillus Reuteri To Reduce The Clinical Manifestation Of Celiac Disease, Kara Lynn Jew

Master's Theses

Celiac Disease (CD) is an autoimmune disorder that emerges due to the ingestion of gluten, a protein found in a variety of common grains such as wheat, rye, and barley. Approximately 1 in 100 individuals in the US suffer from CD, making it the most commonly diagnosed gastrointestinal disorder (Ciclitira et. al., 2005). These proline-rich gluten peptides are resistant to proteolysis and accumulate in the duodenum of the small intestine. Once in the duodenum, these peptides illicit an autoimmune response resulting in villous atrophy. Current treatment for CD requires a rigorous adherence to a gluten-free diet. Nevertheless, gluten-containing grains are …

The Effect Of Intracellular Zinc Levels In Escherichia Coli On Metallo-Β-Lactamase Activity, Jill Thompson

Graduate School of Biomedical Sciences Theses and Dissertations

Antibiotic resistance is a consequence of evolution via natural selection and poses a serious threat to the world's population. Escherichia coli, and other bacterial species, have acquired genes encoding Metallo-β-Lactamases (MBLs). MBLs are zinc-dependent enzymes that degrade most β-lactam antibiotics, and have emerged as important antibacterial resistance determinants in multidrug resistant pathogens. There are several different families of MBLs, and the major clinically relevant ones are Verona Integrated-encoded Metallo-β-Lactamases (VIMs), Imipenemases (IMPs), and New Delhi Metallo-β-Lactamases (NDMs). These enzymes confer high level resistance to penicillins, cephalosporins, and carbapenems, and are not inhibited by FDA-approved β-lactamase inhibitors. Variants of NDM have …

Hippo Signaling In Cancer: Lessons From Drosophila Models, Kirti Snigdha, Karishma Sanjay Gangwani, Gauri Vijay Lapalikar, Amit Singh, Madhuri Kango-Singh

Biology Faculty Publications

Hippo pathway was initially identified through genetic screens for genes regulating organ size in fruitflies. Recent studies have highlighted the role of Hippo signaling as a key regulator of homeostasis, and in tumorigenesis. Hippo pathway is comprised of genes that act as tumor suppressor genes like hippo (hpo) and warts (wts), and oncogenes like yorkie (yki). YAP and TAZ are two related mammalian homologs of Drosophila Yki that act as effectors of the Hippo pathway. Hippo signaling deficiency can cause YAP- or TAZ-dependent oncogene addiction for cancer cells. YAP and TAZ are often activated …

Kinetics Of Hiv-1 Uncoating In C20 Microglial Cells, Melanie Anne Taylor

Graduate Theses/Dissertations

Uncoating is a poorly understood yet required step of HIV-1 replication that is defined as the disassembly of the viral capsid structure. The goal of this project is to characterize uncoating in C20 microglial cells. These cells are a natural target of HIV-1 that are infected to establish latent viral reservoirs and HIV-associated neurological disorders. A stable C20 cell line that expresses TRIM-CypA was established to study the kinetics of uncoating with the CsA washout assay. The expression of TRIM-CypA was confirmed by western blot and the functionality of the protein was confirmed by a viral infectivity assay. Using this …

Yfmk Is A Novel Nε-Lysine Acetyltransferase That Directly Acetylates The Histone-Like Protein Hbsu In Bacillus Subtilis, Valerie J. Carabetta, Todd M. Greco, Ileana M. Cristea, David Dubnau

Rowan-Virtua Research Day

Recently, N^e-lysine acetylation was realized to be a prevalent bacterial post-translational modification (PTM), contrary to the historical notion that this was a rare occurrence. Acetylation can impact protein function in multiple ways, by modifying conformation, interactions, subcellular localization or activity. In bacteria, hundreds of proteins are known to be acetylated, including those involved essential processes such as DNA replication, nucleoid organization, translation, cell shape, central carbon metabolism, and even several virulence factors. Despite the growing recognition that numerous proteins are acetylated, the biological significance of the vast majority of these modifications in any bacteria remains largely unknown. Previously, …

Developing A Modern Microbiology Laboratory Manual To Enhance Student Learning, Alexander Yonchak

Senior Honors Projects

My project has been addressing the issue of incorporating recent developments in biosafety and pedagogical approaches for lab-courses into our existing educational curriculum by developing a new, modern lab manual aimed at improving experiential learning for introductory microbiology teaching labs. Through researching the most recent safety regulations, industry standards, & guidelines for such teaching labs, my manual clearly delineates learning outcomes to match the skills expected of undergraduates completing degrees within the life sciences. In addition, the lab manual that I have designed has been modernized to incorporate the most recent recommended safety precautions and is written in a user-friendly …

Thiol-Based Misfolding: Linking Redox Balance To Cytosolic Proteostasis, Ford Amy

Dissertations and Theses (Open Access)

The eukaryotic cytosolic proteome is vulnerable to changes in proteostatic and redox balance caused by temperature, pH, oxidants and xenobiotics. Cysteine-containing proteins are especially at risk as the thiol side chain is subject to oxidation, adduction and chelation by thiol-reactive compounds. All of these thiol-modifiers have been demonstrated to induce the heat shock response and recruit protein chaperones to sites of presumed protein aggregation in the budding yeast Saccharomyces cerevisiae. However, endogenous targets of thiol stress toxicity responsible for these outcomes are largely unknown. Furthermore, I hypothesize proteins identified as redox-active are prone to misfolding and aggregation by thiol-specific …

Characterization Of Microtubule Organizing Centers In The Genus Protostelium, Including Evolutionary Implications, Ethan Taylor Ozment

Graduate Theses and Dissertations

Microtubule organizing centers (MTOCs) are cellular regions of microtubule nucleation. The best known MTOCs are those associated with the centrosome, but several non-centrosomal MTOCs are known in eukaryotes, especially in land plants. MTOCs are poorly characterized across the breadth of amoebozoan diversity, but are well-known in certain amoebozoan lineages, including the genus of protosteloid slime molds Protostelium. The structure of the MTOC is known for two non-ciliated species, P. nocturnum and P. mycophaga, as well as P. aurantium, which can reversibly become ciliated under appropriate conditions. P. nocturnum and P. mycophaga have acentriolar centrosomal MTOCs while P. aurantium has a …

Combating Drug Resistance - Comparison Of The Antibiotic Effect Of Hydrastis Canadensis Extract And Pure Berberine Via Minimum Inhibitory Concentration Assay, William Luke Scott, Timothy D. Trott

Research in Biology

Herbal medicines are a melee of complex organic chemicals, making it difficult to ascertain their direct mechanism of action. In contrast to mainstream pharmaceuticals, it is argued that herbal medicines are effective because of multiple constituents working synergistically. The complexity of herbal medicines may give them advantages over simpler pharmaceuticals in combating antibiotic resistant microbes, but these advantages can be difficult to quantitate. Popular literature frequently espouses the healing properties of herbal medicines, but many of these claims are not scientifically supported. Many gains could be realized in public health and medicine if more research was aimed at validating / …

Streptococcus Agalactiae Strains With Chromosomal Deletions Evade Detection With Molecular Methods, Isabella A. Tickler, Fred C. Tenover, Scott Dewell, Victoria M. Le, Rachel N. Blackman, Richard V. Goering, Amy E. Rogers, Heather Piwonka, Brittney D. Jung-Hynes, Derrick J. Chen, Michael J. Loeffelholz, Devasena Gnanashanmugam, Ellen Jo Baron

Biology Faculty Publications

Surveillance of circulating microbial populations is critical for monitoring the performance of a molecular diagnostic test. In this study, we characterized 31 isolates of Streptococcus agalactiae (group B Streptococcus [GBS]) from several geographic locations in the United States and Ireland that contain deletions in or adjacent to the region of the chromosome that encodes the hemolysin gene cfb, the region targeted by the Xpert GBS and GBS LB assays. PCR-negative, culture-positive isolates were recognized during verification studies of the Xpert GBS assay in 12 laboratories between 2012 and 2018. Whole-genome sequencing of 15 GBS isolates from 11 laboratories revealed …

Diversity Of Resistance Mechanisms In Carbapenem-Resistant Enterobacteriaceae At A Health Care System In Northern California, From 2013 To 2016, Fiona Senchyna, Rajiv L. Gaur, Johanna Sandlund, Cynthia Truong, Guillaume Tremintin, Dietmar Kültz, Carlos A. Gomez, Fiona B. Tamburini, Tessa Andermann, Ami Bhatt, Isabella A. Tickler, Nancy Watz, Indre Budvytiene, Gongyi Shi, Fred C. Tenover, Niaz Banaei

Biology Faculty Publications

The mechanism of resistance in carbapenem-resistant Enterobacteriaceae (CRE) has therapeutic implications. We comprehensively characterized emerging mechanisms of resistance in CRE between 2013 and 2016 at a health system in Northern California. A total of 38.7% (24/62) of CRE isolates were carbapenemase gene-positive, comprising 25.0% (6/24) blaOXA-48 like, 20.8% (5/24) bla_KPC, 20.8% (5/24) bla_NDM, 20.8% (5/24) bla_SME, 8.3% (2/24) bla_IMP, and 4.2% (1/24) bla_VIM. Between carbapenemases and porin loss, the resistance mechanism was identified in 95.2% (59/62) of CRE isolates. Isolates expressing bla_KPC were 100% susceptible to ceftazidime–avibactam, meropenem–vaborbactam, …

Enhancement Of Immune Response Against Bordetella Spp. By Disrupting Immunomodulation, Monica C. Gestal, Laura K. Howard, Kalyan Dewan, Hannah M. Johnson, Mariette Barbier, Clare Bryant, Illiassou Hamidou Soumana, Israel Rivera, Bodo Lina, Uriel Blas-Machado, Eric T. Harvill

Faculty & Staff Scholarship

Well-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway. The deletion of btrS in B. bronchiseptica did not affect colonization or initial growth in the …

Cornus Officinalis Significantly Improves Oxidative Capacity And Promotes The Calcium-Dependent Transcription Factor, Nfatc2, In Human 1.1b4 Pancreatic Cell Line, Arielle Sharp, Alexis Coiner, Brant Burkhardt

Molecular Biosciences Faculty Publications

Type 1 diabetes (T1D) is an autoimmune disease resulting in the destruction of pancreatic β cells (β-cells) and subsequent loss of insulin production. The only treatment for T1D is using exogenous insulin coupled with continual glucose monitoring following significant autoimmune destruction of β-cells. Novel interventional therapies are needed that can preserve and protect existing pancreatic β cells in individuals with early identified T1D autoimmunity. Our initial in-vitro evidence indicates Cornus officinalis (CO) may be able to serve in this function. What sets ethnopharmacology apart from conventional medicine is the simultaneous targeting of multiple mechanisms using a single herb due to …

Structural Basis Of Phosphatidylcholine Recognition By The C2–Domain Of Cytosolic Phospholipase A,2Α, Yoshinori Hirano, Yong-Guang Gao, Daniel J. Stephenson, Ngoc T. Vu, Lucy Malinina, Dhirendra K. Simanshu, Charles E. Chalfant, Dinshaw J. Patel, Rhoderick E. Brown

Molecular Biosciences Faculty Publications

Ca²⁺-stimulated translocation of cytosolic phospholipase A2α (cPLA2α) to the Golgi induces arachidonic acid production, the rate-limiting step in pro-inflammatory eicosanoid synthesis. Structural insights into the cPLA2α preference for phosphatidylcholine (PC)-enriched membranes have remained elusive. Here, we report the structure of the cPLA2α C2-domain (at 2.2 Å resolution), which contains bound 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) and Ca2+ ions. Two Ca2+ are complexed at previously reported locations in the lipid-free C2-domain. One of these Ca2+ions, along with a third Ca2+, bridges the C2-domain to the DHPC phosphate group, which also interacts with Asn65. Tyr96 plays a key role in lipid …

Conserved Glycines Control Disorder And Function In The Cold-Regulated Protein, Cor15a, Oluwakemi T. Sowemimo, Patrick Knox-Brown, Wade M. Borcherds, Tobias Rindfleisch, Anja Thalhammer, Gary W. Daughdrill

Molecular Biosciences Faculty Publications

Cold-regulated (COR) 15A is an intrinsically disordered protein (IDP) from Arabidopsis thaliana important for freezing tolerance. During freezing-induced cellular dehydration, COR15A transitions from a disordered to mostly α-helical structure. We tested whether mutations that increase the helicity of COR15A also increase its protective function. Conserved glycine residues were identified and mutated to alanine. Nuclear magnetic resonance (NMR) spectroscopy was used to identify residue-specific changes in helicity for wildtype (WT) COR15A and the mutants. Circular dichroism (CD) spectroscopy was used to monitor the coil–helix transition in response to increasing concentrations of trifluoroethanol (TFE) and ethylene glycol. The impact of the COR15A …

Functional Inhibition Of Acid Sphingomyelinase Disrupts Infection By Intracellular Bacterial Pathogens, Chelsea L. Cockburn, Ryan S. Green, Sheela R. Damle, Rebecca K. Martin, Naomi N. Ghahrai, Punsiri M. Colonne, Marissa S. Fullerton, Daniel H. Conrad, Charles E. Chalfant, Daniel E. Voth, Elizabeth A. Rucks, Stacey D. Gilk, Jason A. Carlyon

Molecular Biosciences Faculty Publications

Intracellular bacteria that live in host cell–derived vacuoles are significant causes of human disease. Parasitism of low-density lipoprotein (LDL) cholesterol is essential for many vacuole-adapted bacteria. Acid sphingomyelinase (ASM) influences LDL cholesterol egress from the lysosome. Using functional inhibitors of ASM (FIASMAs), we show that ASM activity is key for infection cycles of vacuole-adapted bacteria that target cholesterol trafficking—Anaplasma phagocytophilum, Coxiella burnetii, Chlamydia trachomatis, and Chlamydia pneumoniae. Vacuole maturation, replication, and infectious progeny generation by A. phagocytophilum, which exclusively hijacks LDL cholesterol, are halted and C. burnetii, for which lysosomal cholesterol accumulation is bactericidal, …

Functional Analysis Of The Replication Fork Proteome Identifies Bet Proteins As Pcna Regulators, Sarah R. Wessel, Kareem N. Mohni, Jessica W. Luzwick, Huzefa Dungrawala, David Cortez

Molecular Biosciences Faculty Publications

Identifying proteins that function at replication forks is essential to understanding DNA replication, chromatin assembly, and replication-coupled DNA repair mechanisms. Combining quantitative mass spectrometry in multiple cell types with stringent statistical cutoffs, we generated a high-confidence catalog of 593 proteins that are enriched at replication forks and nascent chromatin. Loss-of-function genetic analyses indicate that 85% yield phenotypes that are consistent with activities in DNA and chromatin replication or already have described functions in these processes. We illustrate the value of this resource by identifying activities of the BET family proteins BRD2, BRD3, and BRD4 in controlling DNA replication. These proteins …

P53 Phosphomimetics Preserve Transient Secondary Structure But Reduce Binding To Mdm2 And Mdmx, Robin Levy, Emily Gregory, Wade Borcherds, Gary W. Daughdrill

Molecular Biosciences Faculty Publications

The disordered p53 transactivation domain (p53TAD) contains specific levels of transient helical secondary structure that are necessary for its binding to the negative regulators, mouse double minute 2 (Mdm2) and MdmX. The interactions of p53 with Mdm2 and MdmX are also modulated by posttranslational modifications (PTMs) of p53TAD including phosphorylation at S15, T18 and S20 that inhibits p53-Mdm2 binding. It is unclear whether the levels of transient secondary structure in p53TAD are changed by phosphorylation or other PTMs. We used phosphomimetic mutants to determine if adding a negative charge at positions 15 and 18 has any effect on the transient …

The Otud5–Ubr5 Complex Regulates Fact-Mediated Transcription At Damaged Chromatin, Angelo De Vivo, University Of South Florida, Jose Yegres, Jeonghyeon Kim, Sylvia Emly, Younghoon Kee

Molecular Biosciences Faculty Publications

Timely stalling and resumption of RNA polymerases at damaged chromatin are actively regulated processes. Prior work showed an importance of FACT histone chaperone in such process. Here we provide a new role of OTUD5 deubiquitinase in the FACT-dependent process. Through a DUB RNAi screen, we found OTUD5 as a specific stabilizer of the UBR5 E3 ligase. OTUD5 localizes to DNA double strand breaks (DSBs), interacts with UBR5 and represses the RNA Pol II elongation and RNA synthesis. OTUD5 co-localizes and interacts with the FACT component SPT16 and antagonizes the histone H2A deposition at DSB lesions. OTUD5 interacts with UBR5 and …

Genome Sequences Of Three Cruciviruses Found In The Willamette Valley (Oregon), Ignacio De La Higuera, Ellis L. Torrance, Alyssa A. Pratt, George Kasun, Amberlee Maluenda, Kenneth M. Stedman

Biology Faculty Publications and Presentations

Cruciviruses are single-stranded DNA (ssDNA) viruses whose genomes suggest the possibility of gene transfer between DNA and RNA viruses. Many crucivirus genome sequences have been found in metagenomic data sets, although no crucivirus has been isolated. Here, we present the complete genome sequences of three cruciviruses recovered from environmental samples from Oregon.

Monocytes And Monocyte-Derived Antigen-Presenting Cells Have Distinct Gene Signatures In Experimental Model Of Multiple Sclerosis, Kelly L. Monaghan, Wen Zheng, Gangqing Hu, Edwin C. K. Wan

Faculty & Staff Scholarship

Multiple sclerosis (MS) is a chronic inflammatory disease mediated by a complex interaction between the autoreactive lymphocytes and the effector myeloid cells within the central nervous system (CNS). In a murine model of MS, experimental autoimmune encephalomyelitis (EAE), Ly6Chi monocytes migrate into the CNS and further differentiate into antigen-presenting cells (APCs) during disease progression. Currently, there is no information about gene signatures that can distinguish between monocytes and the monocyte-derived APCs. We developed a surface marker-based strategy to distinguish between these two cell types during the stage of EAE when the clinical symptoms were most severe, and performed transcriptome analysis …

Exploring The Efficacy Of Natural Products In Alleviating Alzheimer’S Disease Using Animal Models, Prajakta Deshpande, Neha Gogia, Amit Singh

Biology Faculty Publications

Alzheimer’s disease (hereafter AD) is a progressive neurodegenerative disorder that affects the central nervous system. There are multiple factors that cause AD, viz., accumulation of extracellular Amyloid-beta 42 plaques, intracellular hyper-phosphorylated Tau tangles, generation of reactive oxygen species due to mitochondrial dysfunction and genetic mutations. The plaques and tau tangles trigger aberrant signaling, which eventually cause cell death of the neurons. As a result, there is shrinkage of brain, cognitive defects, behavioral and psychological problems. To date, there is no direct cure for AD. Thus, scientists have been testing various strategies like screening for the small inhibitor molecule library …

Xylan Metabolism By Caulobacter Crescentus, Viet Bui

Masters Theses

Bacteria present unique opportunities to explore the molecular mechanisms of nutrient acquisition processes at single cell level under various experimental conditions. Caulobacter crescentus is a gram-negative oligotrophic environmental bacterium with adaptive physiological responses, such as slow growth or complete arrest of cell cycle, presence of sessile and motile progenies with the sessile cells growing stalk to enhance nutrient uptake for growth in low-nutrient conditions. Details of plant polysaccharide-derived carbon compound, such as cellobiose, maltose, and xylose utilization by C. crescentus can be found but molecular details or mechanisms of polysaccharide utilization, such as xylan, has not been reported. Database analyses …

Illumination Of The Golgi Apparatus Of Pathogenic And Nonpathogenic Naegleria Species, Tyler M. Poe

Theses and Dissertations

In this study, Naegleria fowleri, a pathogenic amoeba and the causative agent of Primary Amebic Meningoencephalitis (PAM), was utilized to determine the presence or absence of classically conserved Golgi molecules featured in the expression of a Golgi apparatus. Previous studies concluded no Golgi expression via light microscopy and transmission electron microscopy, but a recent report on Naegleria gruberi indicated the presence of dispersed Golgi tubules. Non-pathogenic species of the Naegleria genus such as Naegleria gruberi 30540 and Naegleria lovaniensis 30569 were utilized in Western immunoblot analysis compared to reduced whole-cell lysate proteins of two strains of N. fowleri and …

Investigating The Impact Of Oxidative Stress On Tetrahymena Thermophila Sirtuin,Thd 18, Emmanuel Dubuisson

Publications and Research

Sirtuins are a family of enzymes that fulfill various important biological functions. Investigators have looked for the implication of Sirtuin genes in cell signaling mechanisms, in the formation and silencing of heterochromatin, in the regulation of ion channels, and in the modulation of the cellular redox reactions[2]. Different model organisms have been previously used to conduct these studies; among them, there are yeasts, nematodes, and fruit flies. Each one has made some valuable contribution into the vast body of knowledge related to this field.

However, gaps in the understanding of Sirtuins functions still remain to be filled. In this optic, …

Engineering Yeast To Evaluate Human Proteins Involved In Selective Rna Packaging During Hiv Particle Production, Ryan M. Bitter

Master's Theses

Despite recent advances in antiretroviral therapy, nearly 37 million people continue to live with human immunodeficiency virus (HIV). Basic and applied research on the assembly of HIV could be enhanced by using a genetically tractable organism, such as yeast, rather than mammalian cells. While previous studies showed that expression of the HIV Gag polyprotein in Saccharomyces cerevisiae spheroplasts resulted in the production of virus-like particles (VLPs), many questions regarding the utility of yeast in HIV assembly remain uninvestigated. Here, we report use of S. cerevisiae for both the production of VLPs with selectively packaged RNA and to evaluate the human …

Cysteine Residues Contribute To The Dimerization And Enzymatic Activity Of Human Nuclear Dutp Nucleotidohydrolase (Ndut)., Shawna M Rotoli, Julia L Jones, Salvatore J Caradonna

Rowan-Virtua School of Osteopathic Medicine Departmental Research

dUTPase is an enzyme found in all organisms that have thymine as a constituent of DNA. Through evolution, humans have two major isoforms of dUTPase: a mitochondrial (mDut) and a nuclear (nDut) isoform. The nuclear isoform of dUTPase is a 164-amino-acids-long protein containing three cysteine residues. nDut's starting methionine is post-translationally cleaved, leaving four unique amino acids on its amino-terminus including one cysteine residue (C3). These are not present in the mitochondrial isoform (mDut). Using mass spectrometry analyses of recombinant dUTPase constructs, we have discovered an intermolecular disulfide bridge between cysteine-3 of each nDut monomer. We have found that these …

Characterization Of The Protective Role Of Th17 Cells In An Fc Receptor-Targeted Vaccine Strategy Against Fracisella Tularensis Infection, Kyle Devenney

Seton Hall University Dissertations and Theses (ETDs)

Using a murine model, we have previously showed that targeting an inactivated form of F.tularensis (iFt) bacteria to Fcg receptors by utilizing an IgG2a, anti-LPS monoclonal antibody (mAb) provides 100% protection against a lethal dose with the live vaccine strain (LVS). The binding of anti-LPS monoclonal antibodies and iFt create an immune complex (mAb-iFt) allowing the Fc-region of the antibody to target Fc receptors expressed on antigen presenting cells, leading to a more robust and effective processing and presentation of the bacterial antigens. Although the resulting protective response generated relies on both humoral and cell-mediated immunity, in our study we …

Mechanisms Adopted By Dengue-2 Viruses To Induce Autophagy In Mammalian Cells, Sounak Ghosh Roy

Dissertations, Theses, and Capstone Projects

Dengue, the most rapidly spreading flavivirus, threatens to affect almost half of the human global population. We previously showed that dengue-2 protects canine kidney cells (MDCK) from cytotoxic chemicals. We showed, independently, that cell protection, as well as viral replication and maturation, are positively regulated by PI3K-dependent autophagy. However, we had not identified the specific pathway that induces autophagy in infected cells. The current study explores the role of a specific branch of the endoplasmic reticulum (ER) stress-mediated Unfolded Protein Response (UPR), the PERK/eIF2α/ATF4 pathway in the induction of autophagy by …