DOCSLIB.ORG

Award Winners and Abstracts of the 30Th Anniversary Symposium of the Protein Society, Baltimore, MD, July 16-19, 2016

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Award Winners and Abstracts of the 30Th Anniversary Symposium of the Protein Society, Baltimore, MD, July 16-19, 2016 Award Winners and Abstracts of the 30th Anniversary Symposium of The Protein Society, Baltimore, MD, July 16-19, 2016 4 ABSTRACT 2016 Award Winners BALTIMORE, MD – The Protein Society, the premiere international society dedicated to support- ing protein research, announces the winners of The 2016 Protein Society Awards. The awards were conferred at the 30th Anniversary Symposium of The Protein Society (July 16-19, 2016, Bal- timore, Maryland USA). Plenary talks from each recipient were scheduled throughout the 3.5 day event. The Carl Brand€ en Award The Carl Brand€ en Award, sponsored by Rigaku Corporation, honors an outstanding protein scientist who has also made exceptional contributions in the areas of education and/or service to the field. The 2016 recipient of this award is Dr. Gary Pielak (University of North Carolina at Chapel Hill). Dr. Pielak has advanced the field of protein chemistry through pioneering research in unraveling protein biophysics in living cells. Dr. Pielak and his students developed innovative quantitative techniques to measure protein stability and diffusion in crowded samples that interfere with standard measurement techniques. He has also made major advances in elucidating how the intracellular environment impacts both globular and intrinsically disordered proteins in surprising ways. Dr. Pielak has revolutionized our understanding of how proteins work where they actually function – inside cells – and not in the artificial environment of the test tube. The Dorothy Crowfoot Hodgkin Award The Dorothy Crowfoot Hodgkin Award, sponsored by Genentech, is granted in recognition of excep- tional contributions in protein science which profoundly influence our understanding of biology. The 2016 award will be presented to Dr. Rachel Klevit (University of Washington). Dr. Klevit’s research contri- butions have made a profound impact on the way we understand very important aspects of biological chemistry including how phosphorylation alters protein activity, regulation of transcription, and ubiqui- tylation. From the first structures of a zinc-finger and the RING E3 ubiquitin ligase BRCA1, Dr. Klevit has pushed NMR spectroscopy to establish new paradigms. Her research has been instrumental in under- standing the mechanism of disease of two scourges, breast cancer and Parkinson’s Disease. Moreover she has changed the way research in this area is done. Additionally, she is an exceptional mentor of younger scientists and wonderful role model for other scientists and educators at all stages of their careers. The Hans Neurath Award The Hans Neurath Award, sponsored by The Neurath Foundation, seeks to honor individuals who have made a recent contribution of exceptional merit to basic protein research. In 2016, the Hans Neurath winner is Dr. H. Eric Xu (Van Andel Research Institute). Dr. Xu established and served as the distin- guished Director of the VARI-SIMM Center for Drug Discovery at Shanghai Institute of Materia (SIMM) of Chinese Academy of Sciences. Research in his group has previously been supported by four NIH R01 grants, one Senior Investigator Award from American Asthma Foundation, and one past DOD prostate cancer idea development award, which cover structures and drug discovery of nuclear hormone recep- tors, hepatocyte growth factor and its receptor Met tyrosine kinase, G-protein coupled receptors, and plant hormones. Two of his research papers on plant hormones were selected as top 10 breakthroughs by Science in 2009 and by Chinese Academy of Sciences in 2014, and his recent X-ray laser structure of the first GPCR-arrestin complex was also selected as a top 10 breakthrough by Chinese Academy of Sci- ences in 2016. 5 ABSTRACT The Christian B. Anfinsen Award The Christian B. Anfinsen Award, sponsored by The Protein Society, recognizes technological achieve- ment or significant methodological advances in the field of protein science. The recipient of this award in 2016 is Dr. Andreas Pluckthun€ (University of Zurich). Dr. Pluckthun€ is a pioneer of protein engineer- ing. By combining rigorous biophysical studies with the invention of new combinatorial and evolution- ary technologies, he has advanced both basic and applied science. His research greatly contributed to enabling the emergence of antibody engineering, by the use of E. coli as an engineering platform and studies on synthetic antibodies which led to the first fully synthetic antibody library. To create a true in vitro protein evolution technology he developed ribosome display of whole proteins. Through his work, designed ankyrin repeat proteins (DARPins) were created as a robust alternative scaffold for binding proteins. Innovative directed evolution technologies have led to highly stable G protein-coupled recep- tors that can be used for structural studies and in drug screening. Several engineered therapeutics, developed on the basis of his research, are now in late phase clinical development. The Emil Thomas Kaiser Award The Emil Thomas Kaiser Award recognizes a recent, highly significant contribution to the application of chemistry in the study of proteins. The 2016 recipient is Dr. Charles S. Craik (University of California, San Francisco). Dr. Craik the founder and director of the Chemistry and Chemical Biology Graduate Program. He received his education and training at Allegheny College (BS), Columbia University (Ph.D.) and UCSF (Postdoctoral). He joined the UCSF faculty in 1985 where his research interests focus on defining the roles and the mechanisms of enzymes in complex biological processes and on developing technologies to facilitate these studies. He is also founder of Catalyst Biosciences, a biotechnology company focused on therapeutic proteases. Craik is a Fellow of the American Association for the Advancement of Science (AAAS) and the National Academy of Inventors (NAI). The current research in the Craik lab focuses on the chemical biology of proteolytic enzymes, their receptors and their natural inhibitors. A particular emphasis of his work is on identifying the roles and regulating the activity of proteases and degradative enzyme complexes associated with infectious diseases and cancer. These studies coupled with his global substrate profiling and noninvasive imaging efforts are providing a better understanding of both the chemical make-up and the biological importance of these critical proteins to aid in the rapid detection, monitoring and control of infectious disease and cancer. The Stein and Moore Award The Stein and Moore Award is named for Nobel laureates Dr. William Stein and Dr. Stanford Moore. The award venerates eminent leaders in protein science who have made sustained, high impact research contributions to the field. The 2016 recipient is Dr. Jane Clarke (University of Cambridge, UK). Dr. Clarke is Professor of Molecular Biophysics in the Chemistry Department of the University of Cambridge. Her research is multidisciplinary, combining single molecule and ensemble biophysical techniques with pro- tein engineering and simulations to investigate protein folding, misfolding and assembly. In her role as Deputy Head of the Chemistry Department in Cambridge, Dr. Clarke became involved in mentoring, career development, and leadership training for scientists at all stages in their careers. The Protein Science Young Investigator Award The Protein Science Young Investigator Award, named for the academic journal of the Society, Recog- nizes a scientist generally within the first 8 years of an independent career who has made an important contribution to the study of proteins. The 2016 winner is Dr. Benjamin Garcia (University of Pennsylvania Perelman School of Medicine). Dr. Garcia has been developing analytical and computational tools to 6 ABSTRACT understand the combinatorial complexity of simultaneously occurring histone modifications, identifying thousands of uniquely modified histone H3 forms, the significance of which is the focus of current research interest (e.g. combinatorial Histone Code). He also been involved in development of advanced mass spectrometry instrumental approaches using electron transfer dissociation and data-independent acquisition to increase the accuracy and precision for protein and proteome characterization. The Garcia lab has been developing and applying novel mass spectrometry based proteomic approaches for inter- rogating protein post-translational modifications (PTMs), especially those involved in epigenetic mecha- nisms such as histones, publishing over 170 publications. The 2016 Protein Science Best Paper Award At the beginning of each year, two “best papers” are selected from articles published in “Protein Scien- ce” during the preceding 12 months. A junior author (typically the first author) is designated as the award winner and invited to give a talk at the following Annual Protein Society Symposium. Tracy Clinton is an Air Force biochemist who earned her Ph.D. at the University of Utah through the Air Force graduate education civilian institute program. As Tracy puts it, “I am passionate about science and earning my Ph.D. was a wonderful way to further my scientific education while working in an area of biological relevance to my career. The research I had the privilege to take part in was both exciting and challenging and allowed me to bring many new skills and knowledge back to my professional life. I am very thankful for the opportunity to be a small part of the great things that Dr. Kay’s lab has and will continue to achieve.” Michael Thompson grew up in the San Fernando Valley
Load more

Recommended publications
  • Synthesis of Conformationally Constrained Glutamate Analogues and Their Preliminary Evaluation As Glutamate Transport Inhibitors
    University of Montana ScholarWorks at University of Montana Graduate Student Theses, Dissertations, & Professional Papers Graduate School 2002 Synthesis of conformationally constrained glutamate analogues and their preliminary evaluation as glutamate transport inhibitors Travis Taylor Denton The University of Montana Follow this and additional works at: https://scholarworks.umt.edu/etd Let us know how access to this document benefits ou.y Recommended Citation Denton, Travis Taylor, "Synthesis of conformationally constrained glutamate analogues and their preliminary evaluation as glutamate transport inhibitors" (2002). Graduate Student Theses, Dissertations, & Professional Papers. 9450. https://scholarworks.umt.edu/etd/9450 This Dissertation is brought to you for free and open access by the Graduate School at ScholarWorks at University of Montana. It has been accepted for inclusion in Graduate Student Theses, Dissertations, & Professional Papers by an authorized administrator of ScholarWorks at University of Montana. For more information, please contact [email protected]. INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion.
    [Show full text]
  • Targeting the LKB1 Tumor Suppressor
    Send Orders for Reprints to [email protected] 32 Current Drug Targets, 2014, 15, 32-52 Targeting the LKB1 Tumor Suppressor Rui-Xun Zhao and Zhi-Xiang Xu* Division of Hematology and Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: LKB1 (also known as serine-threonine kinase 11, STK11) is a tumor suppressor, which is mutated or deleted in Peutz-Jeghers syndrome (PJS) and in a variety of cancers. Physiologically, LKB1 possesses multiple cellular functions in the regulation of cell bioenergetics metabolism, cell cycle arrest, embryo development, cell polarity, and apoptosis. New studies demonstrated that LKB1 may also play a role in the maintenance of function and dynamics of hematopoietic stem cells. Over the past years, personalized therapy targeting specific genetic aberrations has attracted intense interests. Within this review, several agents with potential activity against aberrant LKB1 signaling have been discussed. Potential strate- gies and challenges in targeting LKB1 inactivation are also considered. Keywords: LKB1 (serine-threonine kinase 11, STK11), AMP-activated protein kinase (AMPK), tumor suppression, mutations, targeting therapeutics. INTRODUCTION THE BIOLOGICAL FUNCTIONS OF LKB1 The LKB1 gene, also known as serine-threonine kinase Cell Metabolism 11 (STK11), was first identified by Jun-ichi Nezu of Chugai About a decade ago, studies from three different groups Pharmaceuticals in 1996 in a screen aimed at identifying new established that LKB1 is the long-sought kinase that phos- kinases [1]. The human LKB1 gene has been mapped to phorylates AMPK [9-11]. AMPK is a heterotrimeric enzyme chromosome 19p13.3. The gene spans 23 kb and is com- complex consisting of a catalytic subunit and regulatory posed of nine coding exons and a noncoding exon [2].
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Poster Abstracts
    POSTER ABSTRACTS Society of Toxicology (MASOT) www.masot.org Fall 2015 Scientific Meeting October 13th, 2015 Abstract 01 Tracking Inflammatory Macrophage Accumulation in the Lung during Ozone- induced Lung Injury in Mice M Francis, M Mandal, C. Sun, H Choi, JD Laskin, DL Laskin Rutgers University, Piscataway, NJ Ozone induced lung injury is associated with an accumulation of pro- and antiinflammatory macrophages (MP) in the lung which have been implicated in tissue injury and repair. In these studies, we used in vivo tracking techniques to investigate the origin of cell. Initially we generated bone marrow (BM) chimeric mice by adoptive transfer of BM cells from GFP+ mice into irradiated C57BL/6 mice. After 4 weeks, mice were exposed to air or ozone (0.8 ppm, 3 h). Macrophages were isolated from lungs 24- 72 h later, stained with fluorescent labeled antibodies, and analyzed by flow cytometry. Approximately 98% of BM cells were found to be GFP+ while only 5% were GFP+ in control lungs. Ozone exposure resulted in a marked increase in infiltrating mature GFP+CD11b+F4/80+ MP into the lung. Two populations, Ly6CHi proinflammatory and Ly6CLo antiinflammatory were identified. Proinflammatory GFP+Ly6CHi MP increased rapidly after ozone and remained elevated, increases in antiinflammatory GFP+Ly6CLo were transient. To assess potential mechanisms mediating the accumulation of these MP subpopulations in the lung, we used mice lacking Ccr2, a chemokine receptor involved in proinflammatory MP trafficking. Loss of Ccr2 resulted in decreased numbers of infiltrating CD11b+ MP in the lung. This was due to a selective reduction in proinflammatory Ly6CHi MP.
    [Show full text]
  • Genomic Analysis of Family UBA6911 (Group 18 Acidobacteria)
    bioRxiv preprint doi: https://doi.org/10.1101/2021.04.09.439258; this version posted April 10, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 2 Genomic analysis of family UBA6911 (Group 18 3 Acidobacteria) expands the metabolic capacities of the 4 phylum and highlights adaptations to terrestrial habitats. 5 6 Archana Yadav1, Jenna C. Borrelli1, Mostafa S. Elshahed1, and Noha H. Youssef1* 7 8 1Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, 9 OK 10 *Correspondence: Noha H. Youssef: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2021.04.09.439258; this version posted April 10, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 11 Abstract 12 Approaches for recovering and analyzing genomes belonging to novel, hitherto unexplored 13 bacterial lineages have provided invaluable insights into the metabolic capabilities and 14 ecological roles of yet-uncultured taxa. The phylum Acidobacteria is one of the most prevalent 15 and ecologically successful lineages on earth yet, currently, multiple lineages within this phylum 16 remain unexplored. Here, we utilize genomes recovered from Zodletone spring, an anaerobic 17 sulfide and sulfur-rich spring in southwestern Oklahoma, as well as from multiple disparate soil 18 and non-soil habitats, to examine the metabolic capabilities and ecological role of members of 19 the family UBA6911 (group18) Acidobacteria.
    [Show full text]
  • MIAMI UNIVERSITY the Graduate School Certificate for Approving The
    MIAMI UNIVERSITY The Graduate School Certificate for Approving the Dissertation We hereby approve the Dissertation of Qiuyuan Huang Candidate for the Degree: Doctor of Philosophy _______________________________________ Hailiang Dong, Director ________________________________________ Yildirim Dilek, Reader ________________________________________ Jonathan Levy, Reader ______________________________________ Chuanlun Zhang, External examiner ______________________________________ Annette Bollmann, Graduate School Representative ABSTRACT GEOMICROBIAL INVESTIGATIONS ON EXTREME ENVIRONMENTS: LINKING GEOCHEMISTRY TO MICROBIAL ECOLOGY IN TERRESTRIAL HOT SPRINGS AND SALINE LAKES by Qiuyuan Huang Terrestrial hot springs and saline lakes represent two extreme environments for microbial life and constitute an important part of global ecosystems that affect the biogeochemical cycling of life-essential elements. Despite the advances in our understanding of microbial ecology in the past decade, important questions remain regarding the link between microbial diversity and geochemical factors under these extreme conditions. This dissertation first investigates a series of hot springs with wide ranges of temperature (26-92oC) and pH (3.72-8.2) from the Tibetan Plateau in China and the Philippines. Within each region, microbial diversity and geochemical conditions were studied using an integrated approach with 16S rRNA molecular phylogeny and a suite of geochemical analyses. In Tibetan springs, the microbial community was dominated by archaeal phylum Thaumarchaeota
    [Show full text]
  • A Kinase and Site-Specific Endoribonuclease
    Ire1P 25 3 Ire1p: A Kinase and Site-Specific Endoribonuclease Tania N. Gonzalez and Peter Walter 1. Introduction 1.1. Ire1p in the Unfolded Protein Response The lumen of the endoplasmic reticulum (ER) is a highly specialized compartment in eukaryotic cells. Here, secretory and most membrane proteins are folded, covalently modified, and oligomerized with the assistance of specialized ER resident proteins (1). Perturbation of the ER lumen interferes with the production of many essential cellular components and can thus be highly deleterious. Indeed, in humans, defects in protein folding in the ER can lead to devastating diseases, such as cystic fibrosis, alpha1-anti- trypsin deficiency, and osteogenesis imperfecta (2). One way in which cells cope with the accumulation of unfolded proteins in the ER is by activating the unfolded protein response (UPR), an ER-to-nucleus signal transduction pathway (3–5). In the yeast Sac- charomyces cerevisiae, Ire1p is an essential component of this pathway. Ire1p is a transmembrane protein localized to ER membranes. When Ire1p was ini- tially identified as a component of the UPR, it was thought to function primarily as a serine/threonine kinase because of its homology to other kinases and its demonstrated kinase activity (6–8). Subsequent studies revealed that Ire1p functions as a site-spe- cific endoribonuclease as well (9). Both the kinase and endoribonuclease activities map to the carboxy-terminal half of Ire1p. The amino-terminal portion of Ire1p lies in the ER lumen (6,7), where it senses increases in the concentration of misfolded pro- teins. Since the ER and nuclear membranes are continuous, the carboxy-terminal portion of Ire1p is predicted to be located in either the cytoplasm and/or nucleus, where it induces downstream events in the UPR pathway.
    [Show full text]
  • Supplementary Table 1. Genes Mapped in Core Cancer
    Supplementary Table 1. Genes mapped in core cancer pathways annotated by KEGG (Kyoto Encyclopedia of Genes and Genomes), MIPS (The Munich Information Center for Protein Sequences), BIOCARTA, PID (Pathway Interaction Database), and REACTOME databases. EP300,MAP2K1,APC,MAP3K7,ZFYVE9,TGFB2,TGFB1,CREBBP,MAP BIOCARTA TGFB PATHWAY K3,TAB1,SMAD3,SMAD4,TGFBR2,SKIL,TGFBR1,SMAD7,TGFB3,CD H1,SMAD2 TFDP1,NOG,TNF,GDF7,INHBB,INHBC,COMP,INHBA,THBS4,RHOA,C REBBP,ROCK1,ID1,ID2,RPS6KB1,RPS6KB2,CUL1,LOC728622,ID4,SM AD3,MAPK3,RBL2,SMAD4,RBL1,NODAL,SMAD1,MYC,SMAD2,MAP K1,SMURF2,SMURF1,EP300,BMP8A,GDF5,SKP1,CHRD,TGFB2,TGFB 1,IFNG,CDKN2B,PPP2CB,PPP2CA,PPP2R1A,ID3,SMAD5,RBX1,FST,PI KEGG TGF BETA SIGNALING PATHWAY TX2,PPP2R1B,TGFBR2,AMHR2,LTBP1,LEFTY1,AMH,TGFBR1,SMAD 9,LEFTY2,SMAD7,ROCK2,TGFB3,SMAD6,BMPR2,GDF6,BMPR1A,B MPR1B,ACVRL1,ACVR2B,ACVR2A,ACVR1,BMP4,E2F5,BMP2,ACVR 1C,E2F4,SP1,BMP7,BMP8B,ZFYVE9,BMP5,BMP6,ZFYVE16,THBS3,IN HBE,THBS2,DCN,THBS1, JUN,LRP5,LRP6,PPP3R2,SFRP2,SFRP1,PPP3CC,VANGL1,PPP3R1,FZD 1,FZD4,APC2,FZD6,FZD7,SENP2,FZD8,LEF1,CREBBP,FZD9,PRICKLE 1,CTBP2,ROCK1,CTBP1,WNT9B,WNT9A,CTNNBIP1,DAAM2,TBL1X R1,MMP7,CER1,MAP3K7,VANGL2,WNT2B,WNT11,WNT10B,DKK2,L OC728622,CHP2,AXIN1,AXIN2,DKK4,NFAT5,MYC,SOX17,CSNK2A1, CSNK2A2,NFATC4,CSNK1A1,NFATC3,CSNK1E,BTRC,PRKX,SKP1,FB XW11,RBX1,CSNK2B,SIAH1,TBL1Y,WNT5B,CCND1,CAMK2A,NLK, CAMK2B,CAMK2D,CAMK2G,PRKACA,APC,PRKACB,PRKACG,WNT 16,DAAM1,CHD8,FRAT1,CACYBP,CCND2,NFATC2,NFATC1,CCND3,P KEGG WNT SIGNALING PATHWAY LCB2,PLCB1,CSNK1A1L,PRKCB,PLCB3,PRKCA,PLCB4,WIF1,PRICK LE2,PORCN,RHOA,FRAT2,PRKCG,MAPK9,MAPK10,WNT3A,DVL3,R
    [Show full text]
  • The Microbiota-Produced N-Formyl Peptide Fmlf Promotes Obesity-Induced Glucose
    Page 1 of 230 Diabetes Title: The microbiota-produced N-formyl peptide fMLF promotes obesity-induced glucose intolerance Joshua Wollam1, Matthew Riopel1, Yong-Jiang Xu1,2, Andrew M. F. Johnson1, Jachelle M. Ofrecio1, Wei Ying1, Dalila El Ouarrat1, Luisa S. Chan3, Andrew W. Han3, Nadir A. Mahmood3, Caitlin N. Ryan3, Yun Sok Lee1, Jeramie D. Watrous1,2, Mahendra D. Chordia4, Dongfeng Pan4, Mohit Jain1,2, Jerrold M. Olefsky1 * Affiliations: 1 Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California, USA. 2 Department of Pharmacology, University of California, San Diego, La Jolla, California, USA. 3 Second Genome, Inc., South San Francisco, California, USA. 4 Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA. * Correspondence to: 858-534-2230, [email protected] Word Count: 4749 Figures: 6 Supplemental Figures: 11 Supplemental Tables: 5 1 Diabetes Publish Ahead of Print, published online April 22, 2019 Diabetes Page 2 of 230 ABSTRACT The composition of the gastrointestinal (GI) microbiota and associated metabolites changes dramatically with diet and the development of obesity. Although many correlations have been described, specific mechanistic links between these changes and glucose homeostasis remain to be defined. Here we show that blood and intestinal levels of the microbiota-produced N-formyl peptide, formyl-methionyl-leucyl-phenylalanine (fMLF), are elevated in high fat diet (HFD)- induced obese mice. Genetic or pharmacological inhibition of the N-formyl peptide receptor Fpr1 leads to increased insulin levels and improved glucose tolerance, dependent upon glucagon- like peptide-1 (GLP-1). Obese Fpr1-knockout (Fpr1-KO) mice also display an altered microbiome, exemplifying the dynamic relationship between host metabolism and microbiota.
    [Show full text]
  • Microglial Glutathione and Glutamate: Regulation Mechanisms
    Microglial glutathione and glutamate: Regulation mechanisms Victoria Anne Honey Fry UCL Institute of Neurology A thesis submitted for the degree of Doctor of Philosophy (Ph.D.) 1 I, Victoria Fry, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 2 Abstract Microglia, the immune cells of the central nervous system (CNS), are important in the protection of the CNS, but may be implicated in the pathogenesis of neuroinflammatory disease. Upon activation, microglia produce reactive oxygen and nitrogen species; intracellular antioxidants are therefore likely to be important in their self-defence. Here, it was confirmed that cultured microglia contain high levels of glutathione, the predominant intracellular antioxidant in mammalian cells. The activation of microglia with lipopolysaccharide (LPS) or LPS + interferon- was shown to affect their glutathione levels. GSH levels in primary microglia and those of the BV-2 cell line increased upon activation, whilst levels in N9 microglial cells decreased. - Microglial glutathione synthesis is dependent upon cystine uptake via the xc transporter, which exchanges cystine and glutamate. Glutamate is an excitatory neurotransmitter whose extracellular concentration is tightly regulated by excitatory amino acid transporters, as high levels cause toxicity to neurones and other CNS cell types through overstimulation of - glutamate receptors or by causing reversal of xc transporters. Following exposure to LPS, increased extracellular glutamate and increased levels of messenger ribonucleic acid - (mRNA) for xCT, the specific subunit of xc , were observed in BV-2 and primary microglial cells, suggesting upregulated GSH synthesis.
    [Show full text]
  • Extremophiles 90C
    Limits of Life on Earth Archaea and bacteria can thrive in extreme environment (heat, cold, acidity, high pressure) and can use unusual energy source Distinguish between growth and survival (e.g., seeds, spores) Analogs for extraterrestrial environments Origin of life in extreme environments? Origin of Yellowstone National Park pH scale pH 3 Temperature 60 C Rich in sulfur Nymph Creek Hydrogenobacter gets energy by reacting oxygen from the air with hydrogen gas and/or sulfide in the water. It uses the energy to make carbohydrate (sugar) from atmospheric carbon dioxide and hydrogen in the water: CO2 + 2 H2 = CH2O + H2O (where CH2O is part of a carbohydrate). Nymph Creek flowing into Nymph Lake, Yellowstone National Park; green mat of Cyanidium (pH 3, 40 to 45oC) Nymph Lake Hydrogenobacter acidocaldarius Hyperthermophile (T > 80 C), pH ≈ 3 H2 metabolism, low nutrient tolerant Hot springs in YNP, New Zealand & Australia + oil wells “Boiling Lake” Grand Prismatic 70 C Filled with thermophiles Sulphobus: optimum T~80C Orange “mats” of pigmented Minimum 60 C, maaximum extremophiles 90C. Lives by oxidizing sulfur (carotenoids) which is abundant near hot springs Adaptations of Thermophilies Similar to “ordinary” archaea and bacteria (DNA, same amino acids) Subtle differences: Cell membranes are made of lipids that are more stable to high temperature Additional enzyme (reverse DNA gyrase) causes DNA to fold up in a way that is more stable against heat The absolute maximum temperature is around 150 C--- DNA breaks up very readily above this temperature Slow growth of bacteria in thermafrost down to -20C YNP-Octopus Spring (White Creek area) Microbial mat.
    [Show full text]
  • Method for Prediction of Protein Function from Sequence Using The
    Article No. mb981993 J. Mol. Biol. (1998) 281, 949±968 Method for Prediction of Protein Function from Sequence using the Sequence-to-Structure-to- Function Paradigm with Application to Glutaredoxins/ Thioredoxins and T1 Ribonucleases Jacquelyn S. Fetrow1 and Jeffrey Skolnick2* 1Department of Biological The practical exploitation of the vast numbers of sequences in the gen- Sciences, Center for ome sequence databases is crucially dependent on the ability to identify Biochemistry and Biophysics the function of each sequence. Unfortunately, current methods, including University at Albany, SUNY global sequence alignment and local sequence motif identi®cation, are 1400 Washington Avenue limited by the extent of sequence similarity between sequences of Albany, NY 12222, USA unknown and known function; these methods increasingly fail as the sequence identity diverges into and beyond the twilight zone of sequence 2Department of Molecular identity. To address this problem, a novel method for identi®cation of Biology, The Scripps Institute protein function based directly on the sequence-to-structure-to-function 10550 North Torrey Pines paradigm is described. Descriptors of protein active sites, termed ``fuzzy Road, La Jolla, CA 92037, USA functional forms'' or FFFs, are created based on the geometry and confor- mation of the active site. By way of illustration, the active sites respon- sible for the disul®de oxidoreductase activity of the glutaredoxin/ thioredoxin family and the RNA hydrolytic activity of the T1 ribonuclease family are presented. First, the FFFs are shown to correctly identify their corresponding active sites in a library of exact protein models produced by crystallography or NMR spectroscopy, most of which lack the speci- ®ed activity.
    [Show full text]