DOCSLIB.ORG

Metabolic Network Analysis of Apicomplexan Parasites to Identify Novel Drug Targets

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Metabolic Network Analysis of Apicomplexan Parasites to Identify Novel Drug Targets Metabolic Network Analysis of Apicomplexan Parasites to Identify Novel Drug Targets by Stacy Susan Hung A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Molecular Genetics University of Toronto © Copyright by Stacy Susan Hung 2014 ii Metabolic Network Analysis of Apicomplexan Parasites to Identify Novel Drug Targets Stacy Susan Hung Doctor of Philosophy Molecular Genetics University of Toronto 2014 Abstract Parasites of the phylum Apicomplexa include many important human and veterinary pathogens such as Plasmodium (malaria), Toxoplasma (a leading opportunistic infection associated with AIDS and congenital neurological birth defects) and Eimeria (an economically significant disease of poultry and cattle). The lack of effective vaccines or treatments and increasing prevalence of drug-resistant strains stresses the urgency to develop novel drug therapies. Research presented within this thesis has provided numerous insights into the metabolic capabilities of apicomplexans and importantly, identifies potential enzyme drug targets offering a plethora of opportunities for further investigation and experimental validation. I first focused on generating a pipeline for accurately reconstructing metabolic networks by integrating enzyme annotations from complementary curated datasets and automated tools. Key to this integration is the Density Estimation Tool for Enzyme ClassificaTion (DETECT), a probabilistic method I developed for improved enzyme prediction accounting for sequence diversity across enzyme families. My comparative analyses across the resulting networks revealed that apicomplexans iii adopt differing strategies for performing similar core metabolic activities. Pantothenate biosynthesis was highlighted as a druggable pathway based on its conserved enzyme complement across the phylum and absence from the host. Using P. falciparum as a model for metabolism, I incorporated gene expression, thermodynamics and evolutionary data to gain insight into the operation of metabolic pathways in the parasite. Finally, the application of my metabolic reconstruction pipeline to other parasites illustrates its utility for establishing a meaningful characterization of metabolism for a newly sequenced organism, and when combined with additional experimental datasets provide a wealth of insights in the biology of these organisms. iv Acknowledgements I express my sincerest gratitude to my supervisor Dr. John Parkinson for giving me the opportunity to pursue my doctoral thesis in his lab. I am truly grateful for his insightful feedback and unwavering support throughout my Ph. D. degree. I would also like to thank all current and previous members of the Parkinson Lab, especially postdoc fellow Dr. James Wasmuth, who was an inspirational project mate and helped me feel grounded in my project. A special thanks to Alexandra Gast, Viviana Pszenny, and other members of Dr. Michael Grigg’s Lab at the NIH who have been instrumental in fast-forwarding my wet-lab expertise and knowledge of working with Toxoplasma parasites in the lab. Finally, I’d like to thank all my friends and family for their love, support, and encouragement. v Table of Contents Acknowledgements ........................................................................................................................ iv Table of Contents ............................................................................................................................ v List of Tables ................................................................................................................................. ix List of Figures ................................................................................................................................. x Chapter 1 Introduction .................................................................................................................... 1 1 Introduction ......................................................................................................................... 1 1.1 The Apicomplexa .......................................................................................................... 1 1.1.1 Taxonomy .............................................................................................................. 1 1.1.1.1 Genomes ............................................................................................................ 3 1.1.2 Epidemiology and Pathology ................................................................................ 5 1.1.2.1 Plasmodium ...................................................................................................... 5 1.1.2.2 Toxoplasma gondii ........................................................................................... 6 1.1.2.3 Cryptosporidium .............................................................................................. 7 1.1.2.4 Other Apicomplexa .......................................................................................... 8 1.1.3 General morphological features ............................................................................ 8 1.1.4 Life Cycle ............................................................................................................ 10 1.1.4.1 General life cycle of apicomplexans .............................................................. 10 1.1.4.2 Plasmodium falciparum life cycle .................................................................. 10 1.1.4.3 Toxoplasma gondii life cycle ......................................................................... 12 1.1.5 Population Genetics and Virulence ..................................................................... 13 1.1.5.1 Plasmodium .................................................................................................... 13 1.1.5.2 Toxoplasma gondii ......................................................................................... 13 1.1.6 Available drugs for the Apicomplexa ................................................................. 14 1.1.7 Metabolism as a source of drug targets ................................................................... 16 1.1.7.1 Enzymes are essential for life .......................................................................... 17 1.1.7.2 Mechanistic basis of enzymes for highly directed drug design ....................... 17 1.2 Experimental manipulations in the Apicomplexa ...................................................... 18 1.2.1 Methods for genetic manipulation ....................................................................... 18 1.2.1.1 Transfection and transformation .................................................................... 18 1.2.1.2 Gene knockouts .............................................................................................. 19 1.3 Metabolic reconstruction and analysis as a route to drug discovery .......................... 20 1.3.1 Metabolic reconstruction for the Apicomplexa ................................................... 21 1.3.2 Importance of enzyme annotation for metabolic reconstruction ......................... 23 vi 1.3.2.1 Enzyme annotation ......................................................................................... 23 1.3.2.2 Automated methods for enzyme prediction ................................................... 25 1.3.2.3 Curated resources for metabolic reconstruction ............................................. 26 1.3.3 Modelling, Network-based methods and FBA: Applications to drug discovery 28 1.4 Project goals ............................................................................................................... 31 Chapter 2 Improving enzyme annotation for accurate metabolic reconstruction ......................... 32 2 Improving enzyme annotation for accurate metabolic reconstruction .............................. 32 2.1 Introduction ................................................................................................................ 32 2.2 Materials and Methods ............................................................................................... 33 2.2.1 Protein sequence and enzyme data ...................................................................... 33 2.2.2 Generation of probability profiles ....................................................................... 34 2.2.3 Probability score calculation ............................................................................... 34 2.2.4 Five-fold cross-validation and ROC analysis ...................................................... 36 2.2.5 Prediction of malarial enzymes ........................................................................... 36 2.3 Results and Discussion ............................................................................................... 37 2.3.1 Assessing enzyme diversity ................................................................................ 37 2.3.2 Density estimation tool for enzyme classification (DETECT) ........................... 41 2.3.3 Comparison to current prediction methods ......................................................... 46 2.3.4 Expanding the metabolome of P. falciparum ...................................................... 52 2.4 Concluding Remarks .................................................................................................. 57 Chapter 3 Reconstructing parasite metabolism: Biological insights ............................................ 58 3 Reconstructing parasite
Load more

Recommended publications
  • University of Oklahoma
    UNIVERSITY OF OKLAHOMA GRADUATE COLLEGE MACRONUTRIENTS SHAPE MICROBIAL COMMUNITIES, GENE EXPRESSION AND PROTEIN EVOLUTION A DISSERTATION SUBMITTED TO THE GRADUATE FACULTY in partial fulfillment of the requirements for the Degree of DOCTOR OF PHILOSOPHY By JOSHUA THOMAS COOPER Norman, Oklahoma 2017 MACRONUTRIENTS SHAPE MICROBIAL COMMUNITIES, GENE EXPRESSION AND PROTEIN EVOLUTION A DISSERTATION APPROVED FOR THE DEPARTMENT OF MICROBIOLOGY AND PLANT BIOLOGY BY ______________________________ Dr. Boris Wawrik, Chair ______________________________ Dr. J. Phil Gibson ______________________________ Dr. Anne K. Dunn ______________________________ Dr. John Paul Masly ______________________________ Dr. K. David Hambright ii © Copyright by JOSHUA THOMAS COOPER 2017 All Rights Reserved. iii Acknowledgments I would like to thank my two advisors Dr. Boris Wawrik and Dr. J. Phil Gibson for helping me become a better scientist and better educator. I would also like to thank my committee members Dr. Anne K. Dunn, Dr. K. David Hambright, and Dr. J.P. Masly for providing valuable inputs that lead me to carefully consider my research questions. I would also like to thank Dr. J.P. Masly for the opportunity to coauthor a book chapter on the speciation of diatoms. It is still such a privilege that you believed in me and my crazy diatom ideas to form a concise chapter in addition to learn your style of writing has been a benefit to my professional development. I’m also thankful for my first undergraduate research mentor, Dr. Miriam Steinitz-Kannan, now retired from Northern Kentucky University, who was the first to show the amazing wonders of pond scum. Who knew that studying diatoms and algae as an undergraduate would lead me all the way to a Ph.D.
    [Show full text]
  • Confocal Raman Microscope Mapping As a Tool to Describe Different
    Biogeosciences, 8, 3761–3769, 2011 www.biogeosciences.net/8/3761/2011/ Biogeosciences doi:10.5194/bg-8-3761-2011 © Author(s) 2011. CC Attribution 3.0 License. Confocal Raman microscope mapping as a tool to describe different mineral and organic phases at high spatial resolution within marine biogenic carbonates: case study on Nerita undata (Gastropoda, Neritopsina) G. Nehrke1 and J. Nouet2 1Alfred Wegener Institute for Polar and Marine Research, Am Handelshafen 12, 27570 Bremerhaven, Germany 2University Paris Sud, IDES UMR 8148, batimentˆ 504, campus universitaire, 91405 Orsay cedex, France Received: 20 May 2011 – Published in Biogeosciences Discuss.: 9 June 2011 Revised: 10 November 2011 – Accepted: 7 December 2011 – Published: 20 December 2011 Abstract. Marine biogenic carbonates formed by inverte- 1 Introduction brates (e.g. corals and mollusks) represent complex compos- ites of one or more mineral phases and organic molecules. Calcium carbonates formed by marine calcifying organisms This complexity ranges from the macroscopic structures ob- (e.g. corals and mollusks) received much attention in the field served with the naked eye down to sub micrometric struc- of biogeosciences during the last decades. On the one hand tures only revealed by micro analytical techniques. Under- they represent important proxy archives (e.g. oxygen isotopic standing to what extent and how organisms can control the composition can be used for temperature reconstruction (Mc- formation of these structures requires that the mineral and Crea, 1950; Urey et al., 1951)) and on the other hand they are organic phases can be identified and their spatial distribution affected by the increasing acidification of the ocean due to related.
    [Show full text]
  • Polymorphic Protective Dps–DNA Co-Crystals by Cryo Electron Tomography and Small Angle X-Ray Scattering
    biomolecules Article Polymorphic Protective Dps–DNA Co-Crystals by Cryo Electron Tomography and Small Angle X-Ray Scattering Roman Kamyshinsky 1,2,3,* , Yury Chesnokov 1,2 , Liubov Dadinova 2, Andrey Mozhaev 2,4, Ivan Orlov 2, Maxim Petoukhov 2,5 , Anton Orekhov 1,2,3, Eleonora Shtykova 2 and Alexander Vasiliev 1,2,3 1 National Research Center “Kurchatov Institute”, Akademika Kurchatova pl., 1, 123182 Moscow, Russia; [email protected] (Y.C.); [email protected] (A.O.); [email protected] (A.V.) 2 Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics” of Russian Academy of Sciences, Leninskiy prospect, 59, 119333 Moscow, Russia; [email protected] (L.D.); [email protected] (A.M.); [email protected] (I.O.); [email protected] (M.P.); [email protected] (E.S.) 3 Moscow Institute of Physics and Technology, Institutsky lane 9, 141700 Dolgoprudny, Moscow Region, Russia 4 Shemyakin-Ovchinnikov Institute of bioorganic chemistry of Russian Academy of Sciences, Miklukho-Maklaya, 16/10, 117997 Moscow, Russia 5 Frumkin Institute of Physical Chemistry and Electrochemistry of Russian Academy of Sciences, Leninsky prospect, 31, 119071 Moscow, Russia * Correspondence: [email protected]; Tel.: +7-916-356-3963 Received: 6 November 2019; Accepted: 22 December 2019; Published: 26 December 2019 Abstract: Rapid increase of intracellular synthesis of specific histone-like Dps protein that binds DNA to protect the genome against deleterious factors leads to in cellulo crystallization—one of the most curious processes in the area of life science at the moment. However, the actual structure of the Dps–DNA co-crystals remained uncertain in the details for more than two decades.
    [Show full text]
  • PROGRAMME ABSTRACTS AGM Papers
    The Palaeontological Association 63rd Annual Meeting 15th–21st December 2019 University of Valencia, Spain PROGRAMME ABSTRACTS AGM papers Palaeontological Association 6 ANNUAL MEETING ANNUAL MEETING Palaeontological Association 1 The Palaeontological Association 63rd Annual Meeting 15th–21st December 2019 University of Valencia The programme and abstracts for the 63rd Annual Meeting of the Palaeontological Association are provided after the following information and summary of the meeting. An easy-to-navigate pocket guide to the Meeting is also available to delegates. Venue The Annual Meeting will take place in the faculties of Philosophy and Philology on the Blasco Ibañez Campus of the University of Valencia. The Symposium will take place in the Salon Actos Manuel Sanchis Guarner in the Faculty of Philology. The main meeting will take place in this and a nearby lecture theatre (Salon Actos, Faculty of Philosophy). There is a Metro stop just a few metres from the campus that connects with the centre of the city in 5-10 minutes (Line 3-Facultats). Alternatively, the campus is a 20-25 minute walk from the ‘old town’. Registration Registration will be possible before and during the Symposium at the entrance to the Salon Actos in the Faculty of Philosophy. During the main meeting the registration desk will continue to be available in the Faculty of Philosophy. Oral Presentations All speakers (apart from the symposium speakers) have been allocated 15 minutes. It is therefore expected that you prepare to speak for no more than 12 minutes to allow time for questions and switching between presenters. We have a number of parallel sessions in nearby lecture theatres so timing will be especially important.
    [Show full text]
  • Magnesium Silicate on Chloroquine Phosphate, Against Plasmodium Berghei
    Ajuvant effect of a Synthetic Aluminium – Magnesium Silicate on chloroquine phosphate, against Plasmodium berghei. * Ezeibe Maduike, Elendu – Eleke Nnenna, Okoroafor Obianuju and Ngene Augustine Department of Veterinary Medicine, University of Nigeria, Nsukka. *Corresponding authur [email protected] Abstract Effect of a synthetic Aluminium – Magnesium Silicate (AMS) on antiplasmodial activity of chloroquine was tested.Plasmodium berghei infected mice were treated with 7 mg/ kg, 5 mg / kg and 3 mg / kg chloroquine, respectively.Subgroups in each experiment were treated with chloroquine alone and with chloroquine in AMS.Parasitaemia (%) of the group treated with 7 mg / kg was higher than that of the control.At 5 mg / kg, chloroquine treatment reduced parasitaemia from 3.60 to 2.46 (P = ).Incorporating chloroquine in AMS improved its ability to reduce P.berghei parasitaemia at 5 mg /kg and at 3 mg / kg, from 2.46 0.21 to 1.57 0.25 (P = ) and from 3.82 0.06 to 2.12 0.08 (P = ). It also increased mortality of mice treated at 7 mg / kg from 20 to 80 % (P = ). Key words: Antiplasmodial resistance, chloroquine toxicity, Aluminium – Magnesium Silicate, chloroquine phosphate. Background. Nature Precedings : hdl:10101/npre.2012.6749.1 Posted 2 Jan 2012 Protozoan parasites of the genus plasmodium are causative agents of malaria1, 2. Malaria is a zoonotic disease , affecting man, zoo primates, avian species and rodents3,4. It has also been reported that when species of plasmodium which infect animals were passaged in human volunteers they produced malaria in man5. In humans, malaria is cause of between one to three million deaths in sub saharan Africa every year 6.Malaria is not only an effect of poverty it is also a cause of poverty7.To combat malaria, most countries in Africa spend upto 40 % of their public health budget on the disease annually8.
    [Show full text]
  • Why the –Omic Future of Apicomplexa Should Include Gregarines Julie Boisard, Isabelle Florent
    Why the –omic future of Apicomplexa should include Gregarines Julie Boisard, Isabelle Florent To cite this version: Julie Boisard, Isabelle Florent. Why the –omic future of Apicomplexa should include Gregarines. Biology of the Cell, Wiley, 2020, 10.1111/boc.202000006. hal-02553206 HAL Id: hal-02553206 https://hal.archives-ouvertes.fr/hal-02553206 Submitted on 24 Apr 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Article title: Why the –omic future of Apicomplexa should include Gregarines. Names of authors: Julie BOISARD1,2 and Isabelle FLORENT1 Authors affiliations: 1. Molécules de Communication et Adaptation des Microorganismes (MCAM, UMR 7245), Département Adaptations du Vivant (AVIV), Muséum National d’Histoire Naturelle, CNRS, CP52, 57 rue Cuvier 75231 Paris Cedex 05, France. 2. Structure et instabilité des génomes (STRING UMR 7196 CNRS / INSERM U1154), Département Adaptations du vivant (AVIV), Muséum National d'Histoire Naturelle, CP 26, 57 rue Cuvier 75231 Paris Cedex 05, France. Short Title: Gregarines –omics for Apicomplexa studies
    [Show full text]
  • Biomineralization of Carbonates in Modern Microbial Sediments and Its Implications for CO₂ Sequestration
    Scholars' Mine Doctoral Dissertations Student Theses and Dissertations Spring 2014 Biomineralization of carbonates in modern microbial sediments and its implications for CO₂ sequestration Varun Gnanaprian Paul Follow this and additional works at: https://scholarsmine.mst.edu/doctoral_dissertations Part of the Geology Commons, and the Geophysics and Seismology Commons Department: Geosciences and Geological and Petroleum Engineering Recommended Citation Paul, Varun Gnanaprian, "Biomineralization of carbonates in modern microbial sediments and its implications for CO₂ sequestration" (2014). Doctoral Dissertations. 2138. https://scholarsmine.mst.edu/doctoral_dissertations/2138 This thesis is brought to you by Scholars' Mine, a service of the Missouri S&T Library and Learning Resources. This work is protected by U. S. Copyright Law. Unauthorized use including reproduction for redistribution requires the permission of the copyright holder. For more information, please contact [email protected]. BIOMINERALIZATION OF CARBONATES IN MODERN MICROBIAL SEDIMENTS AND ITS IMPLICATIONS FOR CO2 SEQUESTRATION by VARUN GNANAPRIAN PAUL A DISSERTATION Presented to the Faculty of the Graduate School of the MISSOURI UNIVERSITY OF SCIENCE AND TECHNOLOGY In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY in GEOLOGY AND GEOPHYSICS 2014 Approved by: David J. Wronkiewicz, Advisor Melanie R. Mormile, Co-Advisor Francisca Oboh-Ikuenobe Wan Yang Jamie S. Foster © 2014 Varun Gnanaprian Paul All Rights Reserved iii PUBLICATION DISSERTATION OPTION This dissertation is organized into four main sections. Section 1 (pages 1 to 17) introduces the two main research projects undertaken and states the hypotheses and objectives. Section 2 (pages 18 to 35) describes the sites, materials used and the experimental methodology that has been employed in all the projects.
    [Show full text]
  • Oborník M.& Lukeš, J. (2013) Cell Biology of Chromerids: Autotrophic
    CHAPTER EIGHT Cell Biology of Chromerids: Autotrophic Relatives to Apicomplexan Parasites Miroslav Oborník*,†,{,1, Julius Lukeš*,† *Biology Centre, Institute of Parasitology, Academy of Sciences of the Czech Republic, Cˇ eske´ Budeˇjovice, Czech Republic †Faculty of Science, University of South Bohemia, Cˇ eske´ Budeˇjovice, Czech Republic { Institute of Microbiology, Academy of Sciences of the Czech Republic, Trˇebonˇ, Czech Republic 1Corresponding author: e-mail address: [email protected] Contents 1. Introduction 334 2. Chromerida: A New Group of Algae Isolated from Australian Corals 337 2.1 C. velia: A new alga from Sydney Harbor 338 2.2 V. brassicaformis: An alga from the Great Barrier Reef 343 3. Life Cycle 346 4. Evolution of Exosymbiont 348 5. Evolution of Chromerid Organelles 350 5.1 Evolution of chromerid plastids 350 5.2 Reduced mitochondrial genomes of chromerids 354 5.3 Chromerosome: C. velia as a possible mixotroph 354 6. Metabolism of Chromerids 355 6.1 Unique pathway for tetrapyrrole biosynthesis 355 6.2 Other metabolic features of C. velia 359 7. Chromerids as Possible Symbionts of Corals 361 8. Conclusions 361 Acknowledgments 362 References 362 Abstract Chromerida are algae possessing a complex plastid surrounded by four membranes. Although isolated originally from stony corals in Australia, they seem to be globally dis- tributed. According to their molecular phylogeny, morphology, ultrastructure, structure of organellar genomes, and noncanonical pathway for tetrapyrrole synthesis, these algae are thought to be the closest known phototrophic relatives to apicomplexan par- asites. Here, we summarize the current knowledge of cell biology and evolution of this novel group of algae, which contains only two formally described species, but is appar- ently highly diverse and virtually ubiquitous in marine environments.
    [Show full text]
  • Microorganisms
    microorganisms Article Comparative Proteomics Analysis Reveals New Features of the Oxidative Stress Response in the Polyextremophilic Bacterium Deinococcus radiodurans Lihua Gao, Zhengfu Zhou, Xiaonan Chen, Wei Zhang, Min Lin and Ming Chen * Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China; [email protected] (L.G.); [email protected] (Z.Z.); [email protected] (X.C.); [email protected] (W.Z.); [email protected] (M.L.) * Correspondence: [email protected] Received: 20 February 2020; Accepted: 19 March 2020; Published: 23 March 2020 Abstract: Deinococcus radiodurans is known for its extreme resistance to ionizing radiation, oxidative stress, and other DNA-damaging agents. The robustness of this bacterium primarily originates from its strong oxidative resistance mechanisms. Hundreds of genes have been demonstrated to contribute to oxidative resistance in D. radiodurans; however, the antioxidant mechanisms have not been fully characterized. In this study, comparative proteomics analysis of D. radiodurans grown under normal and oxidative stress conditions was conducted using label-free quantitative proteomics. The abundances of 852 of 1700 proteins were found to significantly differ between the two groups. These differential proteins are mainly associated with translation, DNA repair and recombination, response to stresses, transcription, and cell wall organization. Highly upregulated expression was observed for ribosomal proteins such as RplB, Rpsl, RpsR, DNA damage response proteins (DdrA, DdrB), DNA repair proteins (RecN, RecA), and transcriptional regulators (members of TetR, AsnC, and GntR families, DdrI). The functional analysis of proteins in response to oxidative stress is discussed in detail. This study reveals the global protein expression profile of D. radiodurans in response to oxidative stress and provides new insights into the regulatory mechanism of oxidative resistance in D.
    [Show full text]
  • "Plastid Originand Evolution". In: Encyclopedia of Life
    CORE Metadata, citation and similar papers at core.ac.uk Provided by University of Queensland eSpace Plastid Origin and Advanced article Evolution Article Contents . Introduction Cheong Xin Chan, Rutgers University, New Brunswick, New Jersey, USA . Primary Plastids and Endosymbiosis . Secondary (and Tertiary) Plastids Debashish Bhattacharya, Rutgers University, New Brunswick, New Jersey, USA . Nonphotosynthetic Plastids . Plastid Theft . Plastid Origin and Eukaryote Evolution . Concluding Remarks Online posting date: 15th November 2011 Plastids (or chloroplasts in plants) are organelles within organisms that emerged ca. 2.8 billion years ago (Olson, which photosynthesis takes place in eukaryotes. The ori- 2006), followed by the evolution of eukaryotic algae ca. 1.5 gin of the widespread plastid traces back to a cyano- billion years ago (Yoon et al., 2004) and finally by the rise of bacterium that was engulfed and retained by a plants ca. 500 million years ago (Taylor, 1988). Photosynthetic reactions occur within the cytosol in heterotrophic protist through a process termed primary prokaryotes. In eukaryotes, however, the reaction takes endosymbiosis. Subsequent (serial) events of endo- place in the organelle, plastid (e.g. chloroplast in plants). symbiosis, involving red and green algae and potentially The plastid also houses many other reactions that are other eukaryotes, yielded the so-called ‘complex’ plastids essential for growth and development in algae and plants; found in photosynthetic taxa such as diatoms, dino- for example, the
    [Show full text]
  • Microbial Lithification in Marine Stromatolites and Hypersaline Mats
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by RERO DOC Digital Library Published in Trends in Microbiology 13,9 : 429-438, 2005, 1 which should be used for any reference to this work Microbial lithification in marine stromatolites and hypersaline mats Christophe Dupraz1 and Pieter T. Visscher2 1Institut de Ge´ ologie, Universite´ de Neuchaˆ tel, Rue Emile-Argand 11, CP 2, CH-2007 Neuchaˆ tel, Switzerland 2Center for Integrative Geosciences, Department of Marine Sciences, University of Connecticut, 1080 Shennecossett Road, Groton, Connecticut, 06340, USA Lithification in microbial ecosystems occurs when pre- crucial role in regulating sedimentation and global bio- cipitation of minerals outweighs dissolution. Although geochemical cycles. the formation of various minerals can result from After the decline of stromatolites in the late Proterozoic microbial metabolism, carbonate precipitation is pos- (ca. 543 million years before present), microbially induced sibly the most important process that impacts global and/or controlled precipitation continued throughout the carbon cycling. Recent investigations have produced geological record as an active and essential player in most models for stromatolite formation in open marine aquatic ecosystems [9,10]. Although less abundant than in environments and lithification in shallow hypersaline the Precambrian, microbial precipitation is observed in a lakes, which could be highly relevant for interpreting the multitude of semi-confined (physically or chemically)
    [Show full text]
  • (PAD) and Post-Translational Protein Deimination—Novel Insights Into Alveolata Metabolism, Epigenetic Regulation and Host–Pathogen Interactions
    biology Article Peptidylarginine Deiminase (PAD) and Post-Translational Protein Deimination—Novel Insights into Alveolata Metabolism, Epigenetic Regulation and Host–Pathogen Interactions Árni Kristmundsson 1,*, Ásthildur Erlingsdóttir 1 and Sigrun Lange 2,* 1 Institute for Experimental Pathology at Keldur, University of Iceland, Keldnavegur 3, 112 Reykjavik, Iceland; [email protected] 2 Tissue Architecture and Regeneration Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, UK * Correspondence: [email protected] (Á.K.); [email protected] (S.L.) Simple Summary: Alveolates are a major group of free living and parasitic organisms; some of which are serious pathogens of animals and humans. Apicomplexans and chromerids are two phyla belonging to the alveolates. Apicomplexans are obligate intracellular parasites; that cannot complete their life cycle without exploiting a suitable host. Chromerids are mostly photoautotrophs as they can obtain energy from sunlight; and are considered ancestors of the apicomplexans. The pathogenicity and life cycle strategies differ significantly between parasitic alveolates; with some causing major losses in host populations while others seem harmless to the host. As the life cycles of Citation: Kristmundsson, Á.; Erlingsdóttir, Á.; Lange, S. some are still poorly understood, a better understanding of the factors which can affect the parasitic Peptidylarginine Deiminase (PAD) alveolates’ life cycles and survival is of great importance and may aid in new biomarker discovery. and Post-Translational Protein This study assessed new mechanisms relating to changes in protein structure and function (so-called Deimination—Novel Insights into “deimination” or “citrullination”) in two key parasites—an apicomplexan and a chromerid—to Alveolata Metabolism, Epigenetic assess the pathways affected by this protein modification.
    [Show full text]