{"id":154,"date":"2021-12-06T12:16:21","date_gmt":"2021-12-06T11:16:21","guid":{"rendered":"http:\/\/wordpress.p604513.webspaceconfig.de\/research\/projektbereich-a\/"},"modified":"2023-11-07T12:16:27","modified_gmt":"2023-11-07T11:16:27","slug":"project-area-a","status":"publish","type":"page","link":"https:\/\/www.loewe-druid.de\/en\/research\/project-area-a\/","title":{"rendered":"Project area A"},"content":{"rendered":"\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-kcfy5hng-c60ba60d4b46ab87df1ea9ec6f8df768\">\n.flex_column.av-kcfy5hng-c60ba60d4b46ab87df1ea9ec6f8df768{\nborder-radius:0px 0px 0px 0px;\npadding:0px 0px 0px 0px;\n}\n<\/style>\n<div  class='flex_column av-kcfy5hng-c60ba60d4b46ab87df1ea9ec6f8df768 av_one_fourth  avia-builder-el-0  el_before_av_three_fourth  avia-builder-el-first  rahmen-headline-projects first flex_column_div av-zero-column-padding  '     ><style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-kclw4cx9-e108665fa20a2cf08fc3fad088f91d01\">\n#top .av-special-heading.av-kclw4cx9-e108665fa20a2cf08fc3fad088f91d01{\npadding-bottom:10px;\n}\nbody .av-special-heading.av-kclw4cx9-e108665fa20a2cf08fc3fad088f91d01 .av-special-heading-tag .heading-char{\nfont-size:25px;\n}\n.av-special-heading.av-kclw4cx9-e108665fa20a2cf08fc3fad088f91d01 .av-subheading{\nfont-size:15px;\n}\n<\/style>\n<div  class='av-special-heading av-kclw4cx9-e108665fa20a2cf08fc3fad088f91d01 av-special-heading-h1 blockquote modern-quote  avia-builder-el-1  avia-builder-el-no-sibling '><h1 class='av-special-heading-tag '  itemprop=\"headline\"  >Project area A:<\/h1><div class=\"special-heading-border\"><div class=\"special-heading-inner-border\"><\/div><\/div><\/div><\/div>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-kcfyqmua-545b5695fecd9f40cdfa826d685e23d9\">\n.flex_column.av-kcfyqmua-545b5695fecd9f40cdfa826d685e23d9{\nborder-radius:0px 0px 0px 0px;\npadding:0px 0px 0px 0px;\n}\n<\/style>\n<div  class='flex_column av-kcfyqmua-545b5695fecd9f40cdfa826d685e23d9 av_three_fourth  avia-builder-el-2  el_after_av_one_fourth  avia-builder-el-last  rahmen-accordion-projects border-left flex_column_div av-zero-column-padding  '     ><div class=\"togglecontainer toggle_close_all  avia-builder-el-5  avia-builder-el-no-sibling  enable_toggles projekte_toggle\"><section class=\"av_toggle_section\" >    <div role=\"tablist\" class=\"single_toggle\" data-tags=\"{Alle}\">        <p data-fake-id=\"#toggle-id-1\" class=\"toggler av-inherit-border-color\" role=\"tab\" tabindex=\"0\" aria-controls=\"1toggle-id-container\"><span class=\"project_nr\"> A1<\/span><span class=\"project_title\">Protein\/protein interactions of Ebola virus proteins as targets for new antiviral strategies<\/span><br><span class=\"project_names\">Stephan Becker<\/span><span class=\"toggle_icon\">        <span class=\"vert_icon\"><\/span><span class=\"hor_icon\"><\/span><\/span><\/p>        <div id=\"toggle-id-1-container\" class=\"toggle_wrap\">            <div class=\"toggle_content invers-color invers-color  av-inherit-border-color flex-container\">              <div class=\"projekt-names one_three\"><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/stephan-becker.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/stephan-becker.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Prof. Dr. Stephan Becker<\/strong><\/p><p><p>Institut f\u00fcr Virologie<br \/>\nPhilipps-Universit\u00e4t Marburg<br \/>\nHans-Meerwein-Str. 2<br \/>\n35043 Marburg<br \/>\nPhone: +49 (0)6421-28 66253<br \/>\nE-Mail: <a class=\"mail\" href=\"mailto:becker@staff.uni-marburg.de\">becker(at)staff.uni-marburg(dot)de<\/a><\/p>\n<\/p><\/div><hr><\/div>\t\t\t <div class=\"project-content two_three border-left\"><div id=\"attachment_1614\" style=\"width: 188px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-1614\" class=\"wp-image-1614 size-full\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a1.a.png\" alt=\"\" width=\"178\" height=\"237\" \/><p id=\"caption-attachment-1614\" class=\"wp-caption-text\">Electronmicroscopic picture of Ebola virus leaving an infected cell (red arrow). \u00a9Schauflinger<\/p><\/div>\n<p><strong>Project description <\/strong><\/p>\n<p>The Ebola virus (EBOV) causes severe fever with extraordinarily high fatality rates. The matrix protein VP40 of EBOV plays key roles for the virus replication cycle and is regulated by homooligomerization. VP40 <strong>dimerization<\/strong> is crucial for the protein\u2019s transport towards the plasma membrane where the dimers polymerize resulting in <strong>filament formation<\/strong> which enables virus budding. VP40 <strong>octamerization<\/strong> results in the down-regulation of viral RNA synthesis. Due to their central role as building blocks of the higher-order oligomers, dimers represent a promising target for antiviral intervention. A <strong>fragment-based approach<\/strong> was used to identify hits binding to VP40 crystals which will be developed into lead compounds in order to inhibit VP40 oligomerization.<\/p>\n<p><strong>Scientific goal:<\/strong><\/p>\n<div id=\"attachment_1612\" style=\"width: 310px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-1612\" class=\"wp-image-1612 size-medium\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/\/a1.b-300x226.png\" alt=\"\" width=\"300\" height=\"226\" srcset=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a1.b-300x226.png 300w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a1.b.png 474w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><p id=\"caption-attachment-1612\" class=\"wp-caption-text\">High-resolution crystal Structure of Ebola virus VP40 Dimers. \u00a9Anke Werner<\/p><\/div>\n<p>The project aims to develop lead molecules into antiviral compounds using structure-based drug design &#8211; a combination of protein crystallography with <em>in silico<\/em> methods &#8211; as well as cell culture experiments under BSL4- conditions for validation.<\/p>\n<p><strong>DRUID collaboration partners:<\/strong><\/p>\n<p>B1 Diederich\/Kolb lab, A4 Heine\/Reuter lab, D1 Steinmetzer lab, E3 Rahlfs\/Przyborski lab<\/p>\n<hr \/>\n<p>References A1: <strong>1.<\/strong> *Hartlieb et al. (2007) PNAS 104: 624-9 <strong>2.<\/strong> *Hartlieb et al., (2003) J. Biol. Chem. 278: 41830-6 <strong>3.<\/strong> *Hoenen et al. (2005) J Virol. 79: 1898-905 <strong>4.<\/strong> *M\u00f6ller et al. 79, 14876-86 (2005) J Virol. <strong>5.<\/strong> Hoenen et al. (2010) J Virol 84: 7053-63. <strong>6.<\/strong> *Gomis-Ruth et al. (2003) Structure 11: 423-33.<br \/>\n* own project-specific preliminary work<\/p>\n<\/div>            <\/div>        <\/div>    <\/div><\/section><section class=\"av_toggle_section\" >    <div role=\"tablist\" class=\"single_toggle\" data-tags=\"{Alle}\">        <p data-fake-id=\"#toggle-id-1\" class=\"toggler av-inherit-border-color\" role=\"tab\" tabindex=\"0\" aria-controls=\"1toggle-id-container\"><span class=\"project_nr\"> A2<\/span><span class=\"project_title\">Development of eIF4A inhibitors as drug candidates and characterization of eIF4A-variants in Pathogens<\/span><br><span class=\"project_names\">Arnold Gr\u00fcnweller<\/span><span class=\"toggle_icon\">        <span class=\"vert_icon\"><\/span><span class=\"hor_icon\"><\/span><\/span><\/p>        <div id=\"toggle-id-1-container\" class=\"toggle_wrap\">            <div class=\"toggle_content invers-color invers-color  av-inherit-border-color flex-container\">              <div class=\"projekt-names one_three\"><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/arnold-gruenweller.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/arnold-gruenweller.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Prof. Dr. Arnold Gr\u00fcnweller<\/strong><\/p><p><p>Philipps-Universit\u00e4t Marburg<br \/>\nBau C<br \/>\nMarbacher Weg 6<br \/>\n35032 Marburg<br \/>\nTel.: +49 (0)6421-<span class=\"icon\">2825849<\/span><br \/>\nFax: +49 (0)6421-28 25854<br \/>\nE-Mail: <a class=\"mail\" href=\"arnold.gruenweller@staff.uni-marburg.de\">arnold.gruenweller(at)staff.uni-marburg(dot)de<\/a><\/p>\n<\/p><\/div><hr><\/div>\t\t\t <div class=\"project-content two_three border-left\"><p><strong>Project description<\/strong><\/p>\n<p>The cellular RNA helicase eIF4A is an excellent target for the development of broad-spectrum antivirals. During initiation of viral protein synthesis, many viruses, especially corona viruses, rely on this enzyme, which can efficiently and specifically be inhibited by rocaglates. In project A2, we would like to further develop rocaglates for potential clinical trials by e.g. nebulizing these compounds for local application into the respiratory tract and by creating a detailed side effect profile. In addition, new eIF4A inhibitors will be screened and characterized. \u00a0The systematic mutagenesis of known coronavirus sequences should allow a prediction of rocaglate sensitivity in newly emerging coronaviruses. Finally, the therapeutic relevance of rocaglates in different DRUID-relevant pathogens expressing eIF4A variants will be investigated.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-475 alignnone\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a2-grafik-01.gif\" alt=\"\" width=\"130\" height=\"14\" \/><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-medium wp-image-477 alignnone\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/\/a2-grafik-02-300x218.png\" alt=\"\" width=\"300\" height=\"218\" srcset=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a2-grafik-02-300x218.png 300w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a2-grafik-02.png 311w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/p>\n<div id=\"attachment_479\" style=\"width: 310px\" class=\"wp-caption alignnone\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-479\" class=\"wp-image-479 size-medium\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/\/a2-grafik-03-300x121.png\" alt=\"\" width=\"300\" height=\"121\" srcset=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a2-grafik-03-300x121.png 300w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a2-grafik-03.png 430w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><p id=\"caption-attachment-479\" class=\"wp-caption-text\">RNA clamping onto the surface of eIF4A by the rocaglate Silvestrol and evidence of inhibition of (corona)viral protein synthesis by the rocaglate CR-31-B (-).<\/p><\/div>\n<p><strong>Scientific goal:<\/strong><\/p>\n<p>Rocaglates will be further developed for their testing in clinical trials and the possibility to predict rocaglate sensitivity in emerging corona viruses and other DRUID-relevant pathogens will be evaluated.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>DRUID Collaboration partners<\/strong><strong>:<\/strong><\/p>\n<p>B2 Ziebuhr lab, B4 Grevelding lab, B5 Schlitzer lab, C6 H\u00e4berlein lab, D1 Friebertsh\u00e4user\/Steinmetzer lab, D3 van Zandbergen lab, D4 Hermosilla\/Mazurek\/Taubert lab, E4 Spengler lab, E6 Schiffmann lab<\/p>\n<hr \/>\n<p>References A2: <strong>1.<\/strong>*Biedenkopf et al., <strong>(2017), <em>Antiviral Res<\/em>. <\/strong>137: 76-81;<strong> 2.<\/strong> *M\u00fcller et al., <strong>(2018), <em>Antiviral Res<\/em>.<\/strong> 150:123-129; <strong>3.<\/strong> *Elgner et al., <strong>(2018), <em>Viruses.<\/em><\/strong> 10(4): 149; <strong>4.<\/strong> *Glitscher et al., <strong>(2018), <em>Viruses<\/em>. <\/strong>\u00a010(6): 301; <strong>5.<\/strong> *Hen\u00df et al., <strong>(2018), <em>Viruses.<\/em><\/strong> \u00a010(11): 592; <strong>6.<\/strong> *M\u00fcller et al., <strong>(2020), <em>Antiviral Res<\/em><\/strong>. 175:104706; *<strong>7.<\/strong> *M\u00fcller et al., <strong>(2021), <em>Antiviral Res.<\/em><\/strong> 186: 105012; <strong>8.<\/strong> *Blum et al., <strong>(2020), <em>J Cell Mol Med.<\/em><\/strong> 24(12): 6988-6999; [*own publications].<\/p>\n<\/div>            <\/div>        <\/div>    <\/div><\/section><section class=\"av_toggle_section\" >    <div role=\"tablist\" class=\"single_toggle\" data-tags=\"{Alle}\">        <p data-fake-id=\"#toggle-id-1\" class=\"toggler av-inherit-border-color\" role=\"tab\" tabindex=\"0\" aria-controls=\"1toggle-id-container\"><span class=\"project_nr\"> A3<\/span><span class=\"project_title\">Posttranslational protein modifications as Achilles\u2019 heel of pathogenic RNA viruses<\/span><br><span class=\"project_names\">Friedemann Weber<\/span><span class=\"toggle_icon\">        <span class=\"vert_icon\"><\/span><span class=\"hor_icon\"><\/span><\/span><\/p>        <div id=\"toggle-id-1-container\" class=\"toggle_wrap\">            <div class=\"toggle_content invers-color invers-color  av-inherit-border-color flex-container\">              <div class=\"projekt-names one_three\"><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/friedemann-weber.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/friedemann-weber.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Prof. Dr. Friedemann Weber<\/strong><\/p><p><p>Institut f\u00fcr Virologie<br \/>\nFB Veterin\u00e4rmedizin<br \/>\nJustus-Liebig-Universit\u00e4t Gie\u00dfen<br \/>\nSchubertstra\u00dfe 81<br \/>\n35392 Gie\u00dfen<br \/>\nPhone: +49 (0)641-99 38350<br \/>\nE-Mail: <a class=\"mail\" href=\"mailto:friedemann.weber@vetmed.uni-giessen.de\">friedemann.weber(at)vetmed.uni-giessen(dot)de<\/a><\/p>\n<\/p><\/div><hr><\/div>\t\t\t <div class=\"project-content two_three border-left\"><p><strong>Project description<\/strong><\/p>\n<p>Due to their small genome, viruses are highly dependent on functions of the host organism. Many of those functions are regulated by cell-encoded posttranslational protein modifications for which a substantial number of pharmaceutical inhibitors are available.<\/p>\n<p>Rift Valley Fever Virus (RVFV) is a mosquito-borne zoonotic pathogen endemic in parts of Africa. In large and devastating outbreaks, it typically kills thousands of farm animals and hundreds of humans. In the preceding funding period, we used a high-throughput genetic screen and identified a pro-viral host cell factor for RVFV that binds to posttranslational protein modifications. Inhibition of this factor in a human organoid model reduced viral RNA synthesis and progeny particle production. In addition, proteomic analyses showed that a viral protein is modified is a manner that the host cell factor can bind, and mutation of the relevant site led to a reduction of viral RNA synthesis.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Scientific goal:<\/strong><\/p>\n<p>We aim to elucidate the molecular mechanism and exploit it to specifically inhibit RVFV infection. Moreover, we will test available pharmaceutical inhibitors, and also screen for other pathogenic RNA viruses that may depend on this mechanism.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>DRUID Collaboration partners<\/strong><strong>:<\/strong><\/p>\n<p>A1 Becker, A2 Gr\u00fcnweller, B2 Ziebuhr, C1 Bender\/Hildt, D1 Friebertsh\u00e4user\/Steinmetzer, E3 Rahlfs\/ Przyborski, E4 Spengler,\u00a0E6 Schiffmann, E7P Krijnse Locker<\/p>\n<hr \/>\n<p>References A3: 1. Wuerth &amp; Weber (2016) Viruses 8, 174*. 2. Barr, Weber, Schmaljohn (2020) Fields Virology, vol 1, p 706-749*<\/p>\n<\/div>            <\/div>        <\/div>    <\/div><\/section><section class=\"av_toggle_section\" >    <div role=\"tablist\" class=\"single_toggle\" data-tags=\"{Alle}\">        <p data-fake-id=\"#toggle-id-1\" class=\"toggler av-inherit-border-color\" role=\"tab\" tabindex=\"0\" aria-controls=\"1toggle-id-container\"><span class=\"project_nr\"> A4<\/span><span class=\"project_title\">Search for lead structures to inhibit the chaperone IpgC from Shigella<\/span><br><span class=\"project_names\">Andreas Heine, Klaus Reuter<\/span><span class=\"toggle_icon\">        <span class=\"vert_icon\"><\/span><span class=\"hor_icon\"><\/span><\/span><\/p>        <div id=\"toggle-id-1-container\" class=\"toggle_wrap\">            <div class=\"toggle_content invers-color invers-color  av-inherit-border-color flex-container\">              <div class=\"projekt-names one_three\"><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/andreas-heine.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/andreas-heine.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Prof. Dr. Andreas Heine<\/strong><\/p><p><p>Institut f\u00fcr Pharmazeutische Chemie<br \/>\nMarbacher Weg 6<br \/>\n35032 Marburg<br \/>\nTel.: +49 (0)6421-28 21313<br \/>\nFax: +49 (0)6421-28 28994<br \/>\nE-Mail: <a class=\"mail\" href=\"mailto:heinea@staff.uni-marburg.de\">heinea(at)staff.uni-marburg(dot)de<\/a><\/p>\n<\/p><\/div><hr><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/klaus-reuter.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/klaus-reuter.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Prof. Dr. Klaus Reuter<\/strong><\/p><p><p>Institut f\u00fcr Pharmazeutische Chemie<br \/>\nPhilipps-Universit\u00e4t Marburg<br \/>\nMarbacher Weg 6<br \/>\n35032 Marburg<br \/>\nTel.: +49 (0)6421-28 25845<br \/>\nFax: +49 (0)6421-28 28994<br \/>\nE-Mail: <a class=\"mail\" href=\"mailto:reuterk@staff.uni-marburg.de\">reuterk(at)staff.uni-marburg(dot)de<\/a><\/p>\n<\/p><\/div><hr><\/div>\t\t\t <div class=\"project-content two_three border-left\"><p><strong>Project description<\/strong><\/p>\n<p>Bacteria of the genus <em>Shigella<\/em> invade the epithelial cells of the colon, which results in the severe inflammation of the large intestine. Known as bacterial dysentery or Shigellosis, this causes a large number of deaths, foremost in developing countries. The <em>Shigella<\/em> specific chaperone IpgC interacts with numerous further pathogenicity factors and is prerequisite for the virulence of this organism. In the absence of a \u201csubstrate protein\u201d, IpgC forms a homodimer, which is essential for its stability. We use IpgC as a target protein for the structure-based design of compounds against Shigellosis by preventing IpgC homodimer formation and\/or binding to substrate proteins. By now, we have established a protocol which reproducibly yields excellently diffracting IpgC crystals. Using a fragment-based approach, we have identified a number of IpgC \u201cbinders\u201d, some of which we were able to expand significantly. In addition to protein crystallography, we use \u201cMicroscale Thermophoresis\u201d, Isothermal Titration Calorimetry\u201d and a \u201cThermal Shift\u201d assay to study the influence of such molecules on homodimer formation, on the ability to interact with \u201csubstrates\u201d and on stability.<\/p>\n<div id=\"attachment_487\" style=\"width: 179px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-487\" class=\"wp-image-487 size-full\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a4-grafik-01.png\" alt=\"\" width=\"169\" height=\"178\" \/><p id=\"caption-attachment-487\" class=\"wp-caption-text\">Crystal struc-ture of ho-modimeric IpgC. \u00a9Klaus Reuter<\/p><\/div>\n<div id=\"attachment_485\" style=\"width: 191px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-485\" class=\"wp-image-485 size-full\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a4-grafik-02.png\" alt=\"\" width=\"181\" height=\"144\" \/><p id=\"caption-attachment-485\" class=\"wp-caption-text\">\u201cFollow up\u201d compound bound to IpgC. \u00a9Marina Gardonyi<\/p><\/div>\n<p><strong>Scientific goal:<\/strong><\/p>\n<p>In addition to further structural information on IpgC, our main goal is the optimization of the compounds identified so far using them as lead structures in the development of anti-Shigellosis compounds.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>DRUID Collaboration partners<\/strong><strong>:<\/strong><\/p>\n<p>A1 Stephan Becker, B1 Wibke Diederich \/ Peter Kolb, B7 Franco Falcone, D1 Eva Friebertsh\u00e4user \/ Torsten Steinmetzer<\/p>\n<hr \/>\n<p>References A4: <strong>[1]<\/strong> Agerberth et al. (2005) <em>World Health Organ<\/em> <strong>[2]<\/strong> Williams &amp; Berkley (2018) <em>Paediatr Int Child Health<\/em> 38:50-65. <strong>[3]<\/strong> Sansonetti (2001) <em>Am J Physiol Liver Physiol<\/em> 280:319-323. <strong>[4]<\/strong> Parsot et al. (2003) <em>Curr Opin Microbiol<\/em> 6:7-14. <strong>[5]<\/strong> Lunelli et al. (2009) Proc Natl Acad Sci USA 106:9661-9666.<\/p>\n<\/div>            <\/div>        <\/div>    <\/div><\/section><section class=\"av_toggle_section\" >    <div role=\"tablist\" class=\"single_toggle\" data-tags=\"{Alle}\">        <p data-fake-id=\"#toggle-id-1\" class=\"toggler av-inherit-border-color\" role=\"tab\" tabindex=\"0\" aria-controls=\"1toggle-id-container\"><span class=\"project_nr\"> A6<\/span><span class=\"project_title\">Targeting the highly divergent actin superfamily in malaria parasite transmission<\/span><br><span class=\"project_names\">Ross Douglas<\/span><span class=\"toggle_icon\">        <span class=\"vert_icon\"><\/span><span class=\"hor_icon\"><\/span><\/span><\/p>        <div id=\"toggle-id-1-container\" class=\"toggle_wrap\">            <div class=\"toggle_content invers-color invers-color  av-inherit-border-color flex-container\">              <div class=\"projekt-names one_three\"><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/ross-douglas.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/ross-douglas.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Dr. Ross Douglas<\/strong><\/p><p><p>Biomedical Research Center Seltersberg (BFS)<br \/>\nMolecular Infections Biology<br \/>\nJustus Liebig Universit\u00e4t Giessen<br \/>\nSchubertstrasse 81<br \/>\n35392 Gie\u00dfen<br \/>\nTel.: +49 (0)641-99 39145<br \/>\nFax: +49 (0)641-99 39129<br \/>\nE-Mail: <a class=\"mail\" href=\"mailto:ross.g.douglas@ernaehrung.uni-giessen.de\">ross.g.douglas(at)ernaehrung.uni-giessen(dot)de<\/a><\/p>\n<\/p><\/div><hr><\/div>\t\t\t <div class=\"project-content two_three border-left\"><p><strong>Project description<\/strong><\/p>\n<p>Malaria remains one of the most devastating diseases and is caused by single celled parasites called <em>Plasmodium<\/em>. These parasites are transmitted between people by <em>Anopheles<\/em> mosquitoes. The parasite needs a set of diverse proteins that enable it to transmit to the mosquito vector, including members of the highly divergent actin cytoskeleton and its regulators. The parasite cytoskeleton has unique properties in order to transmit and, given its essential nature in various parasite processes at different life cycle stages, contains promising targets for novel malaria therapies. We make use of target validation approaches to identify and characterize novel transmission blocking targets that could be used to control disease spread.<\/p>\n<div id=\"attachment_493\" style=\"width: 310px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-493\" class=\"wp-image-493 size-medium\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/\/a6-grafik-01-300x70.png\" alt=\"\" width=\"300\" height=\"70\" srcset=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a6-grafik-01-300x70.png 300w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a6-grafik-01-1030x241.png 1030w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a6-grafik-01-768x180.png 768w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a6-grafik-01-705x165.png 705w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/a6-grafik-01.png 1098w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><p id=\"caption-attachment-493\" class=\"wp-caption-text\">Target validation approach has identified novel transmission blocking targets.<\/p><\/div>\n<p><strong>Scientific goal:<\/strong><\/p>\n<p>We aim to characterize identified proteins of interest using a variety of <em>in vitro <\/em>and <em>in vivo<\/em> methods with a view to identify novel compounds that selectively target these proteins and thus serve as transmission blocking drug candidates.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>DRUID Collaboration partners<\/strong><strong>:<\/strong><\/p>\n<p>A7 Przyborski, B1 Diederich\/Kolb, B7 P Falcone,\u00a0E3 Rahlfs\/Przyborski<\/p>\n<hr \/>\n<p>References A6: [1] Douglas <em>et al.<\/em> <strong>(2018) <em>PLOS Bio<\/em> <\/strong>e2005345; [2] Douglas <em>et al.<\/em> <strong>(2018)<\/strong> <strong><em>Malaria J<\/em> <\/strong>17:3191898-905; [3] Douglas <em>et al.<\/em> <strong>(2015)<\/strong> <strong><em>Trends Parasitol <\/em><\/strong>31(8):357-362.<\/p>\n<\/div>            <\/div>        <\/div>    <\/div><\/section><section class=\"av_toggle_section\" >    <div role=\"tablist\" class=\"single_toggle\" data-tags=\"{Alle}\">        <p data-fake-id=\"#toggle-id-1\" class=\"toggler av-inherit-border-color\" role=\"tab\" tabindex=\"0\" aria-controls=\"1toggle-id-container\"><span class=\"project_nr\"> A7<\/span><span class=\"project_title\">Plasmodium chaperones, co-chaperones and their interactions as a target for drug development<\/span><br><span class=\"project_names\">Jude Przyborski<\/span><span class=\"toggle_icon\">        <span class=\"vert_icon\"><\/span><span class=\"hor_icon\"><\/span><\/span><\/p>        <div id=\"toggle-id-1-container\" class=\"toggle_wrap\">            <div class=\"toggle_content invers-color invers-color  av-inherit-border-color flex-container\">              <div class=\"projekt-names one_three\"><div class=\"project-name\"><div class=\"flex-container\"><div class=\"half\"><span class=\"principal\">Principal Investigator:<\/span><\/div><div class=\"half\"><a href=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/jude-przyborski.jpg\"><img decoding=\"async\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/pls2022\/jude-przyborski.jpg\" \/><\/a><\/div><\/div><p class=\"person_name\"><strong>Prof. Dr. Jude Przyborski<\/strong><\/p><p><p>Interdisziplin\u00e4res Forschungszentrum (iFZ)<br \/>\nJustus-Liebig-Universit\u00e4t Gie\u00dfen<br \/>\nHeinrich-Buff-Ring 26-32<br \/>\n35392 Gie\u00dfen<br \/>\nTel.: +49 (0)641-99 39114<br \/>\nE-Mail: <a class=\"mail \" href=\"mailto:jude.przyborski@ernaehrung.uni-giessen.de\">jude.przyborski(at)ernaehrung.uni-giessen(dot)de<\/a><\/p>\n<p><a href=\"https:\/\/www.uni-giessen.de\/fbz\/fb09\/institute\/ernaehrungswissenschaft\/prof\/becker\/mitarbeiter\/jude\">Homepage<\/a><\/p>\n<\/p><\/div><hr><\/div>\t\t\t <div class=\"project-content two_three border-left\"><p><strong>Project description<\/strong><\/p>\n<div id=\"attachment_361\" style=\"width: 310px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-361\" class=\"wp-image-361 size-medium\" src=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/\/projekt-a7-01-300x180.png\" alt=\"\" width=\"300\" height=\"180\" srcset=\"https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-a7-01-300x180.png 300w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-a7-01-768x461.png 768w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-a7-01-705x423.png 705w, https:\/\/www.loewe-druid.de\/wp-content\/uploads\/projekt-a7-01.png 817w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><p id=\"caption-attachment-361\" class=\"wp-caption-text\">Overview of assay design<\/p><\/div>\n<p>Malaria parasites invade and live within mature human red blood cells RBC). To enable their survival, the parasite renovates it\u2019s chosen host cell to its own advantage. Infected red blood cells become sticky and adhere to the lining of small blood vessels, and also coat themselves with proteins which enable them to become invisible the immune system. This unfortunately causes disease in the patient, and eventually leads to death. We have recently identified a number of important molecular players which are essential for this renovation process, including members of the so-called HSP70 and HSP40<\/p>\n<p>families. It is the goal of this project to block the function of HSP40 and HSP70. If we can do this, parasites are likely to be cleared from the bloodstream, relieving the severity of disease. To do this, we will establish a number of assays to measure the activity of HSP40\/HSP70, and use these to search for compounds which reduce this interaction. Promising compounds will then be tested directly on parasites for their ability to reduce host cell modification.<\/p>\n<hr \/>\n<p>References A7:<strong> 1. <\/strong>Diehl <em>et al.<\/em> (2021) <strong>PLoS Pathogens <\/strong>17:e1009969 <strong>2. <\/strong>Zhang <em>et al<\/em>. (2017) <strong>Sci Rep<\/strong> 7: 42188 <strong>3.<\/strong> Charnaud <em>et al.<\/em> (2017) <strong>PLoS One<\/strong> 12: e0181656 <strong>4.<\/strong> K\u00fclzer <em>et al.<\/em> (2012) <strong>Cell Micro<\/strong> 14: 1784-95 <strong>5.<\/strong> K\u00fclzer <em>et al.<\/em> (2010) <strong>Cell Micro<\/strong> 12: 1398-1420<\/p>\n<\/div>            <\/div>        <\/div>    <\/div><\/section><\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":0,"parent":140,"menu_order":9,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-154","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Project area A - LOEWE-Zentrum DRUID<\/title>\n<meta name=\"description\" content=\"Find here detailed information Project area A of LOEWE-DRUID\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.loewe-druid.de\/en\/research\/project-area-a\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Project area A - 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