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  • 1.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Jacobsson, Erik
    Uppsala University.
    Eriksson, Camilla
    Uppsala University.
    Hedström, Martin
    Lund University.
    Seth, Henrik
    Gothenburg University.
    McEvoy, Eric G
    Sundberg, Per
    Gothenburg University.
    Strand, Malin
    Swedish agricultural university (SLU).
    Discovery of peptide toxins in the world’s longest animal (The bootlace worm; Lineus longissimus): challenging claims of tetrodotoxin production.2015Konferensbidrag (Övrigt vetenskapligt)
  • 2.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Jacobsson, Erik
    Uppsala University.
    Eriksson, Camilla
    Uppsala University.
    Hedström, Martin
    Lund University.
    Seth, Henrik
    University of Gothenburg.
    McEvoy, Eric G
    Liverpool John Moores University.
    Sundberg, Per
    University of Gothenburg.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Göransson, Ulf
    Uppsala University.
    Discovery of peptide toxins in ribbon worms: challenging claims of tetrodotoxin production2015Konferensbidrag (Övrigt vetenskapligt)
  • 3.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Jacobsson, Erik
    Uppsala University.
    Eriksson, Camilla
    Uppsala University.
    Hedström, Martin
    Lund University.
    Seth, Henrik
    University of Gothenburg.
    Sundberg, Per
    University of Gothenburg.
    Rosengren, Johan
    University of Queensland.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Göransson, Ulf
    Uppsala University.
    The toxicity of ribbon worms: alpha-nemertides or tetrodotoxin, or both?2016Ingår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 82, nr Supplement 1, artikel-id P549Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    The marine ribbon worms (nemerteans) are predators which capture their prey by everting a proboscis carrying a mixture of toxins which brings on rapid paralysis [1]. Moreover, ribbon worms have a thick layer of epidermal mucus of similar constitution. Tetrodotoxin (TTX) has been identified as one of these toxins [2]. The extreme toxicity of TTX (lethal by ingestion of 0.5-2 mg) is due to its ability to block voltage-gated sodium channels. Although several bacterial species (among these Vibrio sp.) have been linked to its synthesis, the biogenic origin and biosynthesis is unclear. One hypothesis is that TTX production occurs in a symbiotic relationship with its host, in this case the ribbon worm [3]. We have made significant effort to identify TTX in a setup for production through the cultivation of Vibrio alginolyticus in nutrient broth infused with mucus from the ribbon worm Lineus longissimus. Toxicity was demonstrated by fraction injections into shore crabs, but no TTX was found, and it could be shown conclusively that toxicity was unrelated to TTX and the Vibrio culture itself, and rather a constituent of the ribbon worm mucus [4]. The following studies led us to the discovery of a new class of peptides, the alpha-nemertides, in the mucus of the ribbon worms, which could be directly linked to the toxic effects. A literature review of the available evidence for TTX in ribbon worms show that the evidence in most cases are indirect, although notable exceptions exist. This points to the necessity to further investigate the presence and roles of TTX and alpha-nemertides in ribbon worms.

  • 4.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Jacobsson, Erik
    Uppsala University.
    Eriksson, Camilla
    Uppsala University.
    Rosengren, K. Johan
    University of Queensland, Australia.
    Andrén, Per
    Uppsala University.
    Strand, Malin
    Swedish agricultural university (SLU).
    Göransson, Ulf
    Uppsala University.
    Discovery of peptide toxins in the bootlace worm, the world's longest animal2015Konferensbidrag (Övrigt vetenskapligt)
  • 5.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB). Uppsala university.
    Jacobsson, Erik
    Uppsala University.
    Laborde, Quentin
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Rosengren, Johan
    University of Queensland, Australia.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Göransson, Ulf
    Uppsala University.
    Alpha-nemertides - a novel family of nemertean peptide neurotoxins2018Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    We recently discovered a novel family of neuroactive peptides in nemerteans, which we have named alpha-nemertides (1). One of these peptides, nemertide alpha-1, has been the subject of detailed studies with regard to structure and effects. The peptide exhibits exceptional potency against a number of arthropod species. Moreover, in vitro experiments suggest that alpha-1 acts primarily on voltage-gated sodium channels, and that this action is selective for arthropods by two orders of magnitude over vertebrate species. Using transcriptomic and proteomic approaches, we have identified 10 alpha-nemertides, but this number is likely to increase. These peptides alongside with a series of mutants are currently under evaluation by our group, with the goal to improve our understanding of structure-function relationships. In addition, we are considering potential practical uses of alpha-nemertides. In this talk, I will describe the current status of this research project.

    1. E. Jacobsson et al., Peptide ion channel toxins from the bootlace worm, the longest animal on Earth. Scientific reports 8, 4596 (2018).

  • 6.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Jacobsson, Erik
    Uppsala University.
    Rosengren, Johan
    University of Queensland, Australia.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Göransson, Ulf
    Uppsala University.
    Discovery of novel ion-channel active peptide toxins in a North Sea Ribbon Worm2016Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Ribbon worms (nemerteans) are marine predators, which capture their prey using a proboscis containing a mixture of toxins which brings on rapid paralysis [1]. In addition, their epidermis contains thick mucus of similar toxic constitution. One very potent toxin reported in ribbon worm mucus is tetrodotoxin (TTX). However, despite significant efforts, Strand et al. [2] were unable to detect any TTX, neither in the mucus of the ribbon worm Lineus longissimus, nor from Vibrio alginolyticus cultures isolated from and cultivated in the mucus. These observations challenged the notion of general presence of TTX in ribbon worm mucus, and prompted us to look for other toxins [3]. Using LC-MS analysis of mucus extracts, we identified three peptides present in significant amounts. The peptides were sequenced using a combination of MS/MS analysis and transcriptomics, and whereas one of them strongly resembles the only peptide toxin previously characterized from ribbon worms, Neurotoxin B-IV [4], the other two were found to represent a previously unknown class of peptide toxins. The most abundant of these was synthesized, and its 3D structure determined. Preliminary toxicity tests on shore crab (C. maenas) indicated toxicity (through paralysis) on par with that of TTX. Further analyses have indicated that its toxic effects are due to binding to voltage sensitive sodium channels.

     

    With L. longissimus as our primary target, we are now mapping the presence of peptide toxins in ribbon worms, with the objectives to establish routes for synthesis, and to characterize the biological activities and structures of these peptides. The number of peptides of this novel class is increasing, and synthesis and characterization is well underway. The striking potencies of these peptides make them potentially amenable as novel insecticidal or anthelmintic leads, pharmacological tools or in biotechnology applications.

     

    References

    1. Strand M, Sundberg P. Nationalnyckeln till Sveriges flora och fauna [DO-DP]. Stjärnmaskar-Slemmaskar: Sipuncula-Nemertea: Artdatabanken, SLU; 2010.

    2. Strand M, Hedstrom M, Seth H, McEvoy EG, Jacobsson E, Goransson U, Andersson HS, Sundberg P. The Bacterial (Vibrio alginolyticus) Production of Tetrodotoxin in the Ribbon Worm Lineus longissimus-Just a False Positive? Marine Drugs. 2016;14(4).

    3. Strand M, Andersson HS. Slemmaskens hemlighet. Forskning & Framsteg. 2016;(2):26-33.

    4. Blumenthal KM, Kem WR. Structure and action of heteronemertine polypeptide toxins. Primary structure of Cerebratulus lacteus toxin B-IV. The Journal of Biological Chemistry. 1976;251(19):6025-9.

  • 7.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Jacobsson, Erik
    Uppsala University.
    Rosengren, Johan
    University of Queensland, Australia.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Göransson, Ulf
    Uppsala University.
    Mapping the diversity of nemertean peptide toxins2018Konferensbidrag (Övrigt vetenskapligt)
  • 8.
    Andersson, Håkan S.
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Jacobsson, Erik
    Uppsala University.
    Strand, Malin
    Swedish agricultural university (SLU).
    Peigneur, Steve
    University of Leuven (KU Leuven), Belgium.
    Lebbe, Eline
    University of Leuven (KU Leuven), Belgium.
    Rosengren, Johan
    University of Queensland.
    Tytgat, Jan
    University of Leuven (KU Leuven), Belgium.
    Göransson, Ulf
    Uppsala University.
    Alpha-nemertides, a novel family of marine peptide neurotoxins from ribbon worms2017Konferensbidrag (Övrigt vetenskapligt)
  • 9.
    Göransson, Ulf
    et al.
    Uppsala University.
    Jacobsson, Erik
    Uppsala University.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Andersson, Håkan S.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    The toxins of nemertean worms2019Ingår i: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 11, nr 2, s. 1-36, artikel-id 120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Most ribbon worms (phylum: Nemertea) are found in marine environments, where they act as predators and scavengers. They are characterized by an eversible proboscis that is used to hunt for prey and thick mucus covering their skin. Both proboscis and epidermal mucus mediate toxicity to predators and preys. Research into the chemical nature of the substances that render toxicity has not been extensive, but it has nevertheless led to the identification of several compounds of potential medicinal use or for application in biotechnology. This review provides a complete account of the current status of research into nemertean toxins.

  • 10.
    Jacobsson, Erik
    et al.
    Uppsala University.
    Andersson, Håkan S.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Strand, Malin
    Swedish agricultural university (SLU).
    Eriksson, Camilla
    Uppsala University.
    Göransson, Ulf
    Uppsala University.
    Peptide toxins from L. longissimus: extraction, biological activity, structure and production2015Konferensbidrag (Övrigt vetenskapligt)
  • 11.
    Jacobsson, Erik
    et al.
    Uppsala University.
    Andersson, Håkan S.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Lebbe, Eline
    University of Leuven (KU Leuven), Belgium.
    Eriksson, Camilla
    Uppsala University.
    Peigneur, Steve
    University of Leuven (KU Leuven), Belgium.
    Rosengren, Johan
    University of Queensland, Australia.
    Tytgat, Jan
    University of Leuven (KU Leuven), Belgium.
    Göransson, Ulf
    Uppsala University.
    Peptide toxins from the longest animal on earth.2016Ingår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 82, nr Supplement 1, artikel-id YRW3Artikel i tidskrift (Övrigt vetenskapligt)
  • 12.
    Strand, Malin
    et al.
    Swedish University of Agricultural Sciences.
    Andersson, Håkan S.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Slemmaskens hemlighet2016Ingår i: Forskning & Framsteg, ISSN 0015-7937, nr 2, s. 26-33Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
    Abstract [sv]

    Nyckeln till framtidens mediciner kan gömma sig hos slemmiga, giftiga maskar som lever på havets botten. Här berättar marinbiologen Malin Strand och biokemisten Håkan Andersson om jakten som ledde till en oväntad upptäckt – och som tog slemmasken från det marinbiologiska laboratoriet på Tjärnö och Sveriges västkust till kemilaboratoriet i Uppsala.

  • 13.
    Strand, Malin
    et al.
    Swedish University of Agricultural Sciences ; Uppsala University.
    Hedström, Martin
    Lund University.
    Seth, Henrik
    University of Gothenburg.
    McEvoy, Eric G
    Liverpool John Moores University, UK.
    Jacobsson, Erik
    Uppsala University.
    Göransson, Ulf
    Uppsala University.
    Andersson, Håkan S.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Sundberg, Per
    University of Gothenburg.
    The Bacterial (Vibrio alginolyticus) Production of Tetrodotoxin in the Ribbon Worm Lineus longissimus: Just a False Positive?2016Ingår i: Marine Drugs, ISSN 1660-3397, E-ISSN 1660-3397, Vol. 14, nr 4, artikel-id 63Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We test previous claims that the bacteria Vibrio alginolyticus produces tetrodotoxin (TTX) when living in symbiosis with the nemertean Lineus longissimus by a setup with bacteria cultivation for TTX production. Toxicity experiments on the shore crab, Carcinus maenas, demonstrated the presence of a paralytic toxin, but evidence from LC-MS and electrophysiological measurements of voltage-gated sodium channel–dependent nerve conductance in male Wistar rat tissue showed conclusively that this effect did not originate from TTX. However, a compound of similar molecular weight was found, albeit apparently non-toxic, and with different LC retention time and MS/MS fragmentation pattern than those of TTX. We conclude that C. maenas paralysis and death likely emanate from a compound <5 kDa, and via a different mechanism of action than that of TTX. The similarity in mass between TTX and the Vibrio-produced low-molecular-weight, non-toxic compound invokes that thorough analysis is required when assessing TTX production. Based on our findings, we suggest that re-examination of some published claims of TTX production may be warranted.

  • 14.
    Strand, Malin
    et al.
    Swedish University of Agricultural Sciences.
    Norenburg, Jon
    Smithsonian Natl Museum Nat Hist, USA.
    Alfaya, Jose E.
    Univ Nacl Patagonia San Juan Bosco, Argentina.
    Angel Fernandez-Alvarez, Fernando
    CSIC, Spain.
    Andersson, Håkan S.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Andrade, Sonia C. S.
    Univ Sao Paulo, Brazil.
    Bartolomaeus, Thomas
    Univ Bonn, Germany.
    Beckers, Patrick
    Univ Bonn, Germany.
    Bigatti, Gregorio
    Univ Nacl Patagonia San Juan Bosco, Argentina.
    Cherneva, Irina
    Lomonosov Moscow State Univ, Russia.
    Chernyshev, Alexey
    Russian Acad Sci, Russia;Far Eastern Fed Univ, Russia.
    Chung, Brian M.
    Weber State Univ, USA.
    von Doehren, Joern
    Univ Bonn, Germany.
    Giribet, Gonzalo
    Harvard Univ, USA.
    Gonzalez-Cueto, Jaime
    Univ Magdalena, Colombia.
    Herrera-Bachiller, Alfonso
    Univ Alcala De Henares, Spain.
    Hiebert, Terra
    Univ Oregon, USA.
    Hookabe, Natsumi
    Hokkaido Univ, Japan.
    Junoy, Juan
    Univ Alcala De Henares, Spain.
    Kajihara, Hiroshi
    Hokkaido Univ, Japan.
    Kraemer, Daria
    Univ Bonn, Germany.
    Kvist, Sebastian
    Royal Ontario Museum, Canada;Univ Toronto, Canada.
    Magarlamov, Timur Yu
    Russian Acad Sci, Russia.
    Maslakova, Svetlana
    Univ Oregon, USA.
    Mendes, Cecili B.
    Univ Sao Paulo, Brazil.
    Okazaki, Robert
    Weber State Univ, USA.
    Sagorny, Christina
    Univ Bonn, Germany.
    Schwartz, Megan
    Univ Puget Sound, USA.
    Sun, Shi-Chun
    Ocean Univ China, Peoples Republic of China.
    Sundberg, Per
    University of Gothenburg.
    Turbeville, James M.
    Virginia Commonwealth Univ, USA.
    Xu, Cong-Mei
    Swedish University of Agricultural Sciences;Russian Acad Sci, Russia.
    Nemertean taxonomy-Implementing changes in the higher ranks, dismissing Anopla and Enopla2019Ingår i: Zoologica Scripta, ISSN 0300-3256, E-ISSN 1463-6409, Vol. 48, nr 1, s. 118-119Artikel i tidskrift (Refereegranskat)
1 - 14 av 14
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