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  1. Book ; Online: Chapter 48 In Vivo Bioluminescence Imaging to Assess Compound Efficacy Against Trypanosoma brucei

    Ritchie, Ryan / Barrett, Michael / Mottram, Jeremy / Myburgh, Elmarie

    2020  

    Keywords Biology, life sciences ; Firefly luciferase, Trypanosoma brucei brucei, In vivo imaging, Bioluminescence
    Size 1 electronic resource (17 pages)
    Publisher Springer Nature
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT021044641
    ISBN 9781071602966 ; 1071602969
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article ; Online: A promising pipeline of preclinical drug candidates for leishmaniasis and chronic Chagas' disease.

    Saldivia, Manuel / Lima, Ana Paula C A / Mottram, Jeremy C

    Trends in parasitology

    2024  Volume 40, Issue 3, Page(s) 211–213

    Abstract: The drug discovery pipeline for leishmaniasis and trypanosomiasis has been filling with novel chemical entities with known mechanisms of action. González et al. and Braillard et al. report a cytochrome ... ...

    Abstract The drug discovery pipeline for leishmaniasis and trypanosomiasis has been filling with novel chemical entities with known mechanisms of action. González et al. and Braillard et al. report a cytochrome bc
    MeSH term(s) Humans ; Chagas Disease/drug therapy ; Leishmaniasis/drug therapy ; Trypanosomiasis ; Leishmaniasis, Visceral/drug therapy ; Trypanosoma cruzi
    Language English
    Publishing date 2024-02-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2024.02.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tag Thy Neighbour: Nanometre-Scale Insights Into Kinetoplastid Parasites With Proximity Dependent Biotinylation.

    Geoghegan, Vincent / Mottram, Jeremy C / Jones, Nathaniel G

    Frontiers in cellular and infection microbiology

    2022  Volume 12, Page(s) 894213

    Abstract: Proximity labelling is a powerful and rapidly developing technology for exploring the interaction space and molecular environment of a protein of interest at the nanometre scale. In proximity labelling, a promiscuous biotinylating enzyme is genetically ... ...

    Abstract Proximity labelling is a powerful and rapidly developing technology for exploring the interaction space and molecular environment of a protein of interest at the nanometre scale. In proximity labelling, a promiscuous biotinylating enzyme is genetically fused to the protein of interest, initiation of labelling then results in the biotinylating enzyme generating reactive biotin which covalently 'tags' nearby molecules. Importantly, this labelling takes place
    MeSH term(s) Animals ; Biotin/metabolism ; Biotinylation ; Humans ; Kinetoplastida/metabolism ; Parasites/metabolism
    Chemical Substances Biotin (6SO6U10H04)
    Language English
    Publishing date 2022-05-06
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2022.894213
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Ubiquitin and ubiquitin-like conjugation systems in trypanosomatids.

    Burge, Rebecca J / Mottram, Jeremy C / Wilkinson, Anthony J

    Current opinion in microbiology

    2022  Volume 70, Page(s) 102202

    Abstract: In eukaryotic cells, reversible attachment of ubiquitin and ubiquitin-like modifiers (Ubls) to specific target proteins is conducted by multicomponent systems whose collective actions control protein fate and cell behaviour in precise but complex ways. ... ...

    Abstract In eukaryotic cells, reversible attachment of ubiquitin and ubiquitin-like modifiers (Ubls) to specific target proteins is conducted by multicomponent systems whose collective actions control protein fate and cell behaviour in precise but complex ways. In trypanosomatids, attachment of ubiquitin and Ubls to target proteins regulates the cell cycle, endocytosis, protein sorting and degradation, autophagy and various aspects of infection and stress responses. The extent of these systems in trypanosomatids has been surveyed in recent reports, while in Leishmania mexicana, essential roles have been defined for many ubiquitin-system genes in deletion mutagenesis and life-cycle phenotyping campaigns. The first steps to elucidate the pathways of ubiquitin transfer among the ubiquitination components and to define the acceptor substrates and the downstream deubiquitinases are now being taken.
    MeSH term(s) Ubiquitin/genetics ; Ubiquitin/metabolism ; Ubiquitination ; Proteins ; Eukaryotic Cells ; Autophagy
    Chemical Substances Ubiquitin ; Proteins
    Language English
    Publishing date 2022-09-11
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1418474-6
    ISSN 1879-0364 ; 1369-5274
    ISSN (online) 1879-0364
    ISSN 1369-5274
    DOI 10.1016/j.mib.2022.102202
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: In vitro Di-ubiquitin Formation Assay and E3 Cooperation Assay.

    Burge, Rebecca J / Jameson, Katie H / Wilkinson, Anthony J / Mottram, Jeremy C

    Bio-protocol

    2022  Volume 12, Issue 21

    Abstract: Ubiquitination is a post-translational modification conserved across eukaryotic species. It contributes to a variety of regulatory pathways, including proteasomal degradation, DNA repair, and cellular differentiation. The ubiquitination of substrate ... ...

    Abstract Ubiquitination is a post-translational modification conserved across eukaryotic species. It contributes to a variety of regulatory pathways, including proteasomal degradation, DNA repair, and cellular differentiation. The ubiquitination of substrate proteins typically requires three ubiquitination enzymes: a ubiquitin-activating E1, a ubiquitin-conjugating E2, and an E3 ubiquitin ligase. Cooperation between E2s and E3s is required for substrate ubiquitination, but some ubiquitin-conjugating E2s are also able to catalyze by themselves the formation of free di-ubiquitin, independently or in cooperation with a ubiquitin E2 variant. Here, we describe a method for assessing (i) di-ubiquitin formation by an E1 together with an E2 and an E2 variant, and (ii) the cooperation of an E3 with an E1 and E2 (with or without the E2 variant). Reaction products are assessed using western blotting with one of two antibodies: the first detects all ubiquitin conjugates, while the second specifically recognizes K63-linked ubiquitin. This allows unambiguous identification of ubiquitinated species and assessment of whether K63 linkages are present. We have developed these methods for studying ubiquitination proteins of
    Language English
    Publishing date 2022-11-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325 ; 2331-8325
    ISSN (online) 2331-8325
    ISSN 2331-8325
    DOI 10.21769/BioProtoc.4547
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Distinguishing functions of trypanosomatid protein kinases.

    Cayla, Mathieu / Nievas, Y Romina / Matthews, Keith R / Mottram, Jeremy C

    Trends in parasitology

    2022  Volume 38, Issue 11, Page(s) 950–961

    Abstract: Trypanosomatid parasitic protozoa are divergent from opisthokont models and have evolved unique mechanisms to regulate their complex life cycles and to adapt to a range of hosts. Understanding how these organisms respond, adapt, and persist in their ... ...

    Abstract Trypanosomatid parasitic protozoa are divergent from opisthokont models and have evolved unique mechanisms to regulate their complex life cycles and to adapt to a range of hosts. Understanding how these organisms respond, adapt, and persist in their different hosts could reveal optimal drug-control strategies. Protein kinases are fundamental to many biological processes such as cell cycle control, adaptation to stress, and cellular differentiation. Therefore, we have focused this review on the features and functions of protein kinases that distinguish trypanosomatid kinomes from other eukaryotes. We describe the latest research, highlighting similarities and differences between two groups of trypanosomatid parasites, Leishmania and African trypanosomes.
    MeSH term(s) Animals ; Leishmania/metabolism ; Life Cycle Stages ; Protein Kinases/metabolism ; Trypanosoma/metabolism
    Chemical Substances Protein Kinases (EC 2.7.-)
    Language English
    Publishing date 2022-09-05
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2022.08.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: TORC1 is an essential regulator of nutrient-controlled proliferation and differentiation in Leishmania.

    Myburgh, Elmarie / Geoghegan, Vincent / Alves-Ferreira, Eliza Vc / Nievas, Y Romina / Grewal, Jaspreet S / Brown, Elaine / McLuskey, Karen / Mottram, Jeremy C

    EMBO reports

    2024  Volume 25, Issue 3, Page(s) 1075–1105

    Abstract: Leishmania parasites undergo differentiation between various proliferating and non-dividing forms to adapt to changing host environments. The mechanisms that link environmental cues with the parasite's developmental changes remain elusive. Here, we ... ...

    Abstract Leishmania parasites undergo differentiation between various proliferating and non-dividing forms to adapt to changing host environments. The mechanisms that link environmental cues with the parasite's developmental changes remain elusive. Here, we report that Leishmania TORC1 is a key environmental sensor for parasite proliferation and differentiation in the sand fly-stage promastigotes and for replication of mammalian-stage amastigotes. We show that Leishmania RPTOR1, interacts with TOR1 and LST8, and identify new parasite-specific proteins that interact in this complex. We investigate TORC1 function by conditional deletion of RPTOR1, where under nutrient-rich conditions RPTOR1 depletion results in decreased protein synthesis and growth, G1 cell cycle arrest and premature differentiation from proliferative promastigotes to non-dividing mammalian-infective metacyclic forms. These parasites are unable to respond to nutrients to differentiate into proliferative retroleptomonads, which are required for their blood-meal induced amplification in sand flies and enhanced mammalian infectivity. We additionally show that RPTOR1
    MeSH term(s) Animals ; Leishmania ; Psychodidae/parasitology ; Phlebotomus/parasitology ; Nutrients ; Cell Proliferation ; Mammals
    Language English
    Publishing date 2024-02-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.1038/s44319-024-00084-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Formation of functional E3 ligase complexes with UBC2 and UEV1 of Leishmania mexicana.

    Burge, Rebecca J / Jameson, Katie H / Geoghegan, Vincent / Dowle, Adam A / Mottram, Jeremy C / Wilkinson, Anthony J

    Molecular and biochemical parasitology

    2024  Volume 258, Page(s) 111619

    Abstract: In eukaryotic cells, molecular fate and cellular responses are shaped by multicomponent enzyme systems which reversibly attach ubiquitin and ubiquitin-like modifiers to target proteins. The extent of the ubiquitin proteasome system in Leishmania mexicana ...

    Abstract In eukaryotic cells, molecular fate and cellular responses are shaped by multicomponent enzyme systems which reversibly attach ubiquitin and ubiquitin-like modifiers to target proteins. The extent of the ubiquitin proteasome system in Leishmania mexicana and its importance for parasite survival has recently been established through deletion mutagenesis and life-cycle phenotyping studies. The ubiquitin conjugating E2 enzyme UBC2, and the E2 enzyme variant UEV1, with which it forms a stable complex in vitro, were shown to be essential for the differentiation of promastigote parasites to the infectious amastigote form. To investigate further, we used immunoprecipitation of Myc-UBC2 or Myc-UEV1 to identify interacting proteins in L. mexicana promastigotes. The interactome of UBC2 comprises multiple ubiquitin-proteasome components including UEV1 and four RING E3 ligases, as well as potential substrates predicted to have roles in carbohydrate metabolism and intracellular trafficking. The smaller UEV1 interactome comprises six proteins, including UBC2 and shared components of the UBC2 interactome consistent with the presence of intracellular UBC2-UEV1 complexes. Recombinant RING1, RING2 and RING4 E3 ligases were shown to support ubiquitin transfer reactions involving the E1, UBA1a, and UBC2 to available substrate proteins or to unanchored ubiquitin chains. These studies define additional components of a UBC2-dependent ubiquitination pathway shown previously to be essential for promastigote to amastigote differentiation.
    MeSH term(s) Ubiquitin-Conjugating Enzymes/metabolism ; Ubiquitin-Conjugating Enzymes/genetics ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitin-Protein Ligases/genetics ; Protozoan Proteins/metabolism ; Protozoan Proteins/genetics ; Leishmania mexicana/genetics ; Leishmania mexicana/enzymology ; Leishmania mexicana/metabolism ; Protein Binding ; Protein Interaction Mapping ; Immunoprecipitation
    Chemical Substances Ubiquitin-Conjugating Enzymes (EC 2.3.2.23) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Protozoan Proteins
    Language English
    Publishing date 2024-03-29
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 756166-0
    ISSN 1872-9428 ; 0166-6851
    ISSN (online) 1872-9428
    ISSN 0166-6851
    DOI 10.1016/j.molbiopara.2024.111619
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Ubiquitin and Ubiquitin-like Conjugation Systems in Trypanosomatids

    Burge, Rebecca J. / Mottram, Jeremy C. / Wilkinson, Anthony J.

    Current opinion in microbiology. 2022 Aug. 11,

    2022  

    Abstract: In eukaryotic cells, reversible attachment of ubiquitin and ubiquitin-like modifiers (Ubls) to specific target proteins is conducted by multi-component systems whose collective actions control protein fate and cell behaviour in precise but complex ways. ... ...

    Abstract In eukaryotic cells, reversible attachment of ubiquitin and ubiquitin-like modifiers (Ubls) to specific target proteins is conducted by multi-component systems whose collective actions control protein fate and cell behaviour in precise but complex ways. In trypanosomatids, attachment of ubiquitin and Ubls to target proteins regulates the cell cycle, endocytosis, protein sorting and degradation, autophagy and various aspects of infection and stress responses. The extent of these systems in trypanosomatids has been surveyed in recent reports while in Leishmania mexicana, essential roles have been defined for many ubiquitin system genes in deletion mutagenesis and life-cycle phenotyping campaigns. The first steps to elucidate the pathways of ubiquitin transfer among the ubiquitination components and to define the acceptor substrates and the downstream deubiquitinases are now being taken.
    Keywords Leishmania mexicana ; autophagy ; cell cycle ; endocytosis ; microbiology ; mutagenesis ; phenotype ; ubiquitin ; ubiquitination ; ubiquitinyl hydrolase 1
    Language English
    Dates of publication 2022-0811
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 1418474-6
    ISSN 1879-0364 ; 1369-5274
    ISSN (online) 1879-0364
    ISSN 1369-5274
    DOI 10.1016/j.mib.2022.102202
    Database NAL-Catalogue (AGRICOLA)

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  10. Article: Distinguishing functions of trypanosomatid protein kinases

    Cayla, Mathieu / Nievas, Y. Romina / Matthews, Keith R. / Mottram, Jeremy C.

    Trends in parasitology. 2022,

    2022  

    Abstract: Trypanosomatid parasitic protozoa are divergent from opisthokont models and have evolved unique mechanisms to regulate their complex life cycles and to adapt to a range of hosts. Understanding how these organisms respond, adapt, and persist in their ... ...

    Abstract Trypanosomatid parasitic protozoa are divergent from opisthokont models and have evolved unique mechanisms to regulate their complex life cycles and to adapt to a range of hosts. Understanding how these organisms respond, adapt, and persist in their different hosts could reveal optimal drug-control strategies. Protein kinases are fundamental to many biological processes such as cell cycle control, adaptation to stress, and cellular differentiation. Therefore, we have focused this review on the features and functions of protein kinases that distinguish trypanosomatid kinomes from other eukaryotes. We describe the latest research, highlighting similarities and differences between two groups of trypanosomatid parasites, Leishmania and African trypanosomes.
    Keywords Leishmania ; Trypanosoma ; cell cycle ; cell differentiation ; drugs ; eukaryotic cells ; parasitology ; protein kinases
    Language English
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2022.08.009
    Database NAL-Catalogue (AGRICOLA)

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