Jeremy C. Mottram
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View article: From mitochondrial DNA arrangement to repair: a kinetoplast-associated protein with different roles in two trypanosomatid species
From mitochondrial DNA arrangement to repair: a kinetoplast-associated protein with different roles in two trypanosomatid species Open
View article: <i>Leishmania mexicana</i> pathogenicity requires flagellar assembly but not motility
<i>Leishmania mexicana</i> pathogenicity requires flagellar assembly but not motility Open
Protists of the order Trypanosomatida possess a single multifunctional flagellum, which powers cellular displacement and mediates attachment to tissues of the arthropod vector. The kinetoplastid flagellar cytoskeleton consists of a nine-mi…
View article: Structure and activity of the essential UCH family deubiquitinase DUB16 from <i>Leishmania donovani</i>
Structure and activity of the essential UCH family deubiquitinase DUB16 from <i>Leishmania donovani</i> Open
In Leishmania parasites, as for their hosts, the ubiquitin (Ub) proteasome system is important for cell viability. As part of a systematic gene deletion study, it was discovered that four cysteine protease-type deubiquitinases (DUBs) are e…
View article: Discovery and characterization of cell-permeable inhibitors of<i>Leishmania mexicana</i>CLK1 using an in-cell target engagement assay
Discovery and characterization of cell-permeable inhibitors of<i>Leishmania mexicana</i>CLK1 using an in-cell target engagement assay Open
Leishmaniasis is a neglected tropical disease with limited treatment options and significant unmet medical need. Here, we report the development of a bioluminescence resonance energy transfer (BRET)-based target engagement assay in live in…
View article: Structural analysis of RmlD, a dTDP-6-deoxy-L-lyxo-4-hexulose reductase from Trichomonas vaginalis
Structural analysis of RmlD, a dTDP-6-deoxy-L-lyxo-4-hexulose reductase from Trichomonas vaginalis Open
Background RmlD is the last enzyme in the pathway responsible for the conversion of glucose-1 phosphate to dTDP-L-rhamnose, a key component of the lipoglycans found on the surface of a range of parasites. The pathway has been identified as…
View article: Characterization of a novel <i>Leishmania</i> antigen containing a repetitive domain and its potential use as a prophylactic and therapeutic vaccine
Characterization of a novel <i>Leishmania</i> antigen containing a repetitive domain and its potential use as a prophylactic and therapeutic vaccine Open
Human visceral leishmaniasis (HVL) is the second most lethal tropical parasitic disease. Currently, no prophylactic or therapeutic vaccines exist for HVL. Thus, the development of an efficacious vaccine is still needed. We previously perfo…
View article: Structure and Activity of the Essential UCH Family Deubiquitinase DUB16 from<i>Leishmania donovani</i>
Structure and Activity of the Essential UCH Family Deubiquitinase DUB16 from<i>Leishmania donovani</i> Open
In Leishmania parasites, as for their hosts, the ubiquitin proteasome system is important for cell viability. As part of a systematic gene deletion study, it was discovered that four cysteine protease type deubiquitinases (DUBs) are essent…
View article: Tubulin detyrosination shapes <i>Leishmania</i> cytoskeletal architecture and virulence
Tubulin detyrosination shapes <i>Leishmania</i> cytoskeletal architecture and virulence Open
Tubulin detyrosination has been implicated in various human disorders and is important for regulating microtubule dynamics. While in most organisms this modification is restricted to α-tubulin, in trypanosomatid parasites, it occurs on bot…
View article: Gene tagging and gene deletion resources for Leishmania mexicana MNYC/BZ/62/M379 Cas9/T7 strain
Gene tagging and gene deletion resources for Leishmania mexicana MNYC/BZ/62/M379 Cas9/T7 strain Open
primers_barcodes.csv: List of primer sequences necessary for N and C terminus gene tagging, as well as gene deletion in the Leishmania mexicana MNYC/BZ/62/M379 Cas9/T7 strain. Each row contains the gene name and the DF (downstream forward)…
View article: TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen
TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen Open
For the protozoan parasite Leishmania , completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acidic mamma…
View article: The global dispersal of visceral leishmaniasis occurred within human history
The global dispersal of visceral leishmaniasis occurred within human history Open
The Leishmania donovani species complex (LdSC) causes visceral leishmaniasis (VL), is present in Africa, Europe, the Middle East, Asia and the Americas, and causes 20-40,000 fatalities per year. Previous analyses concluded that dispersal o…
View article: Functional plasticity shapes neutrophil response to Leishmania major infection in susceptible and resistant strains of mice
Functional plasticity shapes neutrophil response to Leishmania major infection in susceptible and resistant strains of mice Open
Neutrophils rapidly infiltrate sites of infection and possess several microbicidal strategies, such as neutrophil extracellular traps release and phagocytosis. Enhanced neutrophil infiltration is associated with higher susceptibility to Le…
View article: IFT and BBSome proteins are required for Leishmania mexicana pathogenicity, but flagellar motility is dispensable
IFT and BBSome proteins are required for Leishmania mexicana pathogenicity, but flagellar motility is dispensable Open
Protists of the order Kinetoplastida possess a single multifunctional flagellum, which powers cellular displacement and mediates attachment to tissues of the arthropod vector. The kinetoplastid flagellar cytoskeleton consists of a nine-mic…
View article: LeishGEM: genome-wide deletion mutant fitness and protein localisations in Leishmania
LeishGEM: genome-wide deletion mutant fitness and protein localisations in Leishmania Open
LeishGEM is a genome-wide functional annotation community resource for Leishmania mexicana, where deletion mutant growth in vitro and in vivo is measured and protein localisation is determined by endogenous tagging and LOPIT-DC (localisati…
View article: TransLeish: Identification of membrane transporters essential for survival of intracellular<i>Leishmania</i>parasites in a systematic gene deletion screen
TransLeish: Identification of membrane transporters essential for survival of intracellular<i>Leishmania</i>parasites in a systematic gene deletion screen Open
Summary For the protozoan parasite Leishmania , completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acid…
View article: Formation of functional E3 ligase complexes with UBC2 and UEV1 of Leishmania mexicana
Formation of functional E3 ligase complexes with UBC2 and UEV1 of Leishmania mexicana Open
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 Leis…
View article: A promising pipeline of preclinical drug candidates for leishmaniasis and chronic Chagas’ disease
A promising pipeline of preclinical drug candidates for leishmaniasis and chronic Chagas’ disease Open
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 bc1 complex inhibitor as a…
View article: Formation of Functional E3 Ligase Complexes with Ubc2 and Uev1 of Leishmania Mexicana
Formation of Functional E3 Ligase Complexes with Ubc2 and Uev1 of Leishmania Mexicana Open
View article: Bromodomain Factor 5 as a Target for Antileishmanial Drug Discovery
Bromodomain Factor 5 as a Target for Antileishmanial Drug Discovery Open
Leishmaniases are a collection of neglected tropical diseases caused by kinetoplastid parasites in the genus Leishmania. Current chemotherapies are severely limited, and the need for new antileishmanials is of pressing international…
View article: Bromodomain Factor 5 as a Target for Antileishmanial Drug Discovery
Bromodomain Factor 5 as a Target for Antileishmanial Drug Discovery Open
Leishmaniases are a collection of neglected tropical diseases caused by kinetoplastid parasites in the genus Leishmania. Current chemotherapies are severely limited and the need for new antileishmanials is of pressing international importa…
View article: <scp>AAK1</scp>‐like: A putative pseudokinase with potential roles in cargo uptake in bloodstream form <i>Trypanosoma brucei</i> parasites
<span>AAK1</span>‐like: A putative pseudokinase with potential roles in cargo uptake in bloodstream form <i>Trypanosoma brucei</i> parasites Open
Selection and internalization of cargo via clathrin‐mediated endocytosis requires adaptor protein complexes. One complex, AP‐2, acts during cargo selection at the plasma membrane. African trypanosomes lack all components of the AP‐2 comple…
View article: Autophagy in protists and their hosts: When, how and why?
Autophagy in protists and their hosts: When, how and why? Open
Pathogenic protists are a group of organisms responsible for causing a variety of human diseases including malaria, sleeping sickness, Chagas disease, leishmaniasis, and toxoplasmosis, among others. These diseases, which affect more than o…
View article: Genome sequence of Leishmania mexicana MNYC/BZ/62/M379 expressing Cas9 and T7 RNA polymerase
Genome sequence of Leishmania mexicana MNYC/BZ/62/M379 expressing Cas9 and T7 RNA polymerase Open
We present the genome sequence of Leishmania mexicana MNYC/BZ/62/M379 modified to express Cas9 and T7 RNA-polymerase, revealing high similarity to the reference genome (MHOM/GT2001/U1103). Through RNAseq-based annotation of coding sequence…
View article: Trypanosoma brucei rhodesiense Inhibitor of Cysteine Peptidase (ICP) Is Required for Virulence in Mice and to Attenuate the Inflammatory Response
Trypanosoma brucei rhodesiense Inhibitor of Cysteine Peptidase (ICP) Is Required for Virulence in Mice and to Attenuate the Inflammatory Response Open
The protozoan Trypanosoma brucei rhodesiense causes Human African Trypanosomiasis, also known as sleeping sickness, and penetrates the central nervous system, leading to meningoencephalitis. The Cathepsin L-like cysteine peptidase of T. b.…
View article: Genome sequence of Leishmania mexicana MNYC/BZ/62/M379 expressing Cas9 and T7 RNA polymerase
Genome sequence of Leishmania mexicana MNYC/BZ/62/M379 expressing Cas9 and T7 RNA polymerase Open
We present the genome sequence of Leishmania mexicana MNYC/BZ/62/M379 modified to express Cas9 and T7 RNA-polymerase, revealing high similarity to the reference genome (MHOM/GT2001/U1103). Through RNAseq-based annotation of coding sequence…
View article: 3′Nucleotidase/nuclease is required for Leishmania infantum clinical isolate susceptibility to miltefosine
3′Nucleotidase/nuclease is required for Leishmania infantum clinical isolate susceptibility to miltefosine Open
MRC GCRF and FAPES.
View article: CLK1/CLK2-driven signalling at the Leishmania kinetochore is captured by spatially referenced proximity phosphoproteomics
CLK1/CLK2-driven signalling at the Leishmania kinetochore is captured by spatially referenced proximity phosphoproteomics Open
View article: TORC1 is an essential regulator of nutrient-dependent differentiation in<i>Leishmania</i>
TORC1 is an essential regulator of nutrient-dependent differentiation in<i>Leishmania</i> Open
SUMMARY 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 …
View article: Parasite Genotype Is a Major Predictor of Mortality from Visceral Leishmaniasis
Parasite Genotype Is a Major Predictor of Mortality from Visceral Leishmaniasis Open
Multiple factors contribute to the risk of mortality from visceral leishmaniasis (VL), including, patient genotype, comorbidities, and nutrition. Many of these factors are influenced by socioeconomic biases.
View article: Ubiquitin and ubiquitin-like conjugation systems in trypanosomatids
Ubiquitin and ubiquitin-like conjugation systems in trypanosomatids Open
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 …