A5004985411- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Lysosomal Storage Disorders Research
- Genetics, Aging, and Longevity in Model Organisms
- Insect symbiosis and bacterial influences
- Calcium signaling and nucleotide metabolism
- Evolution and Genetic Dynamics
- Parasites and Host Interactions
- Biochemical and Molecular Research
- Cellular transport and secretion
- Photosynthetic Processes and Mechanisms
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Insect and Pesticide Research
- Mitochondrial Function and Pathology
- Toxoplasma gondii Research Studies
- Signaling Pathways in Disease
- Cytomegalovirus and herpesvirus research
- Macrophage Migration Inhibitory Factor
- Plant Virus Research Studies
- Immune Cell Function and Interaction
- Spectroscopy Techniques in Biomedical and Chemical Research
- Autophagy in Disease and Therapy
- DNA Repair Mechanisms
- Endoplasmic Reticulum Stress and Disease
Wellcome Centre for Molecular Parasitology
2012-2024
Wellcome Trust
2012-2024
University of Glasgow
2003-2021
Technion – Israel Institute of Technology
2012
The role of mammalian skin in harbouring and transmitting arthropod-borne protozoan parasites has been overlooked for decades as these pathogens have regarded primarily blood-dwelling organisms. Intriguingly, infections with low or undetected blood are common, particularly the case Human African Trypanosomiasis caused by Trypanosoma brucei gambiense. We hypothesise, therefore, represents an anatomic reservoir infection. Here we definitively show that substantial quantities trypanosomes exist...
Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and high-affinity pentamidine (HAPT1), but genetic identity of HAPT1 is unknown. We recently reported that loss T. aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites current study aims to delineate mechanism by which this occurs. The TbAQP2 loci isogenic pairs drug-susceptible MPXR strains subspecies were sequenced. Drug susceptibility profiles trypanosome...
Evolutionary theory predicts that the lack of recombination and chromosomal re-assortment in strictly asexual organisms results homologous chromosomes irreversibly accumulating mutations thus evolving independently each other, a phenomenon termed Meselson effect. We apply population genomics approach to examine this effect an important human pathogen, Trypanosoma brucei gambiense. determine T.b. gambiense is asexually derived from single progenitor, which emerged within last 10,000 years....
The World Health Organization (WHO) has recently announced its plan to eliminate Human African trypanosomiasis (HAT). plan's main focus is on the Trypanosoma brucei gambiense subspecies, which causes 97% of cases [1]. However, total elimination from certain areas proved extremely difficult previously; there been ongoing parasite detection in several foci West Africa, despite effective screening programmes. This focussed interest potential role asymptomatic human carriers contributing...
Abstract Background The diagnosis of gambiense human African trypanosomiasis (gHAT) typically involves 2 steps: a serological screen, followed by the detection living trypanosome parasites in blood or lymph node aspirate. Live can, however, remain undetected some seropositive individuals, who, we hypothesize, are infected with Trypanosoma brucei their extravascular dermis. Methods To test this hypothesis, conducted prospective observational cohort study gHAT focus Forecariah, Republic...
Human African trypanosomiasis (HAT), or sleeping sickness, is a fatal disease found throughout sub-Saharan Africa. The close to elimination in many areas, although it was similarly once before and subsequently reemerged, despite seemingly low rates of transmission. Determining how these foci persisted overcame an apparent transmission paradox key finally eliminating HAT. By assessing clinical, laboratory, mathematical data, we propose that asymptomatic infections contribute through the...
Trypanosoma brucei gambiense causes 97% of all cases African sleeping sickness, a fatal disease sub-Saharan Africa. Most species trypanosome, such as T. b. brucei, are unable to infect humans due the trypanolytic serum protein apolipoprotein-L1 (APOL1) delivered via two trypanosome lytic factors (TLF-1 and TLF-2). Understanding how overcomes these infects is major importance in fight against this disease. Previous work indicated that failure take up TLF-1 contributes resistance TLF-1,...
Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated important cell cycle processes such as mitotic spindle assembly disassembly, chromosome movement cytokinesis. Here we explore the function several enzyme homologues, katanins (KAT80, KAT60a, KAT60b KAT60c), spastin (SPA) fidgetin (FID) bloodstream stage African trypanosome parasite, Trypanosoma brucei. The cytoskeleton is based remains assembled throughout cycle, necessitating its...
SEC-23 is a component of coat protein complex II (COPII)-coated vesicles involved in the endoplasmic reticulum-to-Golgi transport pathway eukaryotes. During postembryonic life, Caenorhabditis elegans surrounded by collagenous exoskeleton termed cuticle. From screen for mutants defective cuticle secretion, we identified and characterized sec-23 mutant C. elegans. By sequence homology, has only single gene described herein. In addition to secretion defect, fail complete embryonic...
Apicomplexans are obligate intracellular parasites that invade the host cell in an active process relies on unique secretory organelles (micronemes, rhoptries and dense granules) localized at apical tip of these highly polarized eukaryotes. In order for contents specialized to reach their final destination, proteins sorted post‐Golgi it has been speculated they pass through endosomal‐like compartments ( ELC s), where undergo maturation. Here, we characterize a Toxoplasma gondii homologue...
Humans are protected against infection from most African trypanosomes by lipoprotein complexes present in serum that contain the trypanolytic pore-forming protein, Apolipoprotein L1 (APOL1). The human-infective trypanosomes, Trypanosoma brucei rhodesiense East Africa and T. b. gambiense West have separately evolved mechanisms allow them to resist APOL1-mediated lysis cause human trypanosomiasis, or sleeping sickness, man. Recently, APOL1 variants were identified a subset of Old World...
ABSTRACT The P2 aminopurine transporter, encoded by Tb AT1 in African trypanosomes the Trypanosoma brucei group, carries melaminophenyl arsenical and diamidine drugs into these parasites. Loss of this transporter contributes to drug resistance. We identified genomic location be subtelomeric region chromosome 5 determined status gene two trypanosome lines selected for resistance arsenical, melarsamine hydrochloride (Cymelarsan), a equiperdum clone diamidine, diminazene aceturate. In gambiense...
Trypanosoma brucei (T.b.) rhodesiense is the cause of acute form human African trypanosomiasis (HAT) in eastern and southern countries. There some evidence that there diversity disease progression T.b. different HAT Malawi associated with a chronic haemo-lymphatic stage infection compared to other countries, such as Uganda, where more marked neurological impairment. This has raised question role host genetic factors outcomes. A candidate gene association study was conducted northern region...
The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes Human African Trypanosomiasis. Its cell cycle complex not fully understood at molecular level. T. brucei genome contains over 6000 protein coding genes with >50% having no predicted function. A small scale RNA interference (RNAi) screen was carried out in to evaluate prospects for identifying novel regulators. Procyclic form were transfected a genomic RNAi library 204 clones isolated. However, only 76 found...
Human African Trypanosomiasis (HAT) has been responsible for several deadly epidemics throughout the 20th century, but a renewed commitment to disease control significantly reduced new cases and motivated target elimination of Trypanosoma brucei gambiense -HAT by 2030. However, recent identification latent human infections, detection trypanosomes in extravascular tissues hidden from current diagnostic tools, such as skin, added complexity identifying infected individuals. New improved tests...
Coordination between cell fate specification and cycle control in multicellular organisms is essential to regulate numbers tissues organs during development, its failure may lead oncogenesis. In mammalian cells, as part of a general checkpoint mechanism, the F-box protein beta-transducin repeat-containing (beta-TrCP) Skp1/Cul1/F-box complex periodic fluctuations abundance CDC25A B phosphatases. Here, we find that Caenorhabditis elegans beta-TrCP orthologue LIN-23 regulates progressive...
Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated important cell cycle processes such as mitotic spindle assembly disassembly, chromosome movement cytokinesis.Here we explore the function several enzyme homologues, katanins (KAT80, KAT60a, KAT60b KAT60c), spastin (SPA) fidgetin (FID) bloodstream stage African trypanosome parasite, Trypanosoma brucei.The cytoskeleton is based remains assembled throughout cycle, necessitating its...
Abstract Trypanosoma brucei gambiense and rhodesiense cause human African trypanosomiasis (HAT), a neglected tropical disease that constitutes an important public health issue in sub-Saharan Africa. In the absence of vaccine, only chemotherapy vector control has been used to combat disease. Environmental factors, such as exposure infected tsetse files, genetic factors variants APOL1 gene have shown contribute risk developing HAT. However, known explain small part trypanosomiasis. We...
Abstract Infections by many pathogens can result in a wide range of phenotypes, from severe to mild, or even asymptomatic. Understanding the genetic basis these phenotypes lead better tools treat patients detect reservoirs. To identify human factors that contribute symptoms diversity, we examined disease severities caused parasite T. b. gambiense , primary cause African trypanosomiasis (HAT). We analyzed transcriptomes immune cells both symptomatic HAT cases and individuals with latent...