A5024443171- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Insect symbiosis and bacterial influences
- Lysosomal Storage Disorders Research
- Immune Cell Function and Interaction
- Renal Diseases and Glomerulopathies
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Chronic Lymphocytic Leukemia Research
- T-cell and B-cell Immunology
- Calcium signaling and nucleotide metabolism
- Plant Virus Research Studies
- Evolution and Genetic Dynamics
- Vector-Borne Animal Diseases
- Insect and Pesticide Research
- Vector-borne infectious diseases
- Atherosclerosis and Cardiovascular Diseases
- Synthesis and Biological Evaluation
- Hemoglobinopathies and Related Disorders
- Celiac Disease Research and Management
- Fungal and yeast genetics research
- T-cell and Retrovirus Studies
- Parasitic Diseases Research and Treatment
- Acute Lymphoblastic Leukemia research
- Spectroscopy Techniques in Biomedical and Chemical Research
University of Glasgow
2015-2024
Wellcome Centre for Molecular Parasitology
2014-2024
Wellcome Trust
2014-2024
Public Health England
2017
London School of Hygiene & Tropical Medicine
2017
National Center for Global Health and Medicine
2017
University College Hospital
2017
University College London
2017
Instituut voor Tropische Geneeskunde
2017
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...
Reduced susceptibility to infectious disease can increase the frequency of otherwise deleterious alleles. In populations African ancestry, two apolipoprotein-L1 (APOL1) variants with a recessive kidney risk, named G1 and G2, occur at high frequency. APOL1 is trypanolytic protein that confers innate resistance most trypanosomes, but not Trypanosoma brucei rhodesiense or T.b. gambiense, which cause human trypanosomiasis. this case-control study, we test prevailing hypothesis these reduce...
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....
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...
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,...
We describe 2 spatially distinct foci of human African trypansomiasis in eastern Uganda. The Tororo and Soroti Trypanosoma brucei rhodesiense infection were genetically as characterized by 6 microsatellite 1 minisatellite polymorphic markers differences disease progression host-immune response. In particular, infections with the genotype exhibited an increased frequency to severity meningoencephalitic stage higher plasma interferon (IFN)-γ concentration, compared those genotype. propose that...
Objective High sensitivity plasma cardiac troponin-I (cTnI) is emerging as a strong predictor of events in variety settings. We have explored its utility patients with myotonic dystrophy type 1 (DM1). Methods 117 DM1 were recruited from routine outpatient clinics across three health boards. A single measurement cTnI was made using the ARCHITECT STAT Troponin I assay. Demographic, ECG, echocardiographic and other clinical data obtained electronic medical records. Follow up for mean 23 months....
Abstract African trypanosomes colonise the skin to ensure parasite transmission. However, how responds trypanosome infection remains unresolved. Here, we investigate local immune response of in a murine model using spatial and single cell transcriptomics. We detect expansion dermal IL-17A-producing Vγ6 + cells during infection, which occurs subcutaneous adipose tissue. In silico cell-cell communication analysis suggests that interstitial preadipocytes trigger T activation via Cd40 Tnfsf18...
African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock East Southern Africa, has classically been described host-range variant non-human infective occurs stable clonal lineages. We have examined T. b. rhodesiense populations from (Uganda) (Malawi) Africa using panel...
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...
In contrast to Trypanosoma brucei gambiense and T. b. rhodesiense (the causative agents of human African trypanosomiasis), is lysed by apolipoprotein-L1 (apoL1)-containing serum trypanolytic factors (TLF), rendering it non-infectious humans. While the mechanisms TLF1 uptake, apoL1 membrane integration, apoL1-resistance have been extensively characterised, our understanding range that drive action in limited. Selecting bloodstream-form RNAi library with recombinant identified an array...
Trypanosoma brucei is the causative agent of human sleeping sickness and animal trypanosomiasis in sub-Saharan Africa, it has been subdivided into three subspecies: gambiense rhodesiense, which cause humans, nonhuman infective brucei. T. b. most clinically relevant subspecies, being responsible for more than 90% all trypanosomal disease humans. The genome sequence now available, a Mendelian genetic system demonstrated brucei, facilitating analysis this diploid protozoan parasite. As an...
Human and animal African trypanosomiasis (HAT & AAT, respectively) remain a significant health economic issue across much of sub-Saharan Africa. Effective control AAT potential eradication HAT requires affordable, sensitive specific diagnostic tests that can be used in the field. Small RNAs blood or serum are attractive disease biomarkers due to their stability, accessibility available technologies for detection. Using RNAseq, we have identified trypanosome small RNA present at high levels...
Abstract In the skin, Trypanosoma brucei colonises subcutaneous white adipose tissue, and is proposed to be competent for forward transmission. The interaction between parasites, local immune system likely drive tissue wasting weight loss observed in cattle humans infected with T. . However, mechanistically, events leading are not fully understood. Here, using several complementary approaches, including mass cytometry by time of flight, bulk single cell transcriptomics, vivo genetic models,...
BackgroundAPOL1 variants G1 and G2 are common in populations with recent African ancestry. They associated protection from sleeping sickness, however homozygosity or compound heterozygosity for these is chronic kidney disease (CKD) related conditions. What not clear the extent of associations non-kidney-related disorders, whether there clusters diseases individual APOL1 genotypes.MethodsUsing a cohort 7462 UK Biobank participants ancestry, we conducted phenome-wide association study...
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...
In the mammalian host, biology of tissue-dwelling Trypanosoma brucei parasites is not completely understood, especially mechanisms involved in their extravascular colonization. The trypanosome flagellum an essential organelle multiple aspects parasites’ development. flagellar protein termed FLAgellar Member 8 (FLAM8) acts as a docking platform for pool cyclic AMP response 3 (CARP3) that signaling. FLAM8 exhibits stage-specific distribution suggesting specific functions and vector stages...
Human African trypanosomiasis has not been reported in Nigeria since 2012. Nevertheless, limitations of current surveillance programs mean that undetected infections may persist. We report a recent case stage 2 caused by Trypanosoma brucei gambiense acquired and imported into the United Kingdom.
Background Trypanosoma brucei is the causative agent of African Sleeping Sickness in humans and contributes to related veterinary disease, Nagana. T. segregated into three subspecies based on host specificity, geography pathology. b. limited animals (excluding some primates) throughout sub-Saharan Africa non-infective due trypanolytic factors found human serum. gambiense rhodesiense are infective sub-species. more prevalent human, causing over 97% cases. Study complicated that there two...
Myotonic dystrophy type 1 (DM1) is a rare genetic disorder, characterised by muscular dystrophy, myotonia, and other symptoms. DM1 caused the expansion of CTG repeat in 3'-untranslated region DMPK. Longer expansions are associated with greater symptom severity earlier age at onset. The primary mechanism pathogenesis thought to be mediated gain function CUG-containing RNA, that leads trans-dysregulation RNA metabolism many genes. Specifically, alternative splicing (AS) polyadenylation (APA)...
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...