A5082095695- Trypanosoma species research and implications
- Calcium signaling and nucleotide metabolism
- Toxoplasma gondii Research Studies
- Autophagy in Disease and Therapy
- Lysosomal Storage Disorders Research
- Genetic and Kidney Cyst Diseases
- Cellular transport and secretion
- Biochemical and Molecular Research
- Parasitic Infections and Diagnostics
- Research on Leishmaniasis Studies
- Cardiomyopathy and Myosin Studies
- Cytomegalovirus and herpesvirus research
- Pancreatic function and diabetes
- Galectins and Cancer Biology
- interferon and immune responses
- Bacteriophages and microbial interactions
- Microtubule and mitosis dynamics
- RNA Interference and Gene Delivery
- Heme Oxygenase-1 and Carbon Monoxide
- Characterization and Applications of Magnetic Nanoparticles
- Signaling Pathways in Disease
- HIV/AIDS drug development and treatment
- Peptidase Inhibition and Analysis
- Genomics and Phylogenetic Studies
- Plant responses to water stress
National University of Singapore
2014-2024
In-Q-Tel
2012
Yale University
2002-2009
Ludwig Cancer Research
2004-2007
Ludwig Cancer Research
2005
University of Pennsylvania
1998-2002
University of British Columbia
1999-2000
South University
1998
Segmentation of biological volumes is a crucial step needed to fully analyse their scientific content. Not having access convenient tools with which segment or annotate the data means many remain under-utilised. Automatic segmentation still very challenging research field, and current methods usually require large amount manually-produced training deliver high-quality segmentation. However, complex appearance cellular features high variance from one sample another, along time-consuming work...
We have engineered a mutant version of the green fluorescent protein GFP (Cormack et al. Selected for bright fluorescence in E. coli. Gene 1996;173:33–38) expression protozoan parasite Toxoplasma gondii. Although intact was not expressed at any detectable level, fusion proteins could be detected by microscopy, flow cytometry (FACS), and immunoblotting. Both extracellular tachyzoites T. gondii-infected host cells readily sorted FACS, which should facilitate variety selection strategies....
Duplication of the single Golgi apparatus in protozoan parasite Trypanosoma brucei has been followed by tagging a putative enzyme and matrix protein with variants GFP. Video microscopy shows that new appears de novo, near to old Golgi, about two hours into cell cycle grows over two-hour period until it is same size as Golgi. endoplasmic reticulum (ER) export site follows exactly time course. Photobleaching experiments show not exclusive product ER site. Rather, supplied, at least part,...
Centrins are highly conserved components of the centrosome, which in parasitic protozoan T. brucei comprises basal body and nucleates flagellum used for locomotion. Here, we found TbCentrin2 an additional bi-lobed structure near to Golgi apparatus. One lobe was associated with old Golgi, other became newly forming as cell grew. Depletion TbCentrin1 inhibited duplication body, whereas depletion also Golgi. Thus, a Centrin2-containing distinct from appears mark site new assembly.
By eliciting inflammatory responses, the human immunosurveillance system notably combats invading pathogens, during which acute phase proteins (CRP and cytokines) are elevated markedly. However, Pseudomonas aeruginosa is a persistent opportunistic pathogen prevalent at site of local inflammation, its acquisition multiple antibiotic-resistance factors poses grave challenges to patient healthcare management. Using blood samples from infected patients, we demonstrate that P. effectively killed...
Trypanosoma brucei, a flagellated protozoan parasite causing human sleeping sickness, relies on subpellicular microtubule array for maintenance of cell morphology. The flagellum is attached to the body through poorly understood attachment zone (FAZ), and regulates morphogenesis using an unknown mechanism. Here we identified new FAZ component, CC2D, which contains coiled-coil motifs followed by C-terminal C2 domain. T. brucei CC2D present filament, FAZ-juxtaposed ER membrane basal bodies....
Trypanosoma brucei is a parasitic protozoan that causes African sleeping sickness. It contains flagellum required for locomotion and viability. In addition to microtubular axoneme, the crystalline paraflagellar rod (PFR) connecting proteins. We show here, by cryoelectron tomography, structure of in three bending states. The PFR lattice straight flagella repeats every 56 nm along length matching spacing During flagellar bending, crystallographic unit cell lengths remain constant while...
Trypanosoma brucei, a unicellular parasite, contains several single-copied organelles that duplicate and segregate in highly coordinated fashion during the cell cycle. In procyclic stage, bi-lobed structure is found adjacent to single ER exit site Golgi apparatus, forming both stable dynamic association with other cytoskeletal components including basal bodies seed flagellum flagellar pocket collar critical for biogenesis. To further understand bi-lobe its organelles, we performed proteomic...
African trypanosomes have a single, membrane-bounded flagellum that is attached to the cell cortex by membrane adhesion proteins and an intracellular attachment zone (FAZ) complex. The coordinated assembly of FAZ, during cycle life development, plays pivotal role in organelle positioning, division morphogenesis. To understand how FAZ are coordinated, we examined domain organization protein 1 (FLA1), glycosylated, transmembrane essential for division. By immunoprecipitation FLA1-truncation...
ABSTRACT Adhesion of motile flagella to the cell body in Trypanosoma brucei requires a filamentous cytoskeletal structure termed flagellum attachment zone (FAZ). Despite its essentiality, complete molecular composition FAZ filament and roles assembly remain poorly understood. By localization-based screening, we here identified new protein, which called FAZ2. Knockdown FAZ2 disrupted filament, destabilized multiple proteins caused cytokinesis defect. We also showed that depletion another...
Pathogenic protists are a group of organisms responsible for causing variety human diseases including malaria, sleeping sickness, Chagas disease, leishmaniasis, and toxoplasmosis, among others. These diseases, which affect more than one billion people globally, mainly the poorest populations, characterized by severe chronic stages lack effective antiparasitic treatment. Parasitic display complex life-cycles go through different cellular transformations in order to adapt hosts they live in....
Apicomplexan species constitute a diverse group of parasitic protozoa, which are responsible for wide range diseases in many organisms. Despite differences the they cause, these parasites share an underlying biology, from genetic controls used to differentiate through complex parasite life cycle, basic biochemical pathways employed intracellular survival, distinctive cell biology necessary host attachment and invasion. Different lend themselves study different aspects biology: Eimeria...
A Golgi-associated bi-lobed structure was previously found to be important for Golgi duplication and cell division in Trypanosoma brucei. To further understand its functions, comparative proteomics performed on extracted flagellar complexes (including the flagellum flagellum-associated structures such as basal bodies bi-lobe) purified flagella identify new bi-lobe proteins. leucine-rich repeats containing protein, TbLRRP1, characterized a component. The anterior part of TbLRRP1-labeled is...
The early branching eukaryote Trypanosoma brucei contains functional autophagy machinery that allows regulated degradation of its own cellular components. In this study, we examined the function two Atg8 genes, TbAtg8.1 and TbAtg8.2, in starvation-induced autophagosome formation cell death procyclic T. brucei. Upon starvation, both TbAtg8.2 localize to punctate structures characteristic autophagosomes as shown by fluorescence electron microscopy, wortmannin chloroquine treatments. While...
Abstract Trypanosoma cruzi and brucei are parasites that cause Chagas disease African sleeping sickness, respectively. There is an urgent need for the development of new drugs against both diseases due to lack adequate cures emerging drug resistance. One promising strategy discovery small‐molecule therapeutics parasitic has been target major cysteine proteases such as cruzain T. , rhodesain/TbCatB . Azadipeptide nitriles belong a novel class extremely potent protease inhibitors papain‐like...
We report herein the design, synthesis and application of K11777-derived activity-based probes (ABPs) allowing in situ profiling identification potential cellular targets K11777 Trypanosoma brucei.
Lysosomes play important roles in autophagy, not only autophagosome degradation, but also autophagy initiation. In Trypanosoma brucei, an early divergent protozoan parasite, we discovered a previously unappreciated function of the acidocalcisome, lysosome-related organelle characterized by acidic pH and large content Ca(2+) polyphosphates, regulation. Starvation- chemical-induced is accompanied with acidocalcisome acidification, blocking acidification completely inhibits formation. Blocking...
The new Golgi in the protozoan parasite Trypanosoma brucei grows near to old and adjacent growing endoplasmic reticulum exit site. Growth is now shown be at least a two-stage process, which representative matrix marker (GRASP) enzyme (GntB) are delivered site of assembly, followed approximately 10 min later by COPI component (epsilon-COP) trans-Golgi network (TGN) (GRIP70). A secretory cargo (signal sequence-YFP) appeared early but did not enter until second stage. Together these data...
Centrins are Ca(2+)-binding proteins that have been implicated in a number of biological processes, including organelle duplication, mRNA export, DNA repair and signal transduction. In the protozoan parasite Trypanosoma brucei we previously described TbCentrin2, which is present on bi-lobed structure, involved duplication segregation Golgi complex. Recently, another centrin, TbCentrin4, was also found at bi-lobe has cytokinesis. We now show cytokinesis not inhibited, but dysregulation...
Autophagy is a catabolic cellular process required to maintain protein synthesis, energy production and other essential activities in starved cells. While the exact nutrient sensor(s) yet be identified, deprivation of amino acids, glucose, growth factor nutrients can serve as metabolic stimuli initiate autophagy higher eukaryotes. In early-branching unicellular parasite Trypanosoma brucei, which proliferate procyclic form (PCF) tsetse fly or bloodstream (BSF) animal hosts, robustly triggered...