A5047644295- Malaria Research and Control
- Trypanosoma species research and implications
- Mosquito-borne diseases and control
- Research on Leishmaniasis Studies
- Invertebrate Immune Response Mechanisms
- Computational Drug Discovery Methods
- Parasites and Host Interactions
- HIV/AIDS drug development and treatment
- Drug Transport and Resistance Mechanisms
- Toxoplasma gondii Research Studies
- HIV Research and Treatment
- Parasitic Infections and Diagnostics
- Signaling Pathways in Disease
- Helminth infection and control
- Parasite Biology and Host Interactions
- Biochemical and Molecular Research
- Erythrocyte Function and Pathophysiology
- Insect Resistance and Genetics
- Complement system in diseases
- Cancer-related Molecular Pathways
- Hemoglobinopathies and Related Disorders
- Protein Structure and Dynamics
- Animal Virus Infections Studies
- Microtubule and mitosis dynamics
- Multiple Myeloma Research and Treatments
RMIT University
2019-2025
MIT University
2021-2024
Roche (Switzerland)
2023-2024
RMIT Europe
2022
Burnet Institute
2022
National Institute of Mental Health and Neurosciences
2021
Monash University
2011-2020
Australian Regenerative Medicine Institute
2012-2020
Wellcome Centre for Molecular Parasitology
2005-2018
Discovery Institute
2018
The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb, www.guidetopharmacology.org) and its precursor IUPHAR-DB, have captured expert-curated interactions between targets ligands from selected papers in pharmacology drug discovery since 2003. This resource continues be developed conjunction with the International Union of Basic Clinical Pharmacology (IUPHAR) British Pharmacological Society (BPS). As previously described, our unique model content selection quality control is based on 96 target-class...
Abstract In single-cell analysis, cellular activity and parameters are assayed on an individual, rather than population-average basis. Essential to observing the of these cells over time is ability trap, pattern retain them, for which previous single-cell-patterning work has principally made use mechanical methods. While successful as a long-term cell-patterning strategy, devices remain essentially single use. Here we introduce new method patterning multiple spatially separated particles...
The role of protein phosphorylation in the life cycle malaria parasites is slowly emerging. Here we combine global phospho-proteomic analysis with kinome-wide reverse genetics to assess importance Plasmodium falciparum asexual proliferation. We identify 1177 sites on 650 parasite proteins that are involved a wide range general cellular activities such as DNA synthesis, transcription and metabolism well key processes invasion cyto-adherence. Several kinases themselves phosphorylated putative...
The eukaryotic phylum Apicomplexa encompasses thousands of obligate intracellular parasites humans and animals with immense socio-economic health impacts. We sequenced nuclear genomes Chromera velia Vitrella brassicaformis, free-living non-parasitic photosynthetic algae closely related to apicomplexans. Proteins from key metabolic pathways the endomembrane trafficking systems associated a lifestyle have been progressively non-randomly lost during adaptation parasitism. ancestor contained...
Global production of chickens has trebled in the past two decades and they are now most important source dietary animal protein worldwide. Chickens subject to many infectious diseases that reduce their performance productivity. Coccidiosis, caused by apicomplexan protozoa genus Eimeria , is one poultry diseases. Understanding biology parasites underpins development new drugs vaccines needed improve global food security. We have produced annotated genome sequences all seven species infect...
Abstract Our understanding of the key phosphorylation-dependent signalling pathways in human malaria parasite, Plasmodium falciparum , remains rudimentary. Here we address this issue for essential cGMP-dependent protein kinase, PfPKG. By employing chemical and genetic tools combination with quantitative global phosphoproteomics, identify phosphorylation sites on 69 proteins that are direct or indirect cellular targets These PfPKG include involved cell signalling, proteolysis, gene...
Cyclin-dependent kinases trigger and coordinate transitions between different phases the cell division cycle (CDK1, 2, 3, 4, 6, 7). They also play a role in apoptosis (CDK2), neuronal cells (CDK5) control of transcription (CDK 7, 8, 9). Intensive screening has lead to recent identification series chemical inhibitors CDKs: olomoucine, roscovitine, purvalanol, CVT-313, flavopiridol, g-butyrolactone, indirubins, paullones staurosporine. Some these compounds display remarkable selectivities...
During asexual intraerythrocytic development, Plasmodium falciparum diverges from the paradigm of eukaryotic cell cycles by undergoing multiple rounds DNA replication and nuclear division without cytokinesis. A better understanding molecular switches that coordinate a myriad events for progression parasite through developmental stages will be fundamental importance rational design intervention strategies. To achieve this goal, we performed isobaric tag-based quantitative proteomics...
The human malaria parasite Plasmodium falciparum is auxotrophic for most amino acids. Its acid needs are met largely through the degradation of host erythrocyte hemoglobin; however must acquire isoleucine exogenously, because this not present in adult hemoglobin. We report that when withdrawn from culture medium intraerythrocytic P. falciparum, slows its metabolism and progresses developmental cycle at a reduced rate. Isoleucine-starved parasites remain viable 72 h resume rapid growth upon...
Sporozoites, the invasive form of malaria parasites transmitted by mosquitoes, are quiescent while in insect salivary glands. Sporozoites only differentiate inside hepatocytes mammalian host. We show that sporozoite latency is an active process controlled a eukaryotic initiation factor-2α (eIF2α) kinase (IK2) and phosphatase. IK2 activity dominant gland sporozoites, leading to inhibition translation accumulation stalled mRNAs into granules. When sporozoites injected host, eIF2α phosphatase...
Atomic force microscopy-infrared (AFM-IR) spectroscopy is a powerful new technique that can be applied to study molecular composition of cells and tissues at the nanoscale. AFM-IR maps are acquired using single wavenumber value: they show either absorbance plotted against value or ratio two values. Here, we implement multivariate image analysis generate use this approach resolve subcellular structural information in red blood infected with Plasmodium falciparum different stages development....
The search for antimalarial chemotypes with modes of action unrelated to existing drugs has intensified the recent failure first-line therapies across Southeast Asia. Here, we show that trisubstituted imidazole MMV030084 potently inhibits hepatocyte invasion by Plasmodium sporozoites, merozoite egress from asexual blood stage schizonts, and male gamete exflagellation. Metabolomic, phosphoproteomic, chemoproteomic studies, validated conditional knockdown parasites, molecular docking,...
The molecular mechanisms regulating the sexual development of malaria parasites from gametocytes to oocysts in their mosquito vector are still largely unexplored. In other eukaryotes, NIMA-related kinases (Neks) regulate cell cycle progression and have been implicated regulation meiosis. Here, we demonstrate that Nek-4, a new Plasmodium member Nek family, is essential for completion parasite. Recombinant falciparum Nek-4 possesses protein kinase activity displays substrate preferences...
The genome of the human parvovirus B19 contains a transcriptional promoter (BP06) at map position 6, upstream from nonstructural protein genes. By cotransfecting HeLa cells with this cloned before chloramphenicol acetyltransferase (CAT) gene together plasmid containing almost whole genome, we showed that BP06 is transactivated by product. transactivating viral was identified as NS-1. NS-1 synthesized in wheat germ extract specifically stimulates transcription vitro. minute virus mice (MVM)...
Summary The transmission of malaria parasites to the mosquito depends critically on rapid initiation sexual reproduction in response triggers from midgut environment. We here identify an essential function for atypical mitogen‐activated protein kinase rodent parasite Plasmodium berghei , Pbmap‐2, male differentiation and mosquito. A deletion mutant no longer expressing Pbmap‐2 develops as wild type throughout asexual erythrocytic phase life cycle. Gametocytes, stages, form normally respond...
Summary Processes at the surface of Plasmodium falciparum ‐infected erythrocytes such as antigenic variation and cytoadhesion may be modulated by active signalling between host parasite. Potential candidates for this role include putative kinases FIKK family. The novel Apicomplexa ‐specific gene has expanded in P. to 20 sequence‐related members distributed 11 chromosomes. Specific antibodies raised against different indicated that most proteins locate punctate foci erythrocyte cytoplasm...
The kinome of the human malaria parasite Plasmodium falciparum includes two genes encoding mitogen-activated protein kinase (MAPK) homologues, pfmap-1 and pfmap-2, but no clear orthologue MAPK (MAPKK) family, raising question mode activation function plasmodial MAPKs. Functional studies in rodent model berghei recently showed map-2 gene to be dispensable for asexual growth gametocytogenesis, essential male gametogenesis mosquito vector. Here, we demonstrate by using a reverse genetics...