A5035168949- Malaria Research and Control
- Mosquito-borne diseases and control
- Invertebrate Immune Response Mechanisms
- Trypanosoma species research and implications
- Vector-borne infectious diseases
- Research on Leishmaniasis Studies
- Complement system in diseases
- Drug Transport and Resistance Mechanisms
- Aquaculture disease management and microbiota
- Microbial infections and disease research
- HIV Research and Treatment
- Parasite Biology and Host Interactions
- Erythrocyte Function and Pathophysiology
- Bacteriophages and microbial interactions
- Chromosomal and Genetic Variations
- vaccines and immunoinformatics approaches
- Parasites and Host Interactions
- Insect Resistance and Genetics
- Computational Drug Discovery Methods
- Biosensors and Analytical Detection
- Nuclear Structure and Function
- CRISPR and Genetic Engineering
- Multiple Myeloma Research and Treatments
- Sperm and Testicular Function
- Toxoplasma gondii Research Studies
Istituto Superiore di Sanità
2015-2024
Weatherford College
2007
In-Q-Tel
2007
Imperial College London
1995
University of Edinburgh
1989-1995
Centre National de la Recherche Scientifique
1992
Institut Pasteur
1992
Institute of Genetics and Cancer
1990
University of London
1990
London School of Hygiene & Tropical Medicine
1990
A major cause of the paucity new starting points for drug discovery is lack interaction between academia and industry. Much global resource in biology present universities, whereas focus medicinal chemistry still largely within Open source discovery, with sharing information, clearly a first step towards overcoming this gap. But interface could especially be bridged through scale-up open physical compounds, which would accelerate finding discovery. The Medicines Malaria Venture Box...
Sexual stages of the human malaria parasite Plasmodium falciparum use hematopoietic system bone marrow as a developmental niche.
Despite over a century of study malaria parasites, parts the Plasmodium falciparum life cycle remain virtually unknown. One these is early gametocyte stage, round shaped cell morphologically similar to an asexual trophozoite in which major cellular transformations ensure subsequent development elongated gametocyte. We developed protocol obtain for first time highly purified preparations gametocytes using transgenic line expressing green fluorescent protein from onset gametocytogenesis....
SUMMARY Blood-stage malaria parasites in the vertebrate host can develop either into asexual, multiplying forms, called schizonts, or gametocytes, sexual stages of parasite. In present work we studied differentiation asexual gametocytes progeny single, isolated schizonts clone 3D7A Plasinodium falciparum , using monoclonal antibodies specific for We observed that obtained from a continuous culture undergoing serial cycles growth and dilution with fresh red blood cells produced only...
The asexual blood stages of Plasmodium falciparum cause the most lethal form human malaria. During growth within an infected red cell, parasite multiplication and formation invasive merozoites is called schizogony. Here, we present a detailed analysis phosphoproteome P. schizonts revealing 2541 unique phosphorylation sites, including 871 novel sites. Prominent roles for cAMP-dependent protein kinase A- phosphatidylinositol-signaling were identified following by functional enrichment,...
Primaquine (PQ) is an essential antimalarial drug but despite being developed over 70 years ago, its mode of action unclear. Here, we demonstrate that hydroxylated-PQ metabolites (OH-PQm) are responsible for efficacy against liver and sexual transmission stages Plasmodium falciparum. The activity PQ depends on host CYP2D6 status, whilst OH-PQm display direct, CYP2D6-independent, activity. requires hepatic metabolism to exert gametocyte stages. modest parasite gametocytes; however, potency...
Plasmodium gametocytes, responsible for malaria parasite transmission from humans to mosquitoes, represent a crucial target new antimalarial drugs achieve elimination/eradication. We developed novel colorimetric screening method anti-gametocyte compounds based on the lactate dehydrogenase (pLDH) assay, already standardized asexual stages, measure gametocyte viability and drug susceptibility. Gametocytogenesis of 3D7 NF54 falciparum strains was induced in vitro parasites were depleted with...
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,...
Malaria parasites invade erythrocytes of their host both for asexual multiplication and differentiation to male female gametocytes - the precursor cells Plasmodium gametes. For further development parasite is dependent on efficient release daughter gametes from erythrocyte. How malarial exit remains largely unknown. We here report characterization a berghei protein that involved in egress Protein MDV-1/PEG3, like its falciparum orthologue, present sexes, but more abundant female, where it...
In Plasmodium falciparum infections the parasite transmission stages, gametocytes, mature in 10 days sequestered internal organs. Recent studies suggest that cell mechanical properties rather than adhesive interactions play a role sequestration during gametocyte maturation. It remains instead obscure how is established, and earliest sexual morphologically similar to asexual trophozoites, modify infected erythrocytes their cytoadhesive at onset of gametocytogenesis. Here, purified P. early...
Surface-associated TRAP (thrombospondin-related anonymous protein) family proteins are conserved across the phylum of apicomplexan parasites. thought to play an integral role in parasite motility and cell invasion by linking extracellular environment with submembrane actomyosin motor. Blood stage forms malaria Plasmodium express a protein called merozoite-TRAP (MTRAP) that has been implicated erythrocyte invasion. Using MTRAP-deficient mutants rodent-infecting P. berghei human-infecting...
Summary Emerging resistance to first‐line antimalarial combination therapies threatens malaria treatment and the global elimination campaign. Improved therapeutic strategies are required protect existing drugs enhance efficacy. We report that piperazine‐containing compound ACT‐451840 exhibits single‐digit nanomolar inhibition of Plasmodium falciparum asexual blood stages transmissible gametocyte forms. Genome sequence analyses in vitro ‐derived ACT‐451840‐resistant parasites revealed single...
We have cloned Pfnek-1, a gene encoding novel protein kinase from the human malaria parasite Plasmodium falciparum. This enzyme displays maximal homology to never-in-mitosis/Aspergillus (NIMA)/NIMA-like (Nek) family of kinases, whose members are involved in eukaryotic cell division processes. Similar other P. falciparum kinases and many enzymes NIMA/Nek family, Pfnek-1 possesses large C-terminal extension addition catalytic domain. Bacterially expressed recombinant is able autophosphorylate...
Commitment to the production of female and male gametocytes was studied in NF54 line human malaria parasite Plasmodium falciparum . The development sibling parasites derived from individual schizonts followed, 2 antisera against gametocyte-specific protein Pfg377 α-tubulin II were used determine sex gametocytes. experiment showed that cohorts stained a mutually exclusive fashion by only one or other antiserum, indicating committed yield sexual progeny produce same sex. This work suggests P....
The cDNA encoding Pfmap-2, an enzyme of the human malaria parasite Plasmodium falciparum, was cloned, sequenced, and expressed in Escherichia coli. open reading frame carried by Pfmap-2 encodes a 508-amino acid polypeptide 59.2 kDa with maximal homology to mitogen-activated protein kinases (MAPKs) from various organisms. purified recombinant displayed functional characteristics MAPKs such as (i) ability undergo autophosphorylation, (ii) phosphorylate myelin basic protein, classical MAPK...
Summary Two members of the mitogen‐activated protein kinase (MAPK) family have been previously characterized in Plasmodium falciparum , but vitro attempts at identifying MAP (MAPKK) homologues failed. Here we report characterization a novel plasmodial kinase, PfPK7, whose top scores blastp analysis belong to MAPKK3/6 subgroup MAPKKs. However, homology MAPKKs is restricted regions C‐terminal lobe domain, whereas N‐terminal region closer fungal A enzymes (PKA, AGC group kinases). Hence, PfPK7...
Since the development of methods for in vitro cultivation asexual blood stages P.faZciparum (1) and production mature gametocytes from such cultures capable infecting mosquitoes (2), it has been possible to conduct a wide range studies on sexual P. filciparum. These include infectivity this parasite (3) biology parasites vector (4) including transmission blocking immunity using monoclonal antibodies against gamete surface antigens (5) human sera following natural malarial infections (6). The...
Summary Osmiophilic bodies are membrane‐bound vesicles, found predominantly in Plasmodium female gametocytes, that become progressively more abundant as the gametocyte reaches full maturity. These vesicles lie beneath subpellicular membrane of gametocyte, and release their contents into parasitophorous vacuole has been postulated to aid escape gametocytes from erythrocyte after ingestion by mosquito. Currently, only protein known be associated with osmiophilic falciparum is Pfg377, a...