A5023745071- Malaria Research and Control
- Mosquito-borne diseases and control
- Autophagy in Disease and Therapy
- Vector-borne infectious diseases
- Parasites and Host Interactions
- Drug Transport and Resistance Mechanisms
- Toxoplasma gondii Research Studies
- Research on Leishmaniasis Studies
- Toxin Mechanisms and Immunotoxins
- Invertebrate Immune Response Mechanisms
- Immune Cell Function and Interaction
- HIV Research and Treatment
- Hepatitis B Virus Studies
- Vibrio bacteria research studies
- Vector-Borne Animal Diseases
- Parasite Biology and Host Interactions
- Trypanosoma species research and implications
- Complement system in diseases
- NF-κB Signaling Pathways
- Parasitic Infections and Diagnostics
- Computational Drug Discovery Methods
- Coccidia and coccidiosis research
- Helminth infection and control
- Aquaculture disease management and microbiota
- T-cell and Retrovirus Studies
University of Bern
2016-2025
Bernhard Nocht Institute for Tropical Medicine
2006-2020
Institute of Cell Biology
2013-2019
Institut Pasteur
2006
Universidade Federal de São Paulo
2006
Universität Hamburg
2004-2006
University Medical Center Hamburg-Eppendorf
2005-2006
Radboud University Medical Center
2005
Leiden University Medical Center
2005
Radboud University Nijmegen
2005
The merozoite stage of the malaria parasite that infects erythrocytes and causes symptoms disease is initially formed inside host hepatocytes. However, mechanism by which hepatic merozoites reach blood vessels (sinusoids) in liver escape immune system before invading remains unknown. Here, we show parasites induce death detachment their hepatocytes, followed budding parasite-filled vesicles (merosomes) into sinusoid lumen. Parasites simultaneously inhibit exposure phosphatidylserine on outer...
Immunization with Plasmodium sporozoites that have been attenuated by gamma-irradiation or specific genetic modification can induce protective immunity against subsequent malaria infection. The mechanism of protection is only known for radiation-attenuated sporozoites, involving cell-mediated and humoral immune responses invoked infected hepatocytes cells contain long-lived, partially developed parasites. Here we analyzed berghei are deficient in P36p (p36p(-)), a member the P48/45 family...
Regulated exocytosis by secretory organelles is important for malaria parasite invasion and egress. Many effector proteins, including perforins, adhesins, proteases, are extensively proteolytically processed both pre- postexocytosis. Here we report the multistage antiplasmodial activity of aspartic protease inhibitor hydroxyl-ethyl-amine-based scaffold compound 49c. This inhibits preexocytosis processing several secreted rhoptry microneme proteins targeting corresponding maturases...
Plasmodium parasites are transmitted by Anopheles mosquitoes to the mammalian host and actively infect hepatocytes after passive transport in bloodstream liver. In their target hepatocyte, reside within a parasitophorous vacuole (PV). present study it was shown that membrane (PVM) can be targeted autophagy marker proteins LC3, ubiquitin, SQSTM1/p62 as well lysosomes process resembling selective autophagy. The dynamics of individual berghei-infected were followed live imaging throughout...
Plasmodium gene functions in mosquito and liver stages remain poorly characterized due to limitations the throughput of phenotyping at these stages. To fill this gap, we followed more than 1,300 barcoded P. berghei mutants through life cycle. We discover 461 genes required for efficient parasite transmission mosquitoes stage back into bloodstream mice. analyze screen context genomic, transcriptomic, metabolomic data by building a thermodynamic model liver-stage metabolism, which shows major...
The inner membrane complex (IMC) is a unifying morphological feature of all alveolate organisms. It consists flattened vesicles underlying the plasma and interconnected with cytoskeleton. Depending on ecological niche organisms, function IMC ranges from fundamental role as reinforcement system to more specialized roles in motility cytokinesis. In this article, we present comprehensive evolutionary analysis components, which exemplifies adaptive nature IMCs' protein composition. Focusing...
The coordinated exit of intracellular pathogens from host cells is a process critical to the success and spread an infection. While phospholipases have been shown play important roles in bacteria cell egress virulence, their role release eukaryotic parasites largely unknown. We examined malaria parasite protein with phospholipase activity found it be involved hepatocyte egress. In hepatocytes, Plasmodium are surrounded by parasitophorous vacuole membrane (PVM), which must disrupted before...
Summary Plasmodium berghei is the causative agent of rodent malaria and widely used as a model system to study liver stage parasites. The entry P. sporozoites into hepatocytes has extensively been studied, but little known about parasite–host interaction during later developmental stages intracellular parasite. Growth parasite far beyond normal size host cell an important stress factor for infected cell. Cell trigger programmed death (apoptosis) we examined several apoptotic markers in...
Parasites have evolved a plethora of mechanisms to ensure their propagation and evade antagonistic host responses. The intracellular protozoan parasite Theileria is the only eukaryote known induce uncontrolled cell proliferation. Survival Theileria-transformed leukocytes depends strictly on constitutive nuclear factor kappa B (NF-kappaB) activity. We found that this was mediated by recruitment multisubunit IkappaB kinase (IKK) into large, activated foci surface. IKK signalosome assembly...
Different features of sensorimotor function and behaviour were studied in murine cerebral malaria (CM) without involvement (non‐CM) applying the primary screen SHIRPA protocol. Histopathological analysis distinct brain regions was performed relative size haemorrhages plugging blood cells to vasculature analysed. Animals suffering from CM develop a wide range behavioural functional alterations progressive course disease with statistically significant impairment all categories assessed 36 h...
The protozoan parasite Plasmodium is transmitted by female Anopheles mosquitoes and undergoes obligatory development within a parasitophorous vacuole in hepatocytes before it released into the bloodstream. transition to blood stage was previously shown involve packaging of exoerythrocytic merozoites membrane-surrounded vesicles, called merosomes, which are delivered directly liver sinusoids. However, unclear whether membrane these merosomes derived from membrane, or host cell membrane. This...
In vivo visualization of Plasmodium parasites reveals sublocalization, deformability, and mobility gametocytes in the bone marrow.
Abstract Sequestration of red blood cells infected with the human malaria parasite Plasmodium falciparum in organs such as brain is considered important for pathogenicity. A similar phenomenon has been observed mouse models malaria, using rodent berghei , but it unclear whether P. proteins known to be involved this process are conserved parasite. Here we identify orthologues two key factors SBP1 and MAHRP1. Red parasites lacking or MAHRP1a fail bind endothelial receptor CD36 show reduced...
Analyzing molecular determinants of Plasmodium parasite cell death is a promising approach for exploring new avenues in the fight against malaria. Three major forms (apoptosis, necrosis and autophagic death) have been described multicellular organisms but which processes exist protozoa still matter debate. Here we suggest that all three types occur liver-stage parasites. Whereas typical markers apoptosis not found genome parasites, identified genes coding putative autophagy-marker proteins...
Bioluminescence imaging is widely used for cell-based assays and animal studies, both in biomedical research drug development. Its main advantages include its high-throughput applicability, affordability, high sensitivity, operational simplicity, quantitative outputs. In malaria research, bioluminescence has been discovery vivo vitro, exploring host-pathogen interactions, studying multiple aspects of Plasmodium biology. While the number fluorescent proteins available undergone a great...
The Plasmodium parasite, during its life cycle, undergoes three phases of asexual reproduction, these being repeated rounds erythrocytic schizogony, sporogony within oocysts on the mosquito midgut wall and exo-erythrocytic schizogony hepatocyte. During each phase parasite must ensure that every new daughter cell contains an apicoplast, as this organelle cannot be formed de novo is essential for survival. To date, studies visualizing apicoplast in live parasites have been restricted to blood...
Merozoites of malaria parasites invade red blood cells (RBCs), where they multiply by schizogony, undergoing development through ring, trophozoite and schizont stages that are responsible for pathogenesis. Here, we report a protein kinase-mediated signalling pathway involving host RBC PAK1 MEK1, which do not have orthologues in the Plasmodium kinome, is selectively stimulated falciparum-infected (versus uninfected) RBCs, as determined use phospho-specific antibodies directed against...
The liver stage of the Plasmodium parasite remains one most promising targets for intervention against malaria as it is clinically silent, precedes symptomatic blood and represents a bottleneck in life cycle. However, many aspects development during this are far from understood. During stage, undergoes extensive replication, forming tens thousands infectious merozoites each invading sporozoite. This implies very efficient accurate process cytokinesis thus also organelle segregation. We have...