A5016049967- Malaria Research and Control
- Mosquito-borne diseases and control
- Trypanosoma species research and implications
- Drug Transport and Resistance Mechanisms
- HIV Research and Treatment
- Toxoplasma gondii Research Studies
- Research on Leishmaniasis Studies
- Lipid Membrane Structure and Behavior
- Parasites and Host Interactions
- Invertebrate Immune Response Mechanisms
- Sphingolipid Metabolism and Signaling
- IL-33, ST2, and ILC Pathways
- Microbial Metabolic Engineering and Bioproduction
- Trace Elements in Health
- Inhalation and Respiratory Drug Delivery
- Insect symbiosis and bacterial influences
- Complement system in diseases
- Poisoning and overdose treatments
- Biochemical and Molecular Research
- Insect Pest Control Strategies
- Immune cells in cancer
- Autophagy in Disease and Therapy
- Vector-borne infectious diseases
- Pesticide Exposure and Toxicity
- Hemoglobinopathies and Related Disorders
Bernhard Nocht Institute for Tropical Medicine
2013-2023
Centre for Structural Systems Biology
2019-2023
Universität Hamburg
2019-2023
University of Bern
2013-2020
Humboldt-Universität zu Berlin
2015
Institute of Cell Biology
2013
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 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...
Abstract Immunomodulation is a common feature of chronic helminth infections and mainly attributed to the secretion bioactive molecules, which target modify host immune cells. In this study, we show that immunomodulator AvCystatin, cysteine protease inhibitor, induces novel regulatory macrophage (Mreg; AvCystatin-Mreg), sufficient mitigate major parameters allergic airway inflammation colitis in mice. A single adoptive transfer AvCystatin-Mreg before allergen challenge suppressed...
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...
During their development within the vertebrate host, Plasmodium parasites infect hepatocytes and red blood cells. Within these cells, are surrounded by a parasitophorous vacuole membrane (PVM). The PVM plays an essential role for interaction of with host cells; however, only limited number proteins this have been identified so far. This is partially because systematic proteomic analysis protein content has difficult in past, due to difficulties encountered attempts separate from other...
ABSTRACT A crucial step in the life cycle of Plasmodium parasites is transition from liver stage to blood stage. Hepatocyte-derived merozoites reach vessels inside host cell-derived vesicles called merosomes. The molecular basis merosome formation only partially understood. Here we show that berghei merozoites, upon rupture parasitophorous vacuole membrane, destabilize cell membrane (HCM) and induce separation actin cytoskeleton HCM. At same time, phospholipid protein composition HCM appears...
Proteins of the lipocalin family are known to bind small hydrophobic ligands and involved in various physiological processes ranging from lipid transport oxidative stress responses. The genome malaria parasite Plasmodium falciparum contains a single protein PF3D7_0925900 with signature. Using crystallography small-angle X-ray scattering, we show that has tetrameric structure typical monomers; hence name it P. (PfLCN). We PfLCN is expressed intraerythrocytic stages localizes parasitophorous...
The inner membrane complex (IMC) is a defining feature of apicomplexan parasites, which confers stability and shape to the cell, functions as scaffolding compartment during formation daughter cells plays an important role in motility invasion different life cycle stages these single-celled organisms. To explore IMC proteome malaria parasite Plasmodium falciparum we applied proximity-dependent biotin identification (BioID)-based proteomics approach, using established marker protein...
S-adenosylmethionine synthetase (SAMS) is a key enzyme for the synthesis of lone methyl donor S-adenosyl methionine (SAM), which involved in transmethylation reactions and hence required cellular processes such as DNA, RNA, histone methylation, but also polyamine biosynthesis proteostasis. In human malaria parasite
Malaria parasite release (egress) from host red blood cells involves parasite-mediated membrane poration and rupture, thought to involve membrane-lytic effector molecules such as perforin-like proteins and/or phospholipases. With the aim of identifying these effectors, we disrupted expression two Plasmodium falciparum simultaneously showed that they have no essential roles during stage egress. Proteomic profiling discharged into parasitophorous vacuole (PV) just prior egress detected...
During asexual replication within the Anopheles mosquito and their vertebrate host, Plasmodium parasites depend on generation of a massive amount new plasma membrane to produce thousands daughter parasites. How parasite (PPM) is formed has mostly been studied by electron microscopy, which does not allow an insight into dynamics this process. We generated berghei reporter line GFP-tagging non-essential PPM-localized protein, followed development in living through entire life cycle. By...
Summary To fuel the tremendously fast replication of Plasmodium liver stage parasites, endoplasmic reticulum (ER) must play a critical role as major site protein and lipid biosynthesis. In this study, we analysed parasite's ER morphology function. Previous studies exploring parasite have mainly focused on blood stage. Visualizing berghei during development, found that forms an interconnected network throughout with perinuclear peripheral localizations. Surprisingly, observed additionally...
The malaria parasite
Plasmodium parasites express a potent inhibitor of cysteine proteases (ICP) throughout their life cycle. To analyze the role ICP in different cycle stages, we generated stage-specific knockout berghei (PbICP). Excision pbicb gene occurred infective sporozoites and resulted impaired sporozoite invasion hepatocytes, despite residual PbICP protein being detectable sporozoites. The vast majority these invading cultured hepatocyte cell line did not develop to mature liver but few that...
ABSTRACT For its replication within red blood cells, the malaria parasite depends on a highly active and regulated lipid metabolism. Enzymes involved in metabolic processes such as phospholipases are, therefore, potential drug targets. Here, using reverse genetics approaches, we show that only 1 out of 19 putative expressed asexual stages Plasmodium falciparum is essential for proliferation vitro , pointing toward high level redundancy among members this enzyme family. Using conditional...
Transmission of malaria parasites to the mosquito is mediated by sexual precursor cells, gametocytes. Upon entering midgut, gametocytes egress from enveloping erythrocyte while passing through gametogenesis. Egress follows an inside-out mode during which membrane parasitophorous vacuole (PV) ruptures prior membrane. Membrane rupture requires exocytosis specialized vesicles parasites; that is, osmiophilic bodies (OBs) involved in rupturing PV membrane, and harbor perforin-like protein PPLP2...
During the symptomatic human blood phase, malaria parasites replicate within red cells. Parasite proliferation relies on uptake of nutrients, such as amino acids, from host cell and plasma, requiring transport across multiple membranes. Amino acids are delivered to parasite through parasite-surrounding vacuolar compartment by specialized nutrient-permeable channels erythrocyte membrane parasitophorous vacuole (PVM). However, further plasma (PPM) is currently not well characterized. In this...
The evolution of insecticide resistance threatens current malaria control methods, which rely heavily on chemical insecticides. magnitude the threat will be determined by phenotypic expression in those mosquitoes that can transmit malaria. These differ from majority mosquito population two main ways; they carry sporozoites (the infectious stage Plasmodium parasite) and are relatively old, as need to survive development period parasite. This study examines effects infection berghei age...
For their proliferation within red blood cells, malaria parasites depend on a functional electron transport chain (ETC) mitochondrion, which is the target of several antimalarial drugs. Here, we have used gene disruption to identify patatin-like phospholipase,
Mitogen-activated protein kinases (MAPKs) regulate key signaling events in eukaryotic cells. In the genomes of protozoan Plasmodium parasites, causative agents malaria, two genes encoding with significant homology to other MAPKs have been identified (mapk1, mapk2). this work, we show that both are transcribed during berghei liver stage development, and analyze expression subcellular localization PbMAPK1 parasites. Live cell imaging transgenic parasites expressing GFP-tagged revealed a...
Malaria research is greatly dependent on and has drastically advanced with the possibility of genetically modifying Plasmodium parasites. The commonly used transfection protocol by Janse colleagues utilizes blood stage-derived berghei schizonts that have been purified from a culture density gradient centrifugation. Naturally, this depends availability suitably infected mice, constituting time-based variable. In study, potential transfecting liver merozoites was explored. cell culture, upon...
Transmission of malaria parasites to the mosquito is mediated by sexual precursor cells, gametocytes. Upon entering midgut, gametocytes egress from enveloping erythrocyte while passing through gametogenesis. Egress follows an inside-out mode during which membrane parasitophorous vacuole ruptures prior membrane. Membrane rupture requires exocytosis specialized secretory vesicles parasites; i.e. osmiophilic bodies (OBs) involved in rupturing membrane, and (here termed g-exonemes) that harbour...