Prof. Dr. Kai Matuschewski
Profil
Forschungsthemen7
GRK 2046/1: Parasiteninfektionen: Von experimentellen Modellen zu natürlichen Systemen (TP B01)
Quelle ↗Förderer: DFG Graduiertenkolleg Zeitraum: 05/2018 - 09/2019 Projektleitung: Prof. Dr. Kai Matuschewski
GRK 2046/2: Parasiteninfektionen: Von experimentellen Modellen zu natürlichen Systemen
Quelle ↗Förderer: DFG Graduiertenkolleg Zeitraum: 10/2019 - 03/2024 Projektleitung: Prof. Dr. Kai Matuschewski
GRK 2046/2: Parasiteninfektionen: Von experimentellen Modellen zu natürlichen Systemen (TP B01)
Quelle ↗Förderer: DFG Graduiertenkolleg Zeitraum: 10/2019 - 06/2024 Projektleitung: Prof. Dr. Kai Matuschewski
GRK 2046: Parasite Infections: From Experimental Models to Natural Systems
Quelle ↗Förderer: DFG Graduiertenkolleg Zeitraum: 04/2015 - 06/2024 Projektleitung: PD Dr. rer. nat. Susanne Hartmann
IGRK 2290/1: Grenzen überwinden: Molekulare Interaktionen bei Malaria
Quelle ↗Förderer: DFG Graduiertenkolleg Zeitraum: 09/2017 - 02/2022 Projektleitung: Prof. Dr. Kai Matuschewski
IGRK 2290: Grenzen überwinden: Molekulare Interaktionen bei Malaria
Quelle ↗Förderer: DFG Graduiertenkolleg Zeitraum: 09/2017 - 02/2024 Projektleitung: Prof. Dr. Kai Matuschewski
TWAS Malaria
Quelle ↗Förderer: DFG sonstige Programme Zeitraum: 07/2017 - 09/2017 Projektleitung: Prof. Dr. Kai Matuschewski
Mögliche Industrie-Partner10
Stand: 26.4.2026, 19:48:44 (Top-K=20, Min-Cosine=0.4)
- DYnamic control in hybrid plasmonic NAnopores: road to next generation multiplexed single MOlecule detectionP55.6%
- DYnamic control in hybrid plasmonic NAnopores: road to next generation multiplexed single MOlecule detection
- 8 Treffer55.3%
- Zuwendung im Rahmen des Programms „exist – Existenzgründungen aus der Wissenschaft“ aus dem Bundeshaushalt, Einzelplan 09, Kapitel 02, Titel 68607, Haushaltsjahr 2026, sowie aus Mitteln des Europäischen Strukturfonds (hier Euro-päischer Sozialfonds Plus – ESF Plus) Förderperiode 2021-2027 – Kofinanzierung für das Vorhaben: „exist Women“T55.3%
- Zuwendung im Rahmen des Programms „exist – Existenzgründungen aus der Wissenschaft“ aus dem Bundeshaushalt, Einzelplan 09, Kapitel 02, Titel 68607, Haushaltsjahr 2026, sowie aus Mitteln des Europäischen Strukturfonds (hier Euro-päischer Sozialfonds Plus – ESF Plus) Förderperiode 2021-2027 – Kofinanzierung für das Vorhaben: „exist Women“
- 53 Treffer53.9%
- Engineering of New-Generation Protein Secretion SystemsP53.9%
- Engineering of New-Generation Protein Secretion Systems
- 53 Treffer53.9%
- Engineering of New-Generation Protein Secretion SystemsP53.9%
- Engineering of New-Generation Protein Secretion Systems
- 53 Treffer53.9%
- Engineering of New-Generation Protein Secretion SystemsP53.9%
- Engineering of New-Generation Protein Secretion Systems
- 53 Treffer53.0%
- EU: Printed Logic for Applications of Screen Matrix Activation (PLASMAS)P53.0%
- EU: Printed Logic for Applications of Screen Matrix Activation (PLASMAS)
- 52 Treffer53.0%
- EU: Printed Logic for Applications of Screen Matrix Activation (PLASMAS)P53.0%
- EU: Printed Logic for Applications of Screen Matrix Activation (PLASMAS)
- 53 Treffer53.0%
- EU: Printed Logic for Applications of Screen Matrix Activation (PLASMAS)P53.0%
- EU: Printed Logic for Applications of Screen Matrix Activation (PLASMAS)
- 53 Treffer53.0%
- EU: Printed Logic for Applications of Screen Matrix Activation (PLASMAS)P53.0%
- EU: Printed Logic for Applications of Screen Matrix Activation (PLASMAS)
- 52 Treffer53.0%
- EU: Printed Logic for Applications of Screen Matrix Activation (PLASMAS)P53.0%
- EU: Printed Logic for Applications of Screen Matrix Activation (PLASMAS)
Publikationen25
Top 25 nach Zitationen — Quelle: OpenAlex (BAAI/bge-m3 embedded für Matching).
Cell · 565 Zitationen · DOI
Nature · 496 Zitationen · DOI
Molecular and Biochemical Parasitology · 454 Zitationen · DOI
Proceedings of the National Academy of Sciences · 414 Zitationen · DOI
Plasmodium parasites of mammals, including the species that cause malaria in humans, infect the liver first and develop there into clinically silent liver stages. Liver stages grow and ultimately produce thousands of first-generation merozoites, which initiate the erythrocytic cycles causing malaria pathology. Here, we present a Plasmodium protein with a critical function for complete liver stage development. UIS4 (up-regulated in infective sporozoites gene 4) is expressed exclusively in infective sporozoites and developing liver stages, where it localizes to the parasitophorous vacuole membrane. Targeted gene disruption of UIS4 in the rodent model malaria parasite Plasmodium berghei generated knockout parasites that progress through the malaria life cycle until after hepatocyte invasion but are severely impaired in further liver stage development. Immunization with UIS4 knockout sporozoites completely protects mice against subsequent infectious WT sporozoite challenge. Genetically attenuated liver stages may thus induce immune responses, which inhibit subsequent infection of the liver with WT parasites.
PLoS Biology · 345 Zitationen · DOI
Plasmodium sporozoite invasion of liver cells has been an extremely elusive event to study. In the prevailing model, sporozoites enter the liver by passing through Kupffer cells, but this model was based solely on incidental observations in fixed specimens and on biochemical and physiological data. To obtain direct information on the dynamics of sporozoite infection of the liver, we infected live mice with red or green fluorescent Plasmodium berghei sporozoites and monitored their behavior using intravital microscopy. Digital recordings show that sporozoites entering a liver lobule abruptly adhere to the sinusoidal cell layer, suggesting a high-affinity interaction. They glide along the sinusoid, with or against the bloodstream, to a Kupffer cell, and, by slowly pushing through a constriction, traverse across the space of Disse. Once inside the liver parenchyma, sporozoites move rapidly for many minutes, traversing several hepatocytes, until ultimately settling within a final one. Migration damage to hepatocytes was confirmed in liver sections, revealing clusters of necrotic hepatocytes adjacent to structurally intact, sporozoite-infected hepatocytes, and by elevated serum alanine aminotransferase activity. In summary, malaria sporozoites bind tightly to the sinusoidal cell layer, cross Kupffer cells, and leave behind a trail of dead hepatocytes when migrating to their final destination in the liver.
Frontiers in Cellular and Infection Microbiology · 253 Zitationen · DOI
Cerebral malaria is among the major causes of malaria-associated mortality and effective adjunctive therapeutic strategies are currently lacking. Central pathophysiological processes involved in the development of cerebral malaria include an imbalance of pro- and anti-inflammatory responses to <i>Plasmodium</i> infection, endothelial cell activation, and loss of blood-brain barrier integrity. However, the sequence of events, which initiates these pathophysiological processes as well as the contribution of their complex interplay to the development of cerebral malaria remain incompletely understood. Several cytokines and chemokines have repeatedly been associated with cerebral malaria severity. Increased levels of these inflammatory mediators could account for the sequestration of leukocytes in the cerebral microvasculature present during cerebral malaria, thereby contributing to an amplification of local inflammation and promoting cerebral malaria pathogenesis. Herein, we highlight the current knowledge on the contribution of cytokines and chemokines to the pathogenesis of cerebral malaria with particular emphasis on their roles in endothelial activation and leukocyte recruitment, as well as their implication in the progression to blood-brain barrier permeability and neuroinflammation, in both human cerebral malaria and in the murine experimental cerebral malaria model. A better molecular understanding of these processes could provide the basis for evidence-based development of adjunct therapies and the definition of diagnostic markers of disease progression.
Proceedings of the National Academy of Sciences · 212 Zitationen · DOI
The ubiquitin-like protein SMT3 from Saccharomyces cerevisiae and SUMO-1, its mammalian homolog, can be covalently attached to other proteins posttranslationally. Conjugation of ubiquitin requires the activities of ubiquitin-activating (E1) and -conjugating (E2) enzymes and proceeds via thioester-linked enzyme-ubiquitin intermediates. Herein we show that UBC9, one of the 13 different E2 enzymes from yeast, is required for SMT3 conjugation in vivo. Moreover, recombinant yeast and mammalian UBC9 enzymes were found to form thioester complexes with SMT3 and SUMO-1, respectively. This suggests that UBC9 functions as an E2 in a SMT3/SUMO-1 conjugation pathway analogous to ubiquitin-conjugating enzymes. The role of yeast UBC9 in cell cycle progression may thus be mediated through its SMT3 conjugation activity.
Journal of Biological Chemistry · 207 Zitationen · DOI
Injection of Plasmodium salivary gland sporozoites into the vertebrate host by Anopheles mosquitoes initiates malaria infection. Sporozoites develop within oocysts in the mosquito midgut and then enter and mature in the salivary glands. Although morphologically similar, oocyst sporozoites and salivary gland sporozoites differ strikingly in their infectivity to the mammalian host, ability to elicit protective immune responses, and cell motility. Here, we show that differential gene expression coincides with these dramatic phenotypic differences. Using suppression subtractive cDNA hybridization we identified highly up-regulated mRNAs transcribed from 30 distinct genes in salivary gland sporozoites. Of those genes, 29 are not significantly expressed in the parasite's blood stages. The most frequently recovered transcript encodes a protein kinase. Developmental up-regulation of specific mRNAs in the infectious transmission stage of Plasmodium indicates that their translation products may have unique roles in hepatocyte infection and/or development of liver stages.
Cell Host & Microbe · 192 Zitationen · DOI
Journal of Cell Science · 192 Zitationen · DOI
Apicomplexan host cell invasion and gliding motility depend on the parasite's actomyosin system located beneath the plasma membrane of invasive stages. Myosin A (MyoA), a class XIV unconventional myosin, is the motor protein. A model has been proposed to explain how the actomyosin motor operates but little is known about the components, topology and connectivity of the motor complex. Using the MyoA neck and tail domain as bait in a yeast two-hybrid screen we identified MTIP, a novel 24 kDa protein that interacts with MyoA. Deletion analysis shows that the 15 amino-acid C-terminal tail domain of MyoA, rather than the neck domain, specifically interacts with MTIP. In Plasmodium sporozoites MTIP localizes to the inner membrane complex (IMC), where it is found clustered with MyoA. The data support a model for apicomplexan motility and invasion in which the MyoA motor protein is associated via its tail domain with MTIP, immobilizing it at the outer IMC membrane. The head domain of the immobilized MyoA moves actin filaments that, directly or via a bridging protein, connect to the cytoplasmic domain of a transmembrane protein of the TRAP family. The actin/TRAP complex is then redistributed by the stationary MyoA from the anterior to the posterior end of the zoite, leading to its forward movement on a substrate or to penetration of a host cell.
The Journal of Experimental Medicine · 171 Zitationen · DOI
The Plasmodium life cycle is a sequence of alternating invasive and replicative stages within the vertebrate and invertebrate hosts. How malarial parasites exit their host cells after completion of reproduction remains largely unsolved. Inhibitor studies indicated a role of Plasmodium cysteine proteases in merozoite release from host erythrocytes. To validate a vital function of malarial cysteine proteases in active parasite egress, we searched for target genes that can be analyzed functionally by reverse genetics. Herein, we describe a complete arrest of Plasmodium sporozoite egress from Anopheles midgut oocysts by targeted disruption of a stage-specific cysteine protease. Our findings show that sporozoites exit oocysts by parasite-dependent proteolysis rather than by passive oocyst rupture resulting from parasite growth. We provide genetic proof that malarial cysteine proteases are necessary for egress of invasive stages from their intracellular compartment and propose that similar cysteine protease-dependent mechanisms occur during egress from liver-stage and blood-stage schizonts.
The EMBO Journal · 166 Zitationen · DOI
Science Translational Medicine · 145 Zitationen · DOI
Malaria remains the most prevalent vector-borne infectious disease and has the highest rates of fatality. Current antimalarial drug strategies cure malaria or prevent infections but lack a sustained public health impact because they fail to expedite the acquisition of protective immunity. We show that antibiotic administration during transmission of the parasite Plasmodium berghei results in swift acquisition of long-lived, life cycle-specific protection against reinfection with live sporozoites in mice. Antibiotic treatment specifically inhibits the biogenesis and inheritance of the apicoplast in Plasmodium liver stages, resulting in continued liver-stage maturation but subsequent failure to establish blood-stage infection. Exponential expansion of these attenuated liver-stage merozoites from a single sporozoite induces potent immune protection against malaria. If confirmed in residents of malaria-endemic areas, periodic prophylaxis with safe and affordable antibiotics may offer a powerful shortcut toward a needle-free surrogate malaria immunization strategy.
Molecular Microbiology · 143 Zitationen · DOI
Invasive sporozoite and merozoite stages of malaria parasites that infect mammals enter and subsequently reside in hepatocytes and red blood cells respectively. Each invasive stage may exhibit unique adaptations that allow it to interact with and survive in its distinct host cell environment, and these adaptations are likely to be controlled by differential gene expression. We used suppression subtractive hybridization (SSH) of Plasmodium yoelii salivary gland sporozoites versus merozoites to identify stage-specific pre-erythrocytic transcripts. Sequencing of the SSH library and matching the cDNA sequences to the P. yoelii genome yielded 25 redundantly tagged genes including the only two previously characterized sporozoite-specific genes encoding the circumsporozoite protein (CSP) and thrombospondin-related anonymous protein (TRAP). Twelve novel genes encode predicted proteins with signal peptides, indicating that they enter the secretory pathway of the sporozoite. We show that one novel protein bearing a thrombospondin type 1 repeat (TSR) exhibits an expression pattern that suggests localization in the sporozoite secretory rhoptry organelles. In addition, we identified a group of four genes encoding putative low-molecular-mass proteins. Two proteins in this group exhibit an expression pattern similar to TRAP, and thus possibly localize in the sporozoite secretory micronemes. Proteins encoded by the differentially expressed genes identified here probably mediate specific interactions of the sporozoite with the mosquito vector salivary glands or the mammalian host hepatocyte and are not used during merozoite-red blood cell interactions.
Immunological Reviews · 141 Zitationen · DOI
Malaria is a vector-borne infectious disease caused by unicellular parasites of the genus Plasmodium. These obligate intracellular parasites have the unique capacity to infect and replicate within erythrocytes, which are terminally differentiated host cells that lack antigen presentation pathways. Prior to the cyclic erythrocytic infections that cause the characteristic clinical symptoms of malaria, the parasite undergoes an essential and clinically silent expansion phase in the liver. By infecting privileged host cells, employing programs of complex life stage conversions and expressing varying immunodominant antigens, Plasmodium parasites have evolved mechanisms to downmodulate protective immune responses against ongoing and even future infections. Consequently, anti-malaria immunity develops only gradually over many years of repeated and multiple infections in endemic areas. The identification of immune correlates of protection among the abundant non-protective host responses remains a research priority. Understanding the molecular and immunological mechanisms of the crosstalk between the parasite and the host is a prerequisite for the rational discovery and development of a safe, affordable, and protective anti-malaria vaccine.
Proceedings of the National Academy of Sciences · 131 Zitationen · DOI
As the only volant mammals, bats are captivating for their high taxonomic diversity, for their vital roles in ecosystems--particularly as pollinators and insectivores--and, more recently, for their important roles in the maintenance and transmission of zoonotic viral diseases. Genome sequences have identified evidence for a striking expansion of and positive selection in gene families associated with immunity. Bats have also been known to be hosts of malaria parasites for over a century, and as hosts, they possess perhaps the most phylogenetically diverse set of hemosporidian genera and species. To provide a molecular framework for the study of these parasites, we surveyed bats in three remote areas of the Upper Guinean forest ecosystem. We detected four distinct genera of hemosporidian parasites: Plasmodium, Polychromophilus, Nycteria, and Hepatocystis. Intriguingly, the two species of Plasmodium in bats fall within the clade of rodent malaria parasites, indicative of multiple host switches across mammalian orders. We show that Nycteria species form a very distinct phylogenetic group and that Hepatocystis parasites display an unusually high diversity and prevalence in epauletted fruit bats. The diversity and high prevalence of novel lineages of chiropteran hemosporidians underscore the exceptional position of bats among all other mammalian hosts of hemosporidian parasites and support hypotheses of pathogen tolerance consistent with the exceptional immunology of bats.
Proceedings of the National Academy of Sciences · 131 Zitationen · DOI
Most studies of gene expression in Plasmodium have been concerned with asexual and/or sexual erythrocytic stages. Identification and cloning of genes expressed in the preerythrocytic stages lag far behind. We have constructed a high quality cDNA library of the Plasmodium sporozoite stage by using the rodent malaria parasite P. yoelii, an important model for malaria vaccine development. The technical obstacles associated with limited amounts of RNA material were overcome by PCR-amplifying the transcriptome before cloning. Contamination with mosquito RNA was negligible. Generation of 1,972 expressed sequence tags (EST) resulted in a total of 1,547 unique sequences, allowing insight into sporozoite gene expression. The circumsporozoite protein (CS) and the sporozoite surface protein 2 (SSP2) are well represented in the data set. A BLASTX search with all tags of the nonredundant protein database gave only 161 unique significant matches (P(N) < or = 10(-4)), whereas 1,386 of the unique sequences represented novel sporozoite-expressed genes. We identified ESTs for three proteins that may be involved in host cell invasion and documented their expression in sporozoites. These data should facilitate our understanding of the preerythrocytic Plasmodium life cycle stages and the development of preerythrocytic vaccines.
PLoS Pathogens · 126 Zitationen · DOI
Plasmodium sporozoites invade host hepatocytes and develop as liver stages (LS) before the onset of erythrocytic infection and malaria symptoms. LS are clinically silent, and constitute ideal targets for causal prophylactic drugs and vaccines. The molecular and cellular mechanisms underlying LS development remain poorly characterized. Here we describe a conserved Plasmodium asparagine-rich protein that is specifically expressed in sporozoites and liver stages. Gene disruption in Plasmodium berghei results in complete loss of sporozoite infectivity to rodents, due to early developmental arrest after invasion of hepatocytes. Mutant sporozoites productively invade host cells by forming a parasitophorous vacuole (PV), but subsequent remodelling of the membrane of the PV (PVM) is impaired as a consequence of dramatic down-regulation of genes encoding PVM-resident proteins. These early arrested mutants confer only limited protective immunity in immunized animals. Our results demonstrate the role of an asparagine-rich protein as a key regulator of Plasmodium sporozoite gene expression and LS development, and suggest a requirement of partial LS maturation to induce optimal protective immune responses against malaria pre-erythrocytic stages. These findings have important implications for the development of genetically attenuated parasites as a vaccine approach.
The Journal of Infectious Diseases · 126 Zitationen · DOI
At present, radiation-attenuated plasmodia sporozoites ( gamma -spz) is the only vaccine that induces sterile and lasting protection in malaria-naive humans and laboratory rodents. However, gamma -spz are not without risks. For example, the heterogeneity of the gamma -spz could explain occasional breakthrough infections. To avoid this possibility, we constructed a double-knockout P. berghei parasite by removing 2 genes, UIS3 and UIS4, that are up-regulated in infective spz. We evaluated the double-knockout Pbuis3(-)/4(-) parasites for protective efficacy and the contribution of CD8(+) T cells to protection. Pbuis3(-)/4(-) spz induced sterile and protracted protection in C57BL/6 mice. Protection was linked to CD8(+) T cells, given that mice deficient in beta (2)m were not protected. Pbuis3(-)/4(-) spz-immune CD8(+) T cells consisted of effector/memory phenotypes and produced interferon- gamma . On the basis of these observations, we propose that the development of genetically attenuated P. falciparum parasites is warranted for tests in clinical trials as a pre-erythrocytic stage vaccine candidate.
Trends in Parasitology · 121 Zitationen · DOI
Cold Spring Harbor Perspectives in Medicine · 117 Zitationen · DOI
<i>Plasmodium</i> sporozoite transmission is a critical population bottleneck in parasite life-cycle progression and, hence, a target for prophylactic drugs and vaccines. The recent progress of a candidate antisporozoite subunit vaccine formulation to licensure highlights the importance of sporozoite transmission intervention in the malaria control portfolio. Sporozoites colonize mosquito salivary glands, migrate through the skin, penetrate blood vessels, breach the liver sinusoid, and invade hepatocytes. Understanding the molecular and cellular mechanisms that mediate the remarkable sporozoite journey in the invertebrate vector and the vertebrate host can inform evidence-based next-generation drug development programs and immune intervention strategies.
Nature Communications · 98 Zitationen · DOI
Assigning function to orphan membrane transport proteins and prioritizing candidates for detailed biochemical characterization remain fundamental challenges and are particularly important for medically relevant pathogens, such as malaria parasites. Here we present a comprehensive genetic analysis of 35 orphan transport proteins of Plasmodium berghei during its life cycle in mice and Anopheles mosquitoes. Six genes, including four candidate aminophospholipid transporters, are refractory to gene deletion, indicative of essential functions. We generate and phenotypically characterize 29 mutant strains with deletions of individual transporter genes. Whereas seven genes appear to be dispensable under the experimental conditions tested, deletion of any of the 22 other genes leads to specific defects in life cycle progression in vivo and/or host transition. Our study provides growing support for a potential link between heavy metal homeostasis and host switching and reveals potential targets for rational design of new intervention strategies against malaria.
American Journal Of Pathology · 97 Zitationen · DOI
International Journal of Medical Microbiology · 96 Zitationen · DOI
Cellular Microbiology · 94 Zitationen · DOI
Male gametogenesis occurs directly after uptake of malaria parasites by the mosquito vector and leads to the release of eight nucleated flagellar gametes. Here, we report that one of the two parasite actin isoforms, named actin II, is essential for this process. Disruption of actin II in Plasmodium berghei resulted in viable asexual blood stages, but male gametogenesis was specifically inhibited. Upon activation, male gametocyte DNA was replicated normally and axonemes assembled, but egress from the host cell was inhibited, and axoneme motility abolished. The major actin isoform, actin I, displayed dual localization to the cytoplasm and the nucleus in male gametocytes. After activation actin I was found to be restricted to the cytoplasm. In actII(-) mutant parasites, this re-localization was abolished and actin I remained in both cellular compartments. These findings reveal vital and pleiotropic functions for the actin II isoform in male gametogenesis of the malaria parasite.
Kooperationen7
Bestätigte Forscher↔Partner-Paare aus HU-FIS — Gold-Standard-Positive für das Matching.
IGRK 2290: Grenzen überwinden: Molekulare Interaktionen bei Malaria
university
GRK 2046/2: Parasiteninfektionen: Von experimentellen Modellen zu natürlichen Systemen (TP B01)
university
GRK 2046/2: Parasiteninfektionen: Von experimentellen Modellen zu natürlichen Systemen
university
GRK 2046/2: Parasiteninfektionen: Von experimentellen Modellen zu natürlichen Systemen (TP B01)
other
GRK 2046/2: Parasiteninfektionen: Von experimentellen Modellen zu natürlichen Systemen (TP B01)
other
GRK 2046/2: Parasiteninfektionen: Von experimentellen Modellen zu natürlichen Systemen (TP B01)
other
GRK 2046/2: Parasiteninfektionen: Von experimentellen Modellen zu natürlichen Systemen
research_institute
Stammdaten
Identität, Organisation und Kontakt aus HU-FIS.
- Name
- Prof. Dr. Kai Matuschewski
- Titel
- Prof. Dr.
- Fakultät
- Lebenswissenschaftliche Fakultät
- Institut
- Institut für Biologie
- Arbeitsgruppe
- Molekulare Parasitologie II
- Telefon
- +49 30 2093-98552
- HU-FIS-Profil
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- Zuletzt gescrapt
- 26.4.2026, 01:09:09