A5060606769- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Insect symbiosis and bacterial influences
- Immune Cell Function and Interaction
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Lipid Membrane Structure and Behavior
- Biochemical and Molecular Research
- HVDC Systems and Fault Protection
- Galectins and Cancer Biology
- Cardiac Structural Anomalies and Repair
- Calcium signaling and nucleotide metabolism
- Lipid metabolism and biosynthesis
- Monoclonal and Polyclonal Antibodies Research
- Cellular transport and secretion
- Complement system in diseases
- Parasites and Host Interactions
- Bacterial Genetics and Biotechnology
- Photosynthetic Processes and Mechanisms
- Superconducting Materials and Applications
German Cancer Research Center
2018-2023
Heidelberg University
2018-2023
University of Lisbon
2012-2022
DKFZ-ZMBH Alliance
2021
Hospital de Egas Moniz
2014
Rede de Química e Tecnologia
2010
Trypanosoma brucei is an extracellular parasite that causes sleeping sickness. In mammalian hosts, trypanosomes are thought to exist in two major niches: early infection, they populate the blood; later, breach blood-brain barrier. Working with a well-established mouse model, we discovered adipose tissue constitutes third reservoir for T. brucei. Parasites from tissue, here termed forms (ATFs), can replicate and were capable of infecting naive animal. ATFs transcriptionally distinct...
The plasma membrane of Saccharomyces cerevisiae was studied using the probes trans-parinaric acid and diphenylhexatriene. Diphenylhexatriene anisotropy is a good reporter global order. fluorescence lifetimes are particularly sensitive to presence nature ordered domains, but thus far they have not been measured in yeast cells. A long lifetime typical gel phase (>30 ns) found wild-type (WT) cells from two different genetic backgrounds, at 24 30 °C, providing first direct evidence for domains...
Antigenic variation in Trypanosoma brucei relies on periodic switching of variant surface glycoproteins (VSGs), which are transcribed monoallelically by RNA polymerase I from one about 15 bloodstream expression sites (BES). Chromatin the actively BES is depleted nucleosomes, but it unclear if this open conformation a mere consequence high rate transcription, or whether maintained transcription-independent mechanism. Using an inducible BES-silencing reporter strain, we observed that chromatin...
Trypanosoma brucei is a unicellular parasite that causes sleeping sickness in humans. Most of its transcription constitutive and driven by RNA polymerase II. I (Pol I) transcribes not only ribosomal genes, but also protein-encoding including variant surface glycoproteins (VSGs) procyclins. In T. brucei, histone H1 (H1) required for VSG silencing chromatin condensation. However, whether has genome-wide role unknown. Here, using sequencing we show depletion changes the expression specific...
The African trypanosome survives the immune response of its mammalian host by antigenic variation major surface antigen (the variant glycoprotein or VSG). Here we describe antibody repertoires elicited different VSGs. We show that are highly restricted and directed predominantly to distinct epitopes on They also discriminatory; minor alterations within these exposed confer antigenically properties VSGs elicit repertoires. propose patterned repetitive nature VSG coat focuses immunity a set...
Long-term immune evasion by the African trypanosome is achieved through repetitive cycles of surface protein replacement with antigenically distinct versions dense Variant Surface Glycoprotein (VSG) coat. Thousands VSG genes and pseudo-genes exist in parasite genome that, together genetic recombination mechanisms, allow for essentially unlimited escape from adaptive system host. The diversity space "VSGnome" at level was thought to be limited a few related folds whose structures were...
Trypanosoma brucei parasites successfully evade the host immune system by periodically switching dense coat of variant surface glycoprotein (VSG) at cell surface. Each parasite expresses VSGs in a monoallelic fashion that is tightly regulated. The consequences exposing multiple during an infection, terms antibody response and disease severity, remain unknown. In this study, we overexpressed high-mobility group box protein, TDP1, which was sufficient to open chromatin silent VSG expression...
During infection of mammalian hosts, African trypanosomes thwart immunity using antigenic variation the dense Variant Surface Glycoprotein (VSG) coat, accessing a large repertoire several thousand genes and pseudogenes, switching to antigenically distinct copies. The parasite is transferred hosts by tsetse fly. In salivary glands fly, pathogen adopts metacyclic form expresses limited VSG specific that developmental stage. It has remained unknown whether VSGs possess properties associated...
Most researchers who study unicellular eukaryotes work with an extremely limited number of laboratory-adapted isolates that were obtained from the field decades ago, but effects passage in laboratory rodents, and adaptation to vitro culture, have been little studied. For example, vast majority studies Trypanosoma brucei biology concentrated on just two strains, Lister 427 EATRO1125, which taken over half a century ago since undergone innumerable passages rodents culture. We here describe new...
Summary RNA modifications are important regulators of gene expression. In Trypanosoma brucei , transcription is polycistronic and thus most regulation happens post-transcriptionally. N 6 -methyladenosine (m A) has been detected in this parasite, but its function remains unknown. Here we show that ∼50% the m A located poly(A) tail monoallelically expressed Variant Surface Glycoprotein ( VSG ) transcript. residues removed from prior to deadenylation mRNA degradation. Using genetic tools,...
African trypanosomes cause disease in humans and livestock, avoiding host immunity by changing the expression of variant surface glycoproteins (VSGs); major glycosylphosphatidylinositol (GPI) anchored antigens coating bloodstream stage. Proper trafficking VSGs is therefore critical to pathogen survival. The valence model argues that GPI anchors regulate progression fate secretory pathway that, specifically, a two (VSGs are dimers) for stable cell association. However, recent reports MITat1.3...
Abstract The African trypanosome survives the immune response of its mammalian host by antigenic variation major surface antigen (the Variable Surface Glycoprotein, or VSG). Here we describe antibody repertoires elicited different VSGs. We show that are highly restricted, and directed predominantly to distinct epitopes on They also discriminatory: minor alterations within these exposed confer antigenically-distinct properties VSGs elicit repertoires. propose patterned repetitive nature VSG...
ABSTRACT Long-term immune evasion by the African trypanosome is achieved through repetitive cycles of surface protein replacement with antigenically distinct versions dense Variant Surface Glycoprotein (VSG) coat. Thousands VSG genes and pseudo-genes exist in parasite genome that, together genetic recombination mechanisms, allow for essentially unlimited escape from host’s adaptive system. The diversity space “VSGnome” at level was thought to be limited a few related folds whose structures...
Abstract Most researchers who study unicellular eukaryotes work with an extremely limited number of laboratory-adapted isolates that were obtained from the field decades ago, but effects passage in laboratory rodents, and adaptation to vitro culture, have been little studied. For example, vast majority studies Trypanosoma brucei biology concentrated on just two strains, Lister 427 EATRO1125, which taken over half a century ago since undergone innumerable passages rodents culture. We here...
Abstract During infection of mammalian hosts, African trypanosomes thwart immunity using antigenic variation the dense Variant Surface Glycoprotein (VSG) coat, accessing a large repertoire thousands genes and pseudogenes switching to antigenically distinct copies. The parasite is transferred hosts through bite tsetse fly. In salivary glands fly, pathogen adopts metacyclic form expresses limited VSG specific that developmental stage. It has remained unknown whether VSGs possess properties...