A5016643521- Malaria Research and Control
- Mosquito-borne diseases and control
- Invertebrate Immune Response Mechanisms
- Complement system in diseases
- HIV Research and Treatment
- Parasites and Host Interactions
- Genomics and Chromatin Dynamics
- Drug Transport and Resistance Mechanisms
- RNA Research and Splicing
- vaccines and immunoinformatics approaches
- Trypanosoma species research and implications
- Sperm and Testicular Function
- Lipid Membrane Structure and Behavior
- RNA and protein synthesis mechanisms
- Heat shock proteins research
- Plant Reproductive Biology
- Aquaculture disease management and microbiota
- RNA Interference and Gene Delivery
- Antimicrobial Peptides and Activities
- Research on Leishmaniasis Studies
- Insect Resistance and Genetics
- Chromosomal and Genetic Variations
- Erythrocyte Function and Pathophysiology
- Nanoparticle-Based Drug Delivery
- DNA and Nucleic Acid Chemistry
Institució Catalana de Recerca i Estudis Avançats
2016-2025
Barcelona Institute for Global Health
2016-2025
Universitat de Barcelona
2015-2024
Institut Català de Ciències del Clima
2016-2024
Departament de Salut
2024
Institute for Research in Biomedicine
2007-2015
The University of Queensland
2014
Translational Research Institute
2014
Barcelona Centre for International Affairs
2012-2013
Papua New Guinea Institute of Medical Research
2002-2009
Malaria genetic variation has been extensively characterized, but the level of epigenetic plasticity remains largely unexplored. Here we provide a comprehensive characterization transcriptional in most lethal malaria parasite, Plasmodium falciparum, based on highly accurate analysis isogenic parasite lines grown under homogeneous conditions. This revealed extensive heterogeneity within genetically clonal populations. We show that clonally variant expression controlled at is an intrinsic...
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a major pathogenicity factor in malaria that mediates cytoadherence. PfEMP1 encoded by approximately 60 var genes per haploid genome. Most are grouped into 3 subgroups: A, B, and C. Evidence emerging the specific expression of these subgroups has clinical significance. Using field samples from children Papua New Guinea with severe, mild, asymptomatic malaria, we compared proportions transcripts groups, as determined...
The process of erythrocyte invasion by merozoites Plasmodium falciparum involves multiple steps, including the formation a moving junction between parasite and host cell, it is characterised redundancy many receptor–ligand interactions involved. Several proteins that interact with receptors or participate in other steps are encoded small subtelomerically located gene families four to seven members. We report here members eba, rhoph1/clag, acbp, pfRh multigene exist either an active silenced...
Malaria transmission requires that some asexual parasites convert into sexual forms termed gametocytes. The initial stages of development, including sexually committed schizonts and rings, remain poorly characterized, mainly because they are morphologically identical to their counterparts only a small subset undergo development. Here, we describe system for controlled conversion in the human malaria parasite Plasmodium falciparum, based on conditional expression PfAP2-G transcription factor....
Significance Malaria remains one of the main health threats in developing world, with staggering social and economic costs. Resistance to artemisins, pharmacological tool currently available against malaria, has been widely reported. Borrelidin, a natural compound that inhibits threonyl-tRNA synthetase, long studied for its antibacterial antiparasitic properties, but undesirable toxic effects prevented further clinical development. Here we present group borrelidin derivatives retain their...
ABSTRACT Plasmodium falciparum apical membrane antigen 1 (AMA1) is a prime malaria vaccine candidate. Antigenic diversity within parasite populations one of the main factors potentially limiting efficacy any asexual-stage vaccine, including based on AMA1. The DNA coding for most variable region this antigen, domain I, was sequenced in 168 samples from Wosera Papua New Guinea, symptomatic and asymptomatic infections. Neutrality tests applied to these sequences provided strong evidence...
Clonally variant gene expression is a common survival strategy used by many pathogens, including the malaria parasite Plasmodium falciparum. Among genes that show in this are several members of small families linked to erythrocyte invasion, clag and eba families. The active or repressed state these clonally transmitted epigenetic mechanisms. Here we characterized promoters clag3.1, clag3.2 eba-140, compared nuclease accessibility post-translational histone modifications between their states....
Malaria parasites induce changes in the permeability of infected erythrocyte membrane to numerous solutes, including toxic compounds. In Plasmodium falciparum, this is mainly mediated by PSAC, a broad-selectivity channel that requires product parasite clag3 genes for its activity. The two paralogous genes, clag3.1 and clag3.2, can be silenced epigenetic mechanisms show mutually exclusive expression. Here we resistance antibiotic blasticidin S (BSD) associated with switches expression these...
Human malaria is a devastating disease and major cause of poverty in resource-limited countries. To develop adapt within hosts Plasmodium falciparum undergoes drastic switches gene expression. identify regulatory regions the parasite genome, we performed genome-wide profiling chromatin accessibility two culture-adapted isogenic subclones at four developmental stages during intraerythrocytic cycle by using Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq). Tn5 transposase...
Abstract Transmission of malaria parasites from humans to mosquito vectors requires that some asexual differentiate into sexual forms termed gametocytes. The balance between proliferation in the same host and conversion transmission can be altered by conditions environment. ability accurately measure rate under different is essential for research addressing mechanisms underlying conversion, assess impact environmental factors. Here we describe new Plasmodium falciparum transgenic lines with...
Malaria transmission is dependent on the formation of gametocytes in human blood. The sexual conversion rate, proportion asexual parasites that convert into at each multiplication cycle, variable and reflects relative parasite investment between maintaining infection. impact environmental factors such as drugs rates not well understood. We developed a robust assay using gametocyte-reporter lines to accurately measure rates, independently from their gametocytocidal activity. found exposure...
ABSTRACT Antibody responses against proteins located on the surface or in apical organelles of merozoites are presumed to be important components naturally acquired protective immune malaria parasite Plasmodium falciparum . However, many merozoite antigens highly polymorphic, and antibodies induced one particular allelic form might not effective controlling growth parasites expressing alternative forms. The membrane antigen 1 (AMA1) is a polymorphic protein that target invasion-inhibitory...
BackgroundThe variable antigen P. falciparum erythrocyte membrane protein-1 (PfEMP1) is a major virulence factor in malaria. A large number of var genes encode PfEMP1, and we hypothesized that restricted PfEMP1 repertoire determines clinical disease presentation. We conducted case-control study Papua New Guinea analyzed transcribed naturally infected children.
Paul Ehrlich's dream of a 'magic bullet' that would specifically destroy invading microbes is now major aspect clinical medicine. However, century later, the implementation this medical holy grail continues being challenge in three main fronts: identifying right molecular or cellular targets for particular disease, having drug effective against it, and finding strategy efficient delivery sufficient amounts an active state exclusively to selected targets. In previous work, we engineered...
The ability of malaria parasites to adapt changes in the human blood environment, where they produce long-term infection associated with clinical symptoms, is fundamental for their survival. CVGs, regulated at epigenetic level, play a major role this adaptive process, as expression these genes result alterations antigenic and functional properties parasites.
The interaction between the Plasmodium vivax merozoite Duffy binding protein region II (DBPII) and human erythrocyte antigen leads to infection. Highly polymorphic regions of this may have arisen as a mechanism avoid host immunity. To examine whether immunity P. is directed against these DBPII, age-associated changes in frequency specific DBPII alleles among 358 vivax–positive Papua New Guineans were examined. Although overall number diversity haplotypes simultaneously infecting an...
The product of the Plasmodium falciparum genes clag3.1 and clag3.2 plays a fundamental role in malaria parasite biology by determining solute transport into infected erythrocytes. Expression two clag3 is mutually exclusive, such that single expresses only one at time. Here we investigated properties mechanisms mutual exclusion using transgenic lines with extra copies promoters located either stable episomes or integrated genome. We found additional these are silenced default, but under...