A5076988529- Malaria Research and Control
- Mosquito-borne diseases and control
- interferon and immune responses
- Trypanosoma species research and implications
- Invertebrate Immune Response Mechanisms
- Research on Leishmaniasis Studies
- Biochemical and Molecular Research
- Immune Response and Inflammation
- Influenza Virus Research Studies
- Synthesis and Biological Evaluation
- Calcium signaling and nucleotide metabolism
- Viral Infections and Vectors
- Complement system in diseases
- Leptospirosis research and findings
- S100 Proteins and Annexins
- Enzyme Structure and Function
Universidade do Porto
2021-2022
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto
2017-2022
Instituto de Biologia Molecular e Celular
2017-2021
Abstract Plasmodium sporozoites deposited in the skin following a mosquito bite must migrate and invade blood vessels to complete their development liver. Once bloodstream, arrest liver sinusoids, but molecular determinants that mediate this specific homing are not yet genetically defined. Here we investigate involvement of thrombospondin-related sporozoite protein (TRSP) process using knockout berghei parasites vivo bioluminescence imaging mice. Resorting assay, trsp were found similar...
Pteridine reductase-1 (PTR1) is a promising drug target for the treatment of trypanosomiasis. We investigated potential previously identified class thiadiazole inhibitors Leishmania major PTR1 activity against Trypanosoma brucei (Tb). solved crystal structures several TbPTR1-inhibitor complexes to guide structure-based design new derivatives. Subsequent synthesis and enzyme- cell-based assays confirm new, mid-micromolar TbPTR1 with low toxicity. In particular, compound 4m,...
Since the pioneering discoveries, by Nobel laureates Jules Hoffmann and Bruce Beutler, that Toll Toll-like receptors can sense pathogenic microorganisms initiate, in vertebrates invertebrates, innate immune responses against microbial infections, many other families of pattern recognition (PRRs) have been described. One such receptor clusters is composed by, if not all, at least several members scavenger cysteine-rich (SRCR) superfamily. Many SRCR proteins are plasma membrane cells; however,...
Neglected tropical diseases caused by kinetoplastid parasites (Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp.) place a significant health economic burden on developing nations worldwide. Current therapies are largely outdated, inadequate, face mounting drug resistance from the causative parasites. Thus, there is an urgent need for discovery development. Target-led approaches have focused identification of parasite enzymes catalyzing essential biochemical processes, which...
Abstract The identification of surface proteins the sporozoite stage malaria parasites important for infectivity could aid in improvement efficacy vaccines targeting pre-erythrocytic stages. Thus, we set out to disclose role secreted protein with an altered thrombospondin repeat (SPATR), which is highly expressed sporozoites. Previous studies showed essential function blood stages, while no was detected sporozoites despite high expression. To achieve downregulation expression maintaining...
The sole currently approved malaria vaccine targets the circumsporozoite protein—the protein that densely coats surface of sporozoites, parasite stage deposited in skin mammalian host by infected mosquitoes. However, this only confers moderate protection against clinical diseases children, impelling a continuous search for novel candidates. In work, we studied importance membrane-associated erythrocyte binding-like (MAEBL) infection Plasmodium sporozoites. Using transgenic parasites and live...
Malaria is a major public health concern, as highly effective human vaccine remains elusive. The efficacy of subunit targeting the most abundant protein sporozoite surface, circumsporozoite (CSP) has been hindered by difficulties in generating an humoral response both quantity and quality. Using rodent Plasmodium yoelii model we report here that immunization with CSP adjuvanted 5’ppp-dsRNA, RIG-I agonist, confers early long-lasting sterile protection mice against stringent mosquito bite...