ITQB: IBN - MA Dissertations
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- Biochemical characterization of the cytochrome c1 heme lyase from Plasmodium falciparumPublication . Frazão, Martim Maria de Noronha Wolfango Franco; Louro, Ricardo Saraiva Loureiro Oliveira; Alves, Alexandra S.Malaria remains one of the most significant infectious diseases worldwide, causing hundreds of millions of clinical cases and hundreds of thousands of deaths each year, with the greatest burden borne by young children under five years old and pregnant women in sub-Saharan Africa. Despite ongoing control efforts, the emergence and spread of resistance to current antimalarial therapies threaten recent gains in disease reduction, underscoring the urgent need for novel drug targets and therapeutic strategies. The most lethal form of human malaria is caused by the apicomplexan parasite Plasmodium falciparum. Although the parasite exhibits a streamlined mitochondrial metabolism compared to its human host, mitochondrial function remains essential for parasite survival, particularly for electron transport and redox balance. Central to mitochondrial respiration are cytochrome c and c1, whose activity depends on heme availability and its covalent attachment to the apocytochrome. This maturation step is catalyzed by two proteins, cytochrome c heme lyase (CCHL) and cytochrome c1 heme lyase (CC1HL) respectively, which are essential enzymes in eukaryotes and functionally different between parasites and their mammalian hosts. As such, P. falciparum’s CC1HL represents a potential vulnerability in parasite metabolism and an attractive candidate for antimalarial drug development.
- Biofuel production by sunlight using the biohybrid system Shewanella oneidensis-CdSPublication . Hapke, Henrik; Paquete, Catarina; Neves, Mónica"Rising energy demand due to a growing population while reducing global warming is one of the biggest challenges for humankind today. Hydrogen, with excellent energy properties and no burning emissions, poses the ability to solve both. However, the production of hydrogen still relies on fossil fuels which in turn makes it not sustainable. One innovative and sustainable approach under study is the use of biohybrids constructed with non-photosynthetic bacteria and the self-produced semiconductor for the production of hydrogen from sunlight. In this study a biohybrid using the electroactive bacterium Shewanella oneidensis MR-1 coupled to self-precipitated cadmium sulphide nanoparticles was constructed for hydrogen production using visible light. The electron transfer pathway involved in this bioprocess was investigated for the first time by using knock-out strains of the proteins involved in the extracellular electron transfer. These mutant strains were used to construct the biohybrids and comparing their hydrogen production to the one constructed with wild type strain, the key proteins involved in the electron uptake for hydrogen production via nanoparticles were identified.(...)"
- Optimization of cell-surface exposed cytochrome in Shewanella oneidensis MR-1 (SOMR-1) for practical implementation of bioelectrochemical systemsPublication . Clerici, Giovanni Rusconi; Paquete, Catarina; Louro, Ricardo"Bioelectrochemical systems (BESs) are unique devices capable to convert chemical energy into electrical energy (and vice-versa) through the metabolism of specific microorganisms, under anaerobic conditions. Extracellular electron transfer (EET) is the key metabolic trait that allows electroactive bacteria to connect their intracellular metabolism with external electron acceptors, including electrodes in BES. Shewanella oneidensis MR-1 (SOMR-1) is considered a model organism to study EET mechanism. In the absence of oxygen, the electrons generated in the cytoplasm by catabolic processes must flow outside of the cell envelope. (...)"
- Exploring cytochrome-c’s biogenesis in eukaryotesPublication . Raposo, Inês Tomàs de Aquino; Louro, Ricardo Oliveira"C-type cytochromes are proteins ubiquitous to organisms from all domains of Life. They play essential roles in diverse processes, ranging from electron shuttles to participating in enzymatic active sites in organism’s metabolism and triggering apoptosis within cells. Contrary to other types of cytochromes, the haem cofactor is bound to the polypeptide chain of the holoprotein. For this process to occur, a maturation system capable of catalysing this reaction is required. Although these systems are well studied and characterised in other organisms, there is a clear lack of knowledge regarding System III, which is present in eukaryotes. System III is composed of a single protein, CCHL (in yeast) or HCCS (in humans). This makes it the simplest one, with CCHL being involved in both the import of the polypeptide and the covalent attachment of the haem to the polypeptide after recognition of a specific binding motif, CXXCH.(...)"
- Emerging human pathogens from the Shewanella genus: understanding the molecular mechanism behind ferric iron-siderophore reductionPublication . Trindade, Inês de Brito; Louro, Ricardo; Fonseca, Bruno"Shewanella are Gram-negative rod-shaped bacteria that colonize diverse environments. Nevertheless, over the past years, reports have increasingly identified particular Shewanella spp. as opportunistic human pathogens. Reaching up to almost 300 cases of accounted infections, higher frequency was found in warm climates and usually includes the exposure to sea water. To date there is virtually no research on Shewanella’s pathogenicity, however iron acquisition during infection of a host plays an important role and it is a challenge that every pathogen encounters. Siderophore-mediated iron acquisition provides pathogens with the ability of circumventing the host’s immune defense and for this reason the siderophore pathway has been extensively explored. One of the least explored processes is siderophore recycling, the reduction of the ferric siderophores mediated by siderophore-interacting proteins. These fall into two subfamilies, the SIP flavoproteins and the FSR proteins containing an iron-sulfur cluster.(...)"
