Our laboratory is focused on studying the development and role of the thymus, the organ responsible for the generation of T cells that are simultaneously responsive against pathogens and self-tolerant.

TECs are divided into two specialized functionally distinct cortical (cTECs) and medullary (mTECs) subtypes, which derive from common bipotent TEC progenitors. We take a global approach to investigate TEC differentiation, which integrates the study of molecular processes taking place at the single-cell level to the analysis of in vivo mouse models.

Using advanced research tools that include reporter, germ-line and cell-specific knock-out mice, organotypic cultures combined with thymic transplantations and transcriptomic, our major goals are to:

• Identify TEC progenitors and their niches within the fetal and adult thymus.
• Examine the contribution of distinct TEC subsets to support T-cell development.
• Elucidate the molecular basis that control cTEC/mTEC fate decisions.
• Study the role of the thymus in pathophysiological states.

Desde o advento da medicina científica no século XIX que a investigação biomédica em animais tem contribuído significativamente para o aumento da longevidade e qualidade de vida quer dos seres humanos quer de outros animais. A experimentação animal apresenta contudo um complexo dilema ético entre os seus (potenciais) benefícios e o dano que é imposto aos animais, um problema para o qual não há uma solução universalmente aplicável e satisfatória.

Nesta apresentação irei apresentar as principais questões de ordem científica e ética relacionadas com o uso de animais em ciência, bem como o princípio dos 3Rs – para Replacement, Reduction e Refinement – como uma abordagem de compromisso e constante reavaliação e progresso no tratamento ético dos animais de laboratório.

Spinal cord injury (SCI) frequently results in permanent paraplegia and quadriplegia. Up to now no effective therapies have efficiently tackle this problem. The objective of the present work was aim to establish novel therapeutic routes that overcome the pitfalls of current methodologies. Its backbone is based on an intimate crosstalk between peptide grafted scaffolds and the secretome mesenchymal stem cells (MSCs) The objective is to develop an integrative strategy where the 3D scaffolds protect MSCs within the injured spinal cord, while the latter, through their tropich action, modulate inflammation while stimulating axonal outgrowth and neuronal differentiation. A hydrogel based biomaterial, aimed at carrying MSCs and OECs to foster SCI repair, was successfully established. In subsequent reports the hydrogel phase was further improved by grafting on its structure a GRGDS peptide, trough click chemistry. This modification proved to be pivotal for fostering the growth and differentiation of neural cells within the hydrogel, as well as to stimulate the proliferation and viability of MSCs, with an advantageous impact on their secretome. In vivo experiments in a hemissection rat SCI model revealed that the developed strategy lead to significant gains in motor function of afflicted SCI animals, when compared to non-treated controls, thus validating the strategy developed so far.

Marine toxins are chemical compounds naturally produced by microalgae or bacteria. During a toxin-producer algal bloom, toxins mainly associated with the phytoplankton cells may be ingested by shellfish (both molluscs and crustaceans), and planktivorous fish, leading to responses at organism and sub-cellular level and death under extreme episodes. Suspension-feeding mollusc bivalves are the principal vectors for the transfer of several major groups of toxins, due to their ability to pump large volumes of seawater and to concentrate toxins without massive mortality. Consumption of bivalves and other marine organisms containing high toxin concentrations may lead to human health problems.

The first works on marine toxins were focused on the assessment of bivalve toxicity through bioassays in order to protect human health. As chemical methodologies to quantify toxins improved, analytical procedures were used providing the possibility to quantify individual toxins and to characterise toxin profiles in algae and bivalves. Kinetic studies of toxins allowed to predict the time required for toxin concentrations in bivalves to meet the regulatory limits. To go further it is important to gain knowledge on the storage of assimilated toxins in tissues and their transformation mechanisms.

This presentation reviews several studies of bivalve toxicity by paralytic shellfish toxins (PSTs) in Portuguese estuarine and coastal waters including:

• Trends and connectivity of bivalve toxicity episodes over 18 years;
• Linkage between nutrient availability and maintenance of toxic algal blooms in a coastal lagoon, and consequently prolonged toxicity in bivalves;
• Biotransformation of PSTs during the bioaccumulation processes,
• Sub-cellular partitioning of PSTs in bivalve tissues.

Ageing is the major biomedical challenge of the 21st century, yet it remains largely mysterious, partly because the ageing process involves multiple genes and their interactions with each other and with the environment that remain poorly understood. In this talk, I will present genomic and computational approaches aimed at deciphering the genome and increasing our knowledge about how genes and pathways impact on ageing. Moreover, I will present a systems biology dissection of caloric restriction, a dietary manipulation of ageing, to gather insights into its regulation and identify promising drug targets. We have also been employing whole transcriptome profiling (RNA-seq) to gather insights on ageing and its manipulation by diet. Lastly, I will discuss our recent work in sequencing and analyzing the genome of the longest-lived mammal, the bowhead whale, to identify longevity assurance mechanisms.

A resistência à terapêutica antineoplásica é um problema clínico atual muito significativo, pois limita o tratamento eficaz de doentes com cancro. Os mecanismos responsáveis são diversos e complexos, como por exemplo a sobre-expressão da P-glicoproteína (que promove o efluxo celular de fármacos), mutações no alvo terapêutico do fármaco, a sobre-expressão de proteínas antiapoptóticas, ou a expressão de alguns microRNAs que controlam os níveis celulares de proteínas relevantes para a sensibilidade aos fármacos.

As vesículas extracelulares, incluindo exosomas e microvesículas, são partículas muito pequenas (normalmente entre 100 a 1000nm), rodeadas por uma camada fosfolipídica e possuindo conteúdo celular (tal como proteínas, microRNAs ou mesmo DNA) da célula que as produziu. Existem na literatura evidências recentes de que vesículas extracelulares podem ser responsáveis pela transferência intercelular de proteínas ou microRNAs associados à resistência à terapêutica antineoplásica, podendo ser responsáveis por transformar células sensíveis em células resistentes a fármacos.

Nesta apresentação serão mencionados alguns resultados obtidos pelo nosso grupo de trabalho, que evidenciam o papel das vesículas extracelulares na transferência intercelular de resistência a fármacos antineoplásicos. Serão ainda mencionados resultados que sugerem a possibilidade de utilizar estas vesículas extracelulares na pesquisa de biomarcadores de resistência à terapêutica antineoplásica.

Pretendemos clarificar o papel das mitocôndrias (energia, homeostasia e sinalização) e das vias de sinalização mediadas pela insulina nas alterações cerebrais associadas à diabetes e doença de Alzheimer. A influência do género nos mecanismos moleculares subjacentes às alterações que ocorrem no cérebro diabético com a idade é também objeto de atenção. Também estamos interessados em avaliar o potencial papel protetor de alguns antidiabéticos e moduladores da função mitocondrial nas doenças supramencionadas.

Molybdenum (Mo) and Tungsten (W) are the heaviest transition metals with a defined biological role. Both Mo and W exhibit multiple oxidation states within a biologically relevant range of reduction potentials and are capable of catalyzing different reactions that are important for the biogeochemical cycles of the most abundant elements of the Earth (N, S, C, O, within others). With the exception of the bacterial nitrogenase, which harbors a cofactor containing Fe and Mo}, Mo and W are found in the active site of enzymes in a mononuclear form, usually coordinated by one or two organic moieties (pyranopterin molecules).

This group of mononuclear Mo-containing enzymes has been classified into 3 families, according to their Mo centre structure: Xanthine oxidase (XO) (that includes Aldehyde oxidoreductases (AO)), Sulfite oxidase (SO) and Dimethylsulfoxide reductase (DMSOR) families. The W-containing enzymes are grouped in a separated family. Of these, only SO and XO families span all domains of life, and mammals have only the mammalian mitochondrial amidoxime-reducing component (mARC), SO, XO and AO enzymes.

A critical analysis of structure, function and catalytic mechanism of the Mo-containing enzymes is presented with a major focus on nitrate reductase (Nap) and formate dehydrogenase (Fdh) that belong to the DMSO reductase family. In addition, Mo (and W)-substituted Rubredoxins (a small protein that provides a rich sulfur coordination), reacted with external exogenous ligands, are discussed as suitable structural and functional models for molybdoenzymes.

A simplificação e a maior eficiência dos sistemas de rastreio do cancro podem ser conseguidas através da identificação de novas biomoléculas que permitam inferir, em fluidos biológicos, sobre o estágio da doença ou a sua evolução face ao tratamento. Essas biomoléculas são conhecidas como biomarcadores da doença, porque funcionam como indicadores biológicos da sua presença e a sua quantificação em contexto clínico constituiria um avanço significativo no combate ao cancro.

Numa tentativa de colmatar a falta de dispositivos capazes de gerar uma medida rápida e barata no local onde o doente é observado, e aproveitando a informação mais atual na literatura relativamente aos biomarcadores mais relevantes neste domínio, a BioMark, Sensor Research, desenvolve trabalho de investigação tendo em vista a implementação de um novo conceito de medida de biomarcadores, combinando a seletividade dos anticorpos plásticos como material sensor com a autonomia de operação elétrica de uma célula fotovoltaica.

O percurso seguido rumo a esta trajetória e o dispositivo em desenvolvimento serão objeto de debate na apresentação...

We are generally interested on the molecular mechanisms of ion transport across the cell membrane. Recently we have been primarily focused on mechanisms of regulation of potassium channels that involve interactions with cytosolic proteins like calmodulin, kinases and phosphatases. In these studies we combine X-ray crystallography, for three-dimensional structure determination, with different biochemical and biophysical in vitro techniques. We have also been expanding our repertoire of techniques to study the properties of these channels in cell, including electrophysiology and optical microscopy.

The delivery of molecules to organisms, either for therapy, imaging or other applications outside the biomedical field, represents a great challenge that has been addressed by the application of microencapsulation techniques. Nanoparticles and microparticles take the forefront of the field and are the most used carriers. In this lecture, the various contributions of particulate systems will be unveiled and the contribution of our research group to the field exposed.