ITQB: LA - PhD Theses
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- Psychedelics, population dynamics, and the generation of experiencePublication . Arlandis, Jaime; Mainen, Zachary; McNamee, Daniel"At its core, the present work is structured around two different innovative contributions to the field of psychedelic research: first, results from an experimental project studying the effects of a psychedelic drug in rodents, and second, a set of philosophical and theoretical contributions to the field, centered on the extrapharmacological effects of these substances. While these may seem like unrelated contributions, I will argue that they are intimately connected: they can both be seen as additions to a growing body of publications urging for a critical reappraisal of the status of the field.(...)"
- The Role of Biliverdin Reductase A in MalariaPublication . Figueiredo, Ana; Soares, Miguel; Martins, Rui"Malaria, a life-threatening disease caused by Plasmodium spp., remains a major global health burden. While considerable progress has been made in characterizing host resistance mechanisms that reduce parasite burden during Plasmodium infection, our understanding of these pathways remains incomplete. Disease tolerance mechanisms that mitigate tissue damage during infection without directly affecting parasite burden are even less well-understood. This PhD thesis explores the hypothesis that biliverdin reductase A (BVRA) and its end product, unconjugated bilirubin, confer host protection against malaria through both resistance and disease tolerance mechanisms.(...)"
- Mechanisms of cross-modal transfer in cerebellar associative learningPublication . Kruse, Merit; Carey, MeganThe ability to generalize previously learned associations to new stimuli can be an important determinant for survival. Here we investigated neural mechanisms of generalization using delay eyeblink conditioning, a cerebellum-dependent form of learning, in which mice learn to close their eyelid in response to a neutral conditioned stimulus (CS) that predicts an air puff to the eye. Consistent with previous work in other species, we found that learning in response to a CS in one sensory modality subsequently facilitates the rate of acquisition to a different modality, a process termed cross-modal transfer (CMT). We find that in mice, learning to a visual CS is more readily enhanced by previous learning to a whisker somatosensory CS than the other way around. To investigate circuit mechanisms for CMT, we used genetically modified mouse lines in combination with optogenetic delivery of the CS to different cerebellar circuit elements. We found that training to a mossy fiber optogenetic CS induces CMT to both visual and somatosensory modalities
- DeeperInsightsintoSmallMoleculesModeofTargetModulationUsingHydrogenDeuteriumExchange-MassSpectrometryPublication . Malta, Catarina Féliz; Bortoluzzi, Alessio; Bandeiras, Tiago"Hydrogen deuterium exchange mass spectrometry (HDX-MS) has emerged as a powerful tool for probing protein:ligand interactions, providing critical insights into protein dynamics, structural rearrangements, and binding mechanisms. This work explores the application of HDX-MS to study two drug target proteins, Cyclophilin D (CypD) and Autotaxin (ATX). A deeper understanding of the molecular mechanisms underlying protein:ligand interactions emerged by integrating HDX-MS with complementary biophysical techniques, such as Surface Plasmon Resonance (SPR), Isothermal Titration Calorimetry (ITC), Circular Dichroism (CD), and X-ray crystallography,(...)"
- Modeling the directionality of interactions between cortical areasPublication . Carmona, Joana Pernadas; Machens, Christian"Investigating interactions between neural populations and their relationship to coding and behavior lies at the core of neuroscience. Covariance-based approaches are commonly used to study interactions in both local and brain-wide, multi-area circuits. The effective directionality of signal flow, in particular, can be inferred from the temporal structure of cross-covariance functions. Recent studies revealed that the directionality of inter-areal interactions can shift rapidly, depending on stimuli and task demands. These findings suggest that experimentally measured covariance metrics reflect not only the underlying synaptic connectivity but also dynamic influences such as inputs from other regions. Understanding how these metrics relate to circuit-level mechanisms remains a challenging task that warrants theoretical approaches.(...)"
- Olfr56 in Sickness and in HealthPublication . Da Silva Barros, André Boler Cláudio; Moita, Luís; Veldhoen, Marc"Sepsis is a life-threatening condition that originates from an exacerbated host response to infection. Understanding the pathophysiology of sepsis is crucial for the development of new treatments. In this context, a new perspective on the immune response has emerged, focusing on sensing organismal stress as a key factor in modulating the immune system's response to infection. Uncovering the receptors sensing such signals is then a relevant question to address.(...)"
- Mechano-epigenetic control of neural crest collective cell migration in vivoPublication . Saraiva, Joana Estudante; Barriga, Elias"A number of chromatin posttranslational modifications (PTMs), such as histone methylation and acetylation, are involved in the initiation of collective cell migration (CCM) in neural crest cells and other cell types1-3. These PTMs function primarily to fine-tune the chromatin landscape to allow for appropriate patterns of gene expression that control cell fate decisions and plasticity4-7. However, how cells dynamically fine-tune transcriptional programs to adapt their behavior in response to environmental cues remains elusive. One such mark, histone H3 lysine (K) 4 trimethylation (H3K4me3), has been demonstrated to enable neural crest CCM8 and plays critical roles in reinforcing permissive gene expression. In addition, the onset of neural crest CCM is mechanically controlled by stiffening of the tissue that they use as a migratory substrate, the mesoderm (...)."
- Investigating a Noncanonical Role in Translation for Arabidopsis SR ProteinsPublication . Yáñez, Romana de Jesus Rosário; Duque, Paula"Serine/arginine-rich (SR) proteins are essential splicing regulators with well- characterised nuclear functions. Emerging evidence from animal systems indicates that they also play noncanonical roles across several layers of gene expression regulation, including mRNA transcription, nuclear export, translation and decay. In Arabidopsis thaliana, a few SR proteins have been shown to shuttle between the nucleus and cytoplasm, yet the functional significance of this dynamic behaviour in plants remains largely unexplored. This thesis investigates the nucleocytoplasmic shuttling activity of four Arabidopsis SR proteins—SR34a, SR45, RSZ21, and RS40—as a prerequisite for potential cytoplasmic post-splicing functions. (...)"
- Characterization and integration of the transcriptional programs downstream Ascl1 and Notch signaling during neurogenesis: investigating a cell-autonomous cross-talk between the two pathwaysPublication . Heskol, Abeer; Castro, Diogo; Castelo Branco, Gonçalo"Neurons are generated from multipotent neural stem cells (NSCs) by a developmental program called neurogenesis. This process is to large extent regulated by proneural transcription factors such as Ascl1, both required and sufficient to drive a full program of neuronal differentiation. However, and contrary to the initial view of Ascl1 as a classical differentiation factor, recent studies have shown Ascl1 promotes sequentially the proliferation and differentiation along the neuronal lineage.(...)"
- Mapping metabolism in a whole animal at single-cell resolutionPublication . Cardoso Figueiredo, Rita; Ribeiro, Carlos"Metabolism is a key process at the core of all cellular functions. Cell-specific metabolic activity can have an active and instructive role, impacting cellular function. Although these idiosyncrasies have started to be explored, cell-specific metabolism has not yet been mapped in a comprehensive way at the single-cell, whole-animal level.(...)"