Spatiotemporal mechanisms for actomyosin ring assembly and contraction in budding yeast cell division

Dissertation presented to obtain the Ph.D degree in Molecular Medicine

Analysis of panoramio photo tags in order to extract land use information

In the recent past, hardly anyone could predict this course of GIS development. GIS is moving from desktop to cloud. Web 2.0 enabled people to input data into web. These data are becoming increasingly geolocated. Big amounts of data formed something that is called "Big Data". Scientists still don't know how to deal with it completely. Different Data Mining tools are used for trying to extract some useful information from this Big Data. In our study, we also deal with one part of these data - User Generated Geographic Content (UGGC). The Panoramio initiative allows people to upload photos and describe them with tags. These photos are geolocated, which means that they have exact location on the Earth's surface according to a certain spatial reference system. By using Data Mining tools, we are trying to answer if it is possible to extract land use information from Panoramio photo tags. Also, we tried to answer to what extent this information could be accurate. At the end, we compared different Data Mining methods in order to distinguish which one has the most suited performances for this kind of data, which is text. Our answers are quite encouraging. With more than 70% of accuracy, we proved that extracting land use information is possible to some extent. Also, we found Memory Based Reasoning (MBR) method the most suitable method for this kind of data in all cases.

Contribution to drug discovery and development for tauopathies using yeast as a model

This work aimed to contribute to drug discovery and development (DDD) for tauopathies, while expanding our knowledge on this group of neurodegenerative disorders, including Alzheimer’s disease (AD). Using yeast, a recognized model for neurodegeneration studies, useful models were produced for the study of tau interaction with beta-amyloid (Aβ), both AD hallmark proteins. The characterization of these models suggests that these proteins co-localize and that Aβ1-42, which is toxic to yeast, is involved in tau40 phosphorylation (Ser396/404) via the GSK-3β yeast orthologue, whereas tau seems to facilitate Aβ1-42 oligomerization. The mapping of tau’s interactome in yeast, achieved with a tau toxicity enhancer screen using the yeast deletion collection, provided a novel framework, composed of 31 genes, to identify new mechanisms associated with tau pathology, as well as to identify new drug targets or biomarkers. This genomic screen also allowed to select the yeast strain mir1Δ-tau40 for development of a new GPSD2TM drug discovery screening system. A library of unique 138 marine bacteria extracts, obtained from the Mid-Atlantic Ridge hydrothermal vents, was screened with mir1Δ-tau40. Three extracts were identified as suppressors of tau toxicity and constitute good starting points for DDD programs. mir1Δ strain was sensitive to tau toxicity, relating tau pathology with mitochondrial function. SLC25A3, the human homologue of MIR1, codes for the mitochondrial phosphate carrier protein (PiC). Resorting to iRNA, SLC25A3 expression was silenced in human neuroglioma cells, as a first step towards the engineering of a neural model for replicating the results obtained in yeast. This model is essential to understand the mechanisms of tau toxicity at the mitochondrial level and to validate PiC as a relevant drug target. The set of DDD tools here presented will foster the development of innovative and efficacious therapies, urgently needed to cope with tau-related disorders of high human and social-economic impact.