Proyectos

The project deals with commutation principles in Euclidean Jordan Algebras, Normal Decomposition systems and Fan-Theobald-von Newman systems. It propose to deal with the generalization of these principles and the application to variational analysis and the Marcus-de Oliveira determinantal conjecture.

El cáncer es la segunda causa de muerte en la población Chilena y se proyecta que en diez años será la primera causa de muerte en el país. A nivel regional, la región de O Higgins es la que presenta la mayor incidencia de muertes por cáncer. Actualmente, Chile invierte alrededor del 1% del PIB en atención y tratamiento del cáncer. Es indispensable y urgente comenzar a caracterizar molecularmente los cánceres prevalentes de la población Chilena pues esto permitirá integrar información que impactará las decisiones clínicas permitiendo la implementación de tratamientos específicos para los pacientes. El estudio genómico y molecular de sistemas biológicos complejos, como el desarrollo y progresión del cáncer, requieren del desarrollo de nuevos algoritmos y modelos teóricos para analizar e interpretar datos genómicos complejos (big- data). El principal objetivo del laboratorio de genómica computacional que instalaré en el instituto de ciencias de la ingeniería de la Universidad de O Higgins será desarrollar investigación de vanguardia entorno al diseño y aplicación de nuevos algoritmos y tecnologías ómicas para estudiar la arquitectura genómica de cánceres prevalentes de la población Chilena. La meta a largo plazo es trasladar estas tecnologías a la práctica clínica e impulsar la implementación de programas de medicina de precisión enfocados en el tratamiento y prevención del cáncer en nuestro país y región. Un segundo objetivo es impulsar y liderar investigación multidisciplinaria en temáticas de salud, agroindustria y minería, sectores críticos a desarrollar en la región de O'Higgins. Finalmente, el laboratorio de genómica computacional contribuirá a la formación de capital humano avanzado en áreas asociadas a la genómica, bioinformática y biología computacional.

The Chilean government recently launched the national cancer plan to increase survival rates and reduce cancer incidence, which is projected to become the first cause of death in the Chilean population. Only in 2020, more than 55,000 new cases of cancer were registered. Therefore, starting the molecular characterization of the prevalent cancers of the Chilean population is urgent since this can inform therapeutic decisions and thus promote more specific treatments for patients, positively impacting survival rates and prevention. Due to the constant improvement of sequencing technologies, cancer research increasingly relies on the interpretation and analysis of high-dimensional genomic data. Genomic cancer analysis has revealed that the mutation repertoire of tumors is vast and goes from single nucleotide variants to whole-genome duplications. Structural variants (SVs) and copy number alterations are significant drivers of cancer proliferation and represent the building blocks of complex mutational processes involving the rearrangement of large genomic regions. These complex genomic rearrangements have functional consequences (e.g., gene fusion formation, inactivation of tumor suppressor) and have been associated with lower survival and poor response to immunotherapy. The patterns of small somatic variants have been well studied and characterized in human cancers. However, the genetic architecture and functional consequences of complex genomic rearrangements, despite their clinical significance, still need to be explored due to algorithmic and technological limitations. Therefore, the aims of this proposal are first to develop novel computational tools to fully characterize the genetic architecture of complex genomic rearrangements and second to study their functional impact on tumor gene expression programs through the lens of a solid theoretical framework. Methodologically, the de novo assembly of genomes is the only approach that allows a complete and unbiased characterization of all genomic alterations. Recently, we developed WENGAN, a new algorithm for the ultrafast, accurate, and complete de novo reconstruction of human genomes combining short and long reads technologies. Initial validation of WENGAN for de novo reconstruction of cancer genomes enabled the discovery of a large degree of tumor genomic reorganization with thousands of SVs. The latter remains elusive when using alternative algorithms and technologies. Therefore, this experience represents a solid foundation for developing this proposal. We will work with the following specific objectives: 1) Develop efficient algorithms to reconstruct haplotype-resolved genomes; 2) combine haplotype-resolved genomes and variation graphs with building complete structural variant maps of tumors; 3) study the functional impact of complex SVs at the single-cell level; and 4) Infer from multi-omic data the tumor tasks (trade-offs) using the multi-task evolution theory. We have assembled a multidisciplinary network of national and international (France and Germany) experts in algorithms, sequencing technologies, and cancer genomics to develop these objectives. Additionally, we compromise the mentoring and training of undergraduate and magister students by offering thesis topics directly related to the proposal's goals. In summary, we propose an approach that integrates the development of new computational algorithms, a solid theoretical framework, and the generation of state-of-the-art multi-omic data to study the genetic architecture and functional impact of large-scale genomic rearrangements in a prevalent Chilean cancer. The project will deliver, in four years, the first haplotype-resolved Chilean genome, the first graph reference of Chilean individuals, and the first multi-omic characterization of a prevalent Chilean cancer.

Center for Mathematical Modeling.

Sediment routing systems link the fate of sediment from source to sink in relation to the processes of sediment generation, transport and storage that take place at or near the surface. The transfer of sediment within the sediment routing system involves a cascade of sediment from erosional source areas to depositional sinks in which sediment connectivity between different compartments of the landscape modulate sediment pathways at different scales of space and time. Fluvial systems and transport of suspended sediment are key elements in the transfer of sediment across landscapes and their workings are being altered by climate change and human intervention. In central Chile (30º-37ºS) a decade-long drought is resulting in reduced water discharge, glacier retreat, and diminished sediment discharge to the ocean. The later reflects changing sediment dynamics within the fluvial basins of this region. In this project the temporal and spatial variability of sediment sources and pathways will be studied in the El Volcán River Basin (33ºS), a mountain catchment tributary to the Maipo River, during two consecutive high runoff periods (October-March; 2022-2023 and 2023-2024), with the goal to evaluate interannual and seasonal variations in sediment connectivity in the El Volcán River Basin by identifying the areas of the basin that feed sediment to the fluvial system and describe which pathways of sediment operate under changing flow conditions. Considering the hydrological and sedimentological regime of the mountain catchments in central Chile, the working hypothesis of this proposal is that sediment connectivity in the fluvial system varies throughout seasons as the flow regime, source of runoff, and sediment sources fluctuate from spring to late summer. The variability of the bedrock geology in this basin provides favorable conditions to use sediment provenance techniques to study sediment production and transfer from source to sink at the seasonal and interannual scale. The investigation will start with a geomorphological analysis of the basin that will allow the identification of potential sediment sources (alluvial fans and cones, scree slopes, gullies, fluvial terraces, landslides, etc), which will be consequently sampled. Suspended sediment will be sampled in different parts of this basin during two seasons of high runoff, from the upper tributaries to the catchment’s outlet. Sediment provenance will be analyzed in all suspended sediment samples in order to track sediment sources and pathways. Geochemistry (major and trace elements) is a widely used method to infer sediment provenance in continental environments. Fallout radionuclides (137Cs, 210Pb) are efficiently fixed in fine sediment particles and their activities are independent of lithology and soil type. Therefore, their activities are different in surficial and subsurface sources as well as in recently exposed land or in zones with variable erosion rates. Geochemistry and fallout radionuclides will be measured in the suspended sediment samples and will be compared to the same properties measured in all potential sediment sources within this basin. The compositional results will be analyzed using mixing models in order to establish the relative contribution of each of the potential sources over time. With the study of sediment provenance at seasonal and interannual scales in the El Volcán River Basin it is expected to i) determine temporal and spatial variation in the sources that supply sediment, and therefore the zones within the basin that produce sediment: low, medium, or high El Volcán River Basin, ii) evaluate the erosion processes of the surface (sheet or reel erosion) or subsurface (stream banks, gullies) that participate in the mobilization of sediment to the river, iii) establish variations in the transfer of the sediment provenance signal in this catchment (cascade of sediment from source to sink), iv) evaluate interannual variability of these processes, and v) build a conceptual model of sediment connectivity in this basin during changing flow conditions. The results of this investigation will provide insights into the processes that modulate sediment transport in the Maipo Basin, which is relevant considering the frequent episodes of high turbidity in this river. Moreover, the results could help to forecast the potential influence of projected hydroclimatic changes and anthropogenic activity in central Chile on particle fluxes across the Andes and resultant morphological and sedimentary adjustment of fluvial basins as the sediment is transferred from mountain source to ocean sink.

During the last decades, compelling evidence shows how the context in which early life takes place impinges risk or protection for later development of non-communicable chronic diseases. In this regard, impaired fetal growth, as occur in the fetal growth restriction (FGR), leads to a higher risk for later cardiovascular diseases, an effect that would be mediated by accelerated aging at molecular, structural, and functional levels. FGR remains a leading cause of perinatal morbidity and mortality, affecting ~10% of pregnancies, but ranging 5 to 25% depending on the nutritional and health conditions of the population surveyed, with a higher prevalence among pregnant women of low socioeconomic status. In the clinic, FGR is normally defined by a fetal weight below the 10th percentile, however, new evidence shows that impaired intrauterine growth may affect several neonates born over the 10th percentile, which may be missed from the perinatal survey for preventing adverse outcomes. This points out the need for further studies to improve the understanding and identification of altered fetal growth trajectories and their consequences on vascular function. Studies in placenta show that FGR vascular dysfunction is also found at birth in chorionic and umbilical arteries. We have demonstrated the presence of functional and molecular markers (e.g. epigenetic changes) of endothelial dysfunction in human umbilical and chorionic vessels, findings that have been further confirmed by comparing systemic (aorta and femoral arteries) and umbilical arteries in animal models of FGR. These traits suggest that umbilical artery endothelial cells (HUAEC) can be used as a surrogate to explore the vascular programming within the fetus, however, their translation to clinical preventive applications for promoting healthy aging deserves further studies. It worth noting that fetal reduced oxygen supply (i.e. fetal hypoxia) and altered blood flow patterns (i.e. shear stress) are key clinical markers in the FGR, independently of the constraints leading to impaired growth, and both factors exert a tight control of vascular development and function across life. However, how these key stimuli interact and impose an epigenetic program on the endothelial function remains elusive. This proposal will focus on the crosstalk between hypoxia and shear stress that results in the endothelial programming related to impaired fetal growth, and the molecular mechanisms that mediate the vascular responses to these stimuli. Furthermore, we will address if these molecular markers may allow detecting early vascular aging in FGR subjects beyond the 10th centile cutoff. We hypothesize that “Impaired fetal growth conditions are associated with epigenetic programming of aging- and mechanosensing-related miRNAs and transcripts in the endothelium, which can be triggered by the confluence of altered flow patterns and hypoxia resulting in molecular and structural pro-hypertensive biomechanical vascular properties”. This hypothesis will be addressed by three General Objectives (GO) involving ex vivo, in vitro, and in vivo observational and mechanistic approaches: GO1 To demonstrate, in HUAEC, whether late FGR results in epigenetic changes related to the regulation of vascular aging and the expression of mechanosensing mechanisms involved in the endothelial-dependent relaxation, and their relationship with general prenatal parameters of vascular health. GO1 will be performed by recruiting HUAEC samples from late FGR and control pregnancies, to assess transcriptomic and DNA methylation analyses that will be crossed with prenatal clinical data. GO2 To study, in vivo, whether stimuli related to FGR (i.e. hypoxia and altered shear stress) differentially regulate mechanosensing pathways involved in the endothelial-dependent relaxation and their relationship with the in vivo and ex vivo vascular properties (e.g. functional and biomechanical). GO2 will be performed in chicken embryos exposed to hypoxia and treated with agents targeting mechanosensing pathways, in which wall shear stress will be determined by Ultrasound Localization Microscopy, with complementary functional, structural, and molecular analyses. GO 3. To study, in cultured HUAEC, whether stimuli related to impaired fetal growth converge in the regulation of mechanosensing-and aging-related transcripts and miRNA, contributing to the cellular programming of endothelial dysfunction. OG3 will be performed in HUAEC exposed, in vitro, to sustained hypoxia and diverse flow patterns (shear stress), in which target DNA methylation, miRNA, transcripts, and proteins will be assessed. Our expected outcome is to improve the knowledge about the endothelial epigenetic programming after FGR and enhance the characterization of in vivo shear stress patterns and mechanisms induced by chronic fetal hypoxia. This project is not only relevant to uncover the developmental approaches for diagnosing and treatments in complicated pregnancies.

El objetivo principal de MIGA (Millenium Institute in Green Ammonia) es consolidar un espacio interdisciplinario de excelencia científica promoviendo la formación de recursos humanos avanzados, conocimiento y tecnología en temas relacionados con la producción sostenible y el uso del amoniaco como vector energético. La misión de MIGA es abordar este desafío con un enfoque interdisciplinario que acorte las brechas tecnológicas actuales, avanzando en el conocimiento y la tecnología, generando capacitación interdisciplinaria en el área para nuevos investigadores, contribuyendo a la instalación de economías basadas en energías limpias para Chile y la comunidad internacional. MIGA es conceptualizado en cinco áreas de investigación interdisciplinarias e interrelacionadas: 1. Producción electroquímica de NH3 2. Producción de H2 a partir de electrólisis de NH3 3. Diseño y prototipos de pilas de combustible de NH3 4. Procesos de corrosión y protección 5. Economía del amoniaco

The project aims to study the cardiac cycle's impact on healthy adults' brain responses and auditory perception. Using electroencephalogram and electrocardiogram recordings, we compare the neuronal responses to heartbeats in response to auditory stimulation in the different phases of the cardiac cycle. We evaluate cardioceptive measures to establish relationships between neuronal activity and sensory and behavioral parameters.