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    • Marzo 2022
    AdjudicadoAgencia Nacional de Investigación y Desarrollo - ANID

    Assessing the resilience of mediterranean-type ecosystems of Chile to projected drought conditions: a multi-scale approach

    [vc_section el_class="container mx-auto align-items-center circle--pattern" css=".vc_custom_1648956589196{padding-top: 3rem !important;}"][vc_row el_class="pb-5"][vc_column][vc_wp_custommenu nav_menu="6"][uoh_breadcrumb_component automatic_breadcrumb="true"][uoh_title_component title_dropdown="big" title_decorator="true"]{{title}}[/uoh_title_component][vc_column_text css=""]Anthropogenic climate change (global change) has caused widespread negative impacts on the vitality and natural dynamics of forest ecosystems across different biomes worldwide. Such impacts are forecast to continue throughout the 21st Century, with Mediterranean-type ecosystems (MTE) being one of the most vulnerable worldwide. MTE are a global conservation priority owing to their high biodiversity, endemism and, carbon and water cycling. In particular, there are significant concerns and uncertainties about the future of tree-dominated MTEs given their vulnerability to global change and, therefore, the consequent likelihood of rapid changes in species distribution. I will assess the response and adaptation of the only Mediterranean forest ecosystems in South America to current and forecasted climate change along biogeographic gradients from sclerophyllous forest to relict mountain in central Chile, using a multi-scale approach, from shrubs to tall trees, and from seeds to ecosystem. This information will allow us to understand the stability of the trailing edge and the potential threats due to the upward migration of other species under global warming in Chilean MTE forest. To achieve these goals, I will exploit multidisciplinary approaches based on hydrology, remote sensing, dendrochronology, ecology, genetic and plant physiology, combining field, laboratory and experimental studies, with the purpose of forecasting forest. Considering that climate change is expected to drive abrupt nonlinear changes throughout the 21st century. I will include analytical approaches that can accommodate these non-linear relationships such as process-based models, non-stationary time-series models and structural equation modeling, as they can support a physiological approach that can robustly assess the forest productivity responses to future climate variability. This proposal will involve three approaches to forecasting forest resilience at different ecological scales: (i) forest-scale research to assess and predict canopy decline and change in foliar phenology using remote sensing and model-based climatic projections using in situ and ex situ data (Obj 1); population-based study assessing the current and future resilience of tree populations using demographic rates, ecophysiological indicators and genetic traits (Obj 2); regeneration-based study to investigate mechanisms of local adaptation in early life stages and potential for persistence of populations, using plant-growth chambers to simulate current and future climate condition in Chile’s MTE (Obj 3). Finally, a multivariate analysis to determine the relative resilience of forests based on information of three previous approach will be assess (Objective 4). Each projected approach will be transformed to predict change percentage, and thus, forecasted resilience rate by short-intermediate (2030-2065) and long term (2065-2100), considering the same weight of each approach. This proposal is a pioneer in global change research in ecology and biogeography due to its focus on possible migration from sclerophyllous trees to mountain forest in South American MTE. Findings will enable us to identify and predict species- and population-level resilience in the face of global climate change to inform priorities for conservation, mitigation and adaptation.[/vc_column_text][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649209804184{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5"][vc_row el_class="container mx-auto align-items-center p-md-0 pt-5"][vc_column el_class="p-0"][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649210787516{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5 pb-md-5"][vc_row el_class="container mx-auto align-items-center"][vc_column][/vc_column][/vc_row][/vc_section]
    Investigador/a Responsable
    • FOVI240153
    • Marzo 2022 - Febrero 2026
    AdjudicadoAgencia Nacional de Investigación y Desarrollo - ANID

    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.
    Co-Investigador/a
      • Marzo 2022 - Diciembre 2029
      AdjudicadoAgencia Nacional de Investigación y Desarrollo - ANID

      Centro de Modelamiento Matemático

      [vc_section el_class="container mx-auto align-items-center circle--pattern" css=".vc_custom_1648956589196{padding-top: 3rem !important;}"][vc_row el_class="pb-5"][vc_column][vc_wp_custommenu nav_menu="6"][uoh_breadcrumb_component automatic_breadcrumb="true"][uoh_title_component title_dropdown="big" title_decorator="true"]{{title}}[/uoh_title_component][vc_column_text css=""]El Centro de Modelamiento Matemático (CMM) es un centro científico líder en Chile para la investigación y aplicaciones de las matemáticas. Fue inaugurado en abril del 2000 y forma parte de la Facultad de Ciencias Físicas y Matemáticas (FCFM) de la Universidad de Chile, en la que se encuentra la principal y más antigua escuela de ingeniería del país. Su objetivo es crear nuevas matemáticas y utilizarlas para resolver problemas provenientes de otras ciencias, la industria y las políticas públicas.[/vc_column_text][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649209804184{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5"][vc_row el_class="container mx-auto align-items-center p-md-0 pt-5"][vc_column el_class="p-0"][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649210787516{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5 pb-md-5"][vc_row el_class="container mx-auto align-items-center"][vc_column][/vc_column][/vc_row][/vc_section]
      Co-Investigador/a
      • Marzo 2022 - Diciembre 2029
      AdjudicadoAgencia Nacional de Investigación y Desarrollo - ANID

      Centro de Modelamiento Matemático

      [vc_section el_class="container mx-auto align-items-center circle--pattern" css=".vc_custom_1648956589196{padding-top: 3rem !important;}"][vc_row el_class="pb-5"][vc_column][vc_wp_custommenu nav_menu="6"][uoh_breadcrumb_component automatic_breadcrumb="true"][uoh_title_component title_dropdown="big" title_decorator="true"]{{title}}[/uoh_title_component][vc_column_text css=""]El Centro de Modelamiento Matemático (CMM) es un centro científico líder en Chile para la investigación y aplicaciones de las matemáticas. Fue inaugurado en abril del 2000 y forma parte de la Facultad de Ciencias Físicas y Matemáticas (FCFM) de la Universidad de Chile, en la que se encuentra la principal y más antigua escuela de ingeniería del país. Su objetivo es crear nuevas matemáticas y utilizarlas para resolver problemas provenientes de otras ciencias, la industria y las políticas públicas.[/vc_column_text][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649209804184{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5"][vc_row el_class="container mx-auto align-items-center p-md-0 pt-5"][vc_column el_class="p-0"][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649210787516{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5 pb-md-5"][vc_row el_class="container mx-auto align-items-center"][vc_column][/vc_column][/vc_row][/vc_section]
      Co-Investigador/a
      • Marzo 2022 - Diciembre 2029
      AdjudicadoAgencia Nacional de Investigación y Desarrollo - ANID

      Centro de Modelamiento Matemático

      [vc_section el_class="container mx-auto align-items-center circle--pattern" css=".vc_custom_1648956589196{padding-top: 3rem !important;}"][vc_row el_class="pb-5"][vc_column][vc_wp_custommenu nav_menu="6"][uoh_breadcrumb_component automatic_breadcrumb="true"][uoh_title_component title_dropdown="big" title_decorator="true"]{{title}}[/uoh_title_component][vc_column_text css=""]El Centro de Modelamiento Matemático (CMM) es un centro científico líder en Chile para la investigación y aplicaciones de las matemáticas. Fue inaugurado en abril del 2000 y forma parte de la Facultad de Ciencias Físicas y Matemáticas (FCFM) de la Universidad de Chile, en la que se encuentra la principal y más antigua escuela de ingeniería del país. Su objetivo es crear nuevas matemáticas y utilizarlas para resolver problemas provenientes de otras ciencias, la industria y las políticas públicas.[/vc_column_text][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649209804184{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5"][vc_row el_class="container mx-auto align-items-center p-md-0 pt-5"][vc_column el_class="p-0"][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649210787516{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5 pb-md-5"][vc_row el_class="container mx-auto align-items-center"][vc_column][/vc_column][/vc_row][/vc_section]
      Co-Investigador/a
      • Marzo 2022 - Febrero 2025
      En Ejecución

      Commutation principles and some variational problems involving spectral sets and functions on various invariant systems

      [vc_section el_class="container mx-auto align-items-center circle--pattern" css=".vc_custom_1648956589196{padding-top: 3rem !important;}"][vc_row el_class="pb-5"][vc_column][vc_wp_custommenu nav_menu="6"][uoh_breadcrumb_component automatic_breadcrumb="true"][uoh_title_component title_dropdown="big" title_decorator="true"]{{title}}[/uoh_title_component][vc_column_text css=""]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.[/vc_column_text][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649209804184{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5"][vc_row el_class="container mx-auto align-items-center p-md-0 pt-5"][vc_column el_class="p-0"][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649210787516{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5 pb-md-5"][vc_row el_class="container mx-auto align-items-center"][vc_column][/vc_column][/vc_row][/vc_section]
      Investigador/a Responsable
      • Marzo 2022
      En EjecuciónAgencia Nacional de Investigación y Desarrollo - ANID

      Nuevos métodos computacionales para caracterizar la arquitectura genética de reordenamientos genómicos complejos en cánceres Chilenos

      [vc_section el_class="container mx-auto align-items-center circle--pattern" css=".vc_custom_1648956589196{padding-top: 3rem !important;}"][vc_row el_class="pb-5"][vc_column][vc_wp_custommenu nav_menu="6"][uoh_breadcrumb_component automatic_breadcrumb="true"][uoh_title_component title_dropdown="big" title_decorator="true"]{{title}}[/uoh_title_component][vc_column_text css=""]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.[/vc_column_text][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649209804184{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5"][vc_row el_class="container mx-auto align-items-center p-md-0 pt-5"][vc_column el_class="p-0"][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649210787516{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5 pb-md-5"][vc_row el_class="container mx-auto align-items-center"][vc_column][/vc_column][/vc_row][/vc_section]
      Investigador/a Responsable
      • 1221029
      • Marzo 2022 - Marzo 2026
      En EjecuciónAgencia Nacional de Investigación y Desarrollo - ANID

      New computational algorithms to elucidate the genetic architecture and functional impact of large-scale rearrangement in prevalent Chilean cancers.

      [vc_section el_class="container mx-auto align-items-center circle--pattern" css=".vc_custom_1648956589196{padding-top: 3rem !important;}"][vc_row el_class="pb-5"][vc_column][vc_wp_custommenu nav_menu="6"][uoh_breadcrumb_component automatic_breadcrumb="true"][uoh_title_component title_dropdown="big" title_decorator="true"]{{title}}[/uoh_title_component][vc_column_text css=""]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.[/vc_column_text][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649209804184{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5"][vc_row el_class="container mx-auto align-items-center p-md-0 pt-5"][vc_column el_class="p-0"][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649210787516{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5 pb-md-5"][vc_row el_class="container mx-auto align-items-center"][vc_column][/vc_column][/vc_row][/vc_section]
      Investigador/a Responsable
      • Marzo 2022 - Marzo 2032
      En EjecuciónAgencia Nacional de Investigación y Desarrollo - ANID

      CUARTO CONCURSO NACIONAL DE FINANCIAMIENTO BASAL PARA CENTROS CIENTÍFICOS Y TECNOLÓGICOS DE EXCELENCIA – PIA: Center for Mathematical Modeling.

      [vc_section el_class="container mx-auto align-items-center circle--pattern" css=".vc_custom_1648956589196{padding-top: 3rem !important;}"][vc_row el_class="pb-5"][vc_column][vc_wp_custommenu nav_menu="6"][uoh_breadcrumb_component automatic_breadcrumb="true"][uoh_title_component title_dropdown="big" title_decorator="true"]{{title}}[/uoh_title_component][vc_column_text css=""]Center for Mathematical Modeling.[/vc_column_text][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649209804184{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5"][vc_row el_class="container mx-auto align-items-center p-md-0 pt-5"][vc_column el_class="p-0"][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649210787516{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5 pb-md-5"][vc_row el_class="container mx-auto align-items-center"][vc_column][/vc_column][/vc_row][/vc_section]
      Co-Investigador/a
      • Marzo 2022
      En EjecuciónAgencia Nacional de Investigación y Desarrollo - ANID

      Linchamientos y Cultura Jurídica Popular en Chile

      [vc_section el_class="container mx-auto align-items-center circle--pattern" css=".vc_custom_1648956589196{padding-top: 3rem !important;}"][vc_row el_class="pb-5"][vc_column][vc_wp_custommenu nav_menu="6"][uoh_breadcrumb_component automatic_breadcrumb="true"][uoh_title_component title_dropdown="big" title_decorator="true"]{{title}}[/uoh_title_component][vc_column_text css=""]Materia Específica: El proyecto busca comprender la conciencia jurídica de los legos que respaldan los linchamientos y, de ser pertinente, dar cuenta de la configuración de alienación legal que atraviesa dicha conciencia jurídica.[/vc_column_text][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649209804184{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5"][vc_row el_class="container mx-auto align-items-center p-md-0 pt-5"][vc_column el_class="p-0"][/vc_column][/vc_row][/vc_section][vc_section css=".vc_custom_1649210787516{background-color: #f6faff !important;}" el_class="p-md-0 pt-md-5 pb-md-5"][vc_row el_class="container mx-auto align-items-center"][vc_column][/vc_column][/vc_row][/vc_section]
      Investigador/a Responsable