Proyectos

[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=""].[/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]

[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=""].[/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]

[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=""]Antimicrobial resistance (AMR) is a phenomenon that happens when bacteria become tolerant to antibiotics used to treat the infections they cause. Antibiotics are key therapeutic tools to treat many human and animal infectious diseases; consequently, keeping their activity on bacteria is fundamental for public and animal health. Aquaculture farming is known for using large amounts of antibiotics, making this activity particularly relevant in development and spread of AMR in aquatic environments. There is evidence in Chile that aquaculture activity increases the presence of resistant bacteria and their corresponding genes in marine sediments directly impacted by salmon farms; however, these evaluations are limited to few locations which hampers a generalization of these conclusions to other salmon farming sites in Chilean waters. There is also evidence suggesting that aquaculture-associated resistance genes present in marine sediments might be transferred to bacteria with pathogenic potential in humans such as Escherichia coli, but no studies have reported the presence of resistance traits in such bacteria in the marine environment from areas impacted by salmon farming in Chile. In countries like Norway, bivalve mollusks are used to monitor antibiotic resistance in Enterobacteria in the marine environment; therefore, they could also be useful for monitoring AMR associated with salmon farming and other anthropogenic sources in Chile. Sampling of bivalve mollusks represents an important logistical advantage to complex and expensive seabed sediment sampling. Los Lagos is the region with the highest historical production of farmed salmon in Chile; then, it is a suitable area to investigate the impact of aquaculture-sourced AMR in the marine environment. The general objective of this proposal is to investigate aquaculture-associated AMR in the marine environment of Los Lagos region from an epidemiologic approach, using bivalve mollusks as sentinel organisms and E. coli as the indicator bacterium. Specific objectives include: 1) to detect, characterize and estimate the prevalence of AMR in E. coli isolated from bivalve mollusks in the Los Lagos region, through a region-level sampling; 2) to study the spatial variability of AMR in E. coli isolated from bivalve mollusks from Los Lagos region; 3) to evaluate the effect of salmon farming activity on the richness and intensity of AMR in E. coli isolated from bivalves from Los Lagos region, controlling for potential confounding factors; and 4) to determine whether significant differences exist in the accumulation of E. coli and resistant E. coli in bivalve mollusks between the sampled bivalve species, accounting for environmental and biological factors. Bivalve mollusks samples will be obtained the 130 sampling stations set along the coast of Los Lagos by the National Program for Surveillance and Control of Harmful Algal Blooms Intoxications (red tides) coordinated by the Ministry of Health. Thirty-three additional sampling stations will be set in the same study area in order to achieve the calculated total sample size of 163 sampling stations. At each sampling station bivalve mollusks will be sampled to quantify E. coli and to detect and characterize both phenotypic and genotypic AMR in this bacterium. The study will be focused in 29 antimicrobial resistance genes (ARGs) and 20 antibiotics commonly used in salmon farming or for which resistance has been detected in previous studies. The antimicrobial susceptibility will be performed by estimating the minimal inhibitory concentrations (MICs) for each antibiotic using the VITEK2 technology. The genotypic analysis will be carried out by means of the detection target ARGs, through PCR. Spatial clustering will be examined for each antibiotic tested using MIC values and the ARG richness index; global clustering will be evaluated through the Moran’s I statistic, while local clustering will be examined by means of the spatial scan statistic. ARG richness will be modeled as a function of the local salmon farming intensity expressed as the number of active salmon farms within 10 km seaway distance from the bivalve sampling location, using a Poisson mixed-effects model in order to control for other AMR sources and important environmental variables. Similar models will be constructed using MICs as the outcome for antimicrobials that show substantial variability in this parameter. Finally, the abundance of both total and resistant E. coli (MPN/100g) found in bivalve mollusks will be modeled as a function of the bivalve species sampled, accounting for bivalve size, water temperature, local salmon farming intensity and distance to other AMR sources, using a mixed-effect linear regression model. This study will contribute to characterize and to identify the main drivers of the environmental AMR in an area with intense salmon farming activity, and it will help to understand how this AMR can impact public health through potential pathogenic bacteria. In practice, this proposal will be the first extensive epidemiological study in this matter in Chile. Moreover, this proposal will help to determine which bivalve mollusks species are suitable to monitor AMR in environments impacted by salmon farming. All this information will be crucial to set the foundations for a future AMR monitoring program in areas of intense aquaculture.[/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]

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.

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.

[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 proyecto tiene como propósito comprender cómo las prácticas artísticas de mediación son un aporte para abordar problemáticas socioculturales y generar estrategias para implementar dichas prácticas en diversos contextos y comunidades del país, expandiendo el rol social de las artes. Su ejecución esta contemplada en cuatro regiones del país y en Barcelona, España, a través de diferentes casos de estudio y un acucioso trabajo de campo.[/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]

[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=""][/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]

[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]

[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=""]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.[/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]