Ciencias Exactas y Ciencias de la Salud
Permanent URI for this collectionhttps://hdl.handle.net/11285/551014
Pertenecen a esta colección Tesis y Trabajos de grado de los Doctorados correspondientes a las Escuelas de Ingeniería y Ciencias así como a Medicina y Ciencias de la Salud.
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- Design and characterization of a biosensor for the detection of codon-readthrough inducers(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025-02-28) Trejo Alarcón, Luisa María; Licona Cassani, Cuauhtémoc; emipsanchez; Utrilla Carreri, José; García Echauri, Sergio A.; Rodríguez López, Carlos Eduardo; García García, Jorge Donato; Escuela de Ingeniería y Ciencias; Campus Monterrey; Cruz Morales, PabloLas enfermedades raras afectan a menos del 0.05% de la población mundial y se atribuyen en gran medida a desórdenes genéticos que generan proteínas incompletas. Los inductores de codon-readthrough (CR), como algunos aminoglucósidos (AGs), han sido evaluados como terapias potenciales debido a su capacidad para restaurar la traducción de genes afectados. En este trabajo, desarrollamos un biosensor eficiente basado en levaduras para la detección de moléculas con actividad CR. Construimos una cepa de Saccharomyces cerevisiae con un plásmido conteniendo el gen reportero de luminiscencia nluc modificado para incluir un codón de terminación prematura (PTC), lo que lo hace no funcional. La actividad CR, inducida por AGs comerciales como G418, gentamicina, tobramicina y paromomicina, restauran la funcionalidad del gen, generando una señal de luminiscencia en ensayos in vivo en microplaca. El sistema fue aplicado al análisis de 91 cepas de actinobacterias aisladas, identificando un potencial inductor de CR, proveniente de la cepa Streptomyces sp. CR101A. A través de minería genómica, fraccionamiento por Cromatografía Líquida de Ultra Alta Resolución (UPLC) y espectrometría de masas (MS), se identificó un clúster de genes biosintéticos (BGC) como responsable de la producción de una molécula con un anillo ciclitol. Actualmente, se trabaja con herramientas de biología sintética como CRISPR/Cas9 para la generación de mutantes y expresión heteróloga, para confirmar la implicación del BGC detectado en la producción del inductor de CR.
- Insights from colostrum multi-omics: exploring bioactive co-occurrence patterns in the context of maternal obesity(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2024-06-13) Gámez Valdez, July Stephany; Licona Cassani, Cuauhtémoc; emimmayorquin; Brunck, Marion Emilie Genevieve; Lara Díaz, Víctor Javier; Gutiérrez García, Karina; Mancilla Herrera, Ismael; Escuela de Ingeniería y Ciencias; Campus MonterreyBreastmilk is a complex and dynamic fluid that supplies hydration, nutrients, and bioactives essential for the optimal growth and development of neonates. Breastmilk bioactives play pivotal roles in providing passive immunity against pathogens, fostering tolerance to nascent microbiota, and facilitating the maturation of the intestinal system. Maternal obesity, a significant health concern, has been linked to changes in breastmilk composition. Understanding the intricate dynamics of bioactive compounds in breastmilk. While previous research has often focused on analyzing individual breastmilk constituents separately, there is a growing recognition of the need for a more holistic approach that considers the systemic nature of breast milk. Specifically, investigating the interactions among different bioactives, such as microbiota and metabolites, is crucial for comprehending the overall composition and function of breastmilk. Colostrum, serving as the initial seed for neonatal gut microbiota establishment, holds particular significance in this context. Nonetheless, our current comprehension of how maternal obesity impacts breastmilk bioactives through a systems biology perspective is limited. This doctoral thesis aims to bridge this gap by examining the influence of maternal obesity on the co-occurrence patterns of colostrum bioactives, including microbiota, metabolites, and pro-inflammatory cytokines. Through collaboration with the Hospital Regional de Alta Especialidad Materno Infantil, we obtained two cohorts of volunteers from Monterrey, comprising 30 and 48 participants, respectively, who generously provided colostrum samples. These cohorts were sampled at different times, one from May to December 2019 and the other from October 2020 to July 2022. Samples were categorized into two groups based on BMI, classified according to the World Health Organization as normal weight (≤ 24.9 kg/m2) or obesity (≥ 30 kg/m2). Using co-occurrence networks and multi-omics approaches, specifically 16S-microbiota profiling, and untargeted metabolomics, we explored the compositional and structural changes within the colostrum ecosystem in the context of maternal obesity. Our study reveals that maternal obesity induces alterations in the ecosystem structure of colostrum. While normal weight conditions showed more positive correlations between pro-inflammatory cytokines and Proteobacteria members, such as Neisseriaceae, Pasteurellaceae, and Enterobacteriaceae, these correlations were absent in obesity samples. Microbiota diversity remained stable, with subtle shifts like reduced Proteobacteria abundance observed in colostrum from women with obesity. Furthermore, metabolite profile, particularly 15-HEDE, a lipid mediator involved in pro-inflammatory response, vasodilation and hyperpermeability, exhibited reduced abundances in response to maternal obesity, also show intricate associations with inflammatory-related cytokines (IL-12p70 and IL-10) and microbial taxa (Beijerinckiaceae and Burkholderiaceae). Additionally, our study highlights the importance of considering neonate sex bias in breastmilk microbiota research, as it influences the prevalence of specific bacteria such as Streptococcaceae, Xanthobacteraceae, and Burkholderiaceae. These findings underscore the connection between alterations in the bacterial community, metabolites, and inflammatory markerswithin the colostrum environment in the context of maternal obesity. Further research is necessary to elucidate the interactions between the host and bioactives in colostrum and their broader implications concerning maternal obesity.
- Pan-genomic epidemiology of tuberculosis: dnraveling the genetic diversity of mycobacterium tuberculosis clinical isolates(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2023-11-06) Mejía Ponce, Paulina Mayell; Licona Cassani, Cuauhtémoc; emimmayorquin; Zenteno Cuevas, Roberto; Sélem Mojica, Nelly; Treviño Alvarado, Víctor Manuel; Enciso Moreno, José Antonio; Rodríguez López, Carlos Eduardo; Escuela de Ingeniería y Ciencias; Campus MonterreyGenomic epidemiology has significantly advanced our understanding of tuberculosis (TB) by providing standards to define sub-lineages, drug resistance patterns, and transmission groups (TGs). However, this approach has its limitations, primarily its reliance on a single reference genome, which fails to capture valuable genetic information present in diverse Mycobacterium tuberculosis complex (MTBC) lineages. Moreover, the underrepresentation of specific geographical regions, notably Mexico, in defining these standards has hindered the identification of region-specific disease markers. In this study, we embark on a comprehensive exploration of the genetic diversity of MTBC across regions, sub-lineages, and TGs, marking a shift from genomic epidemiology to pan-genomic epidemiology in TB research. Our research unfolds across three distinct sections, each addressing a critical facet of our overarching project. First, we contribute to an extended dataset of Mycobacterium tuberculosis (Mtb) clinical isolates from TB patients in various Mexican states, utilizing a whole-genome sequencing (WGS)-based strategy (Chapter 2). We illustrate the distribution of sub-lineages and drug resistance patterns in the country, revealing significant disparities between phenotypic and genotypic drug resistance profiles. In the subsequent section (Chapter 3), we present the groundbreaking discovery of TGs across different Mexican states and identify the primary risk factors associated with these groups. These findings underscore the urgency of enhancing national TB surveillance and monitoring in Mexico, ultimately aiding in the effective management of the disease. In the third and final section of our study (Chapter 4), we broaden our perspective, transitioning from a genomic to a pan-genomic approach. We compile the most extensive MTBC pangenome to date, encompassing 7,034 Mtb genomes from diverse global locations. This comprehensive analysis deciphers the structure of the Mtb pangenome and uncovers specific genes associated with unique traits. Our study addresses the intricate landscape of TB, providing novel insights into genetic diversity, transmission dynamics, and innovative approaches to comprehending this persistent global health challenge