Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

Multi-scale study of the genome architecture and its dynamical facets

High-throughput Chromosome Conformation Capture (3C) techniques have provided a comprehensive overview of the genome architecture. Hi-C, a derivative of 3C, has become a reference technique to study the 3D chromatin structure and its relationship with the functional state of the cell. However, several aspects of the analysis and interpretation of Hi-C data remain a challenge and may hide a potential yet to be unveiled. In this thesis, we explore the structural landscape of multiple chromatin features. We developed an integrative approach combining in situ Hi-C data with nine additional omic layers and revealed a new dynamic and transitional genomic compartment enriched in poised and polycomb-repressed chromatin. This novel intermediate compartment plays an important role in the modulation of the genome during B cells differentiation and upon neoplastic transformation, specifically in chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) patients. We also developed TADpole, a computational tool designed to characterize the hierarchy of topologically-associated domains (TADs) using Hi-C interaction matrices. We demonstrated its technical and biological robustness, and its capacity to reveal topological differences in high-resolution capture Hi-C experiments. El desarrollo de métodos experimentales basados en la captura de la conformación cromosómica (3C) ha permitido tener una visión más detallada de la arquitectura genómica. El Hi-C, derivado del 3C, se ha convertido en una técnica de referencia para analizar la estructura tridimensional de la cromatina, así como su relación con el estado funcional celular. Sin embargo, varios aspectos del análisis y la interpretación de los datos de Hi-C siguen siendo un desafío, y pueden ocultar un potencial aún por descubrir. En esta tesis se exploran múltiples niveles de organización estructural de la cromatina. Hemos realizado un estudio integrativo combinando datos de in situ Hi-C con nueve capas epigenéticas y hemos revelado un nuevo compartimento genómico caracterizado por su dinámica y capacidad de transición, enriquecido en cromatina reprimida por polycomb. Este nuevo compartimento intermedio juega un papel importante en la modulación del genoma durante la diferenciación de células B y durante su transformación neoplásica, específicamente en pacientes con leucemia linfocítica crónica (CLL) o con linfoma de células del manto (MCL). Además, hemos desarrollado TADpole, un nuevo método computacional destinado a la detección de la jerarquía de dominios asociados topológicamente (TADs) empleando mapas de interacciones de Hi-C. Hemos demostrado su robustez ante una evaluación técnica y biológica, así como su capacidad de detectar diferencias topológicas en experimentos de capture Hi-C de alta resolución

Multi-scale study of the genome architecture and its dynamical facets

High-throughput Chromosome Conformation Capture (3C) techniques have provided a comprehensive overview of the genome architecture. Hi-C, a derivative of 3C, has become a reference technique to study the 3D chromatin structure and its relationship with the functional state of the cell. However, several aspects of the analysis and interpretation of Hi-C data remain a challenge and may hide a potential yet to be unveiled. In this thesis, we explore the structural landscape of multiple chromatin features. We developed an integrative approach combining in situ Hi-C data with nine additional omic layers and revealed a new dynamic and transitional genomic compartment enriched in poised and polycomb-repressed chromatin. This novel intermediate compartment plays an important role in the modulation of the genome during B cells differentiation and upon neoplastic transformation, specifically in chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) patients. We also developed TADpole, a computational tool designed to characterize the hierarchy of topologically-associated domains (TADs) using Hi-C interaction matrices. We demonstrated its technical and biological robustness, and its capacity to reveal topological differences in high-resolution capture Hi-C experiments. El desarrollo de métodos experimentales basados en la captura de la conformación cromosómica (3C) ha permitido tener una visión más detallada de la arquitectura genómica. El Hi-C, derivado del 3C, se ha convertido en una técnica de referencia para analizar la estructura tridimensional de la cromatina, así como su relación con el estado funcional celular. Sin embargo, varios aspectos del análisis y la interpretación de los datos de Hi-C siguen siendo un desafío, y pueden ocultar un potencial aún por descubrir. En esta tesis se exploran múltiples niveles de organización estructural de la cromatina. Hemos realizado un estudio integrativo combinando datos de in situ Hi-C con nueve capas epigenéticas y hemos revelado un nuevo compartimento genómico caracterizado por su dinámica y capacidad de transición, enriquecido en cromatina reprimida por polycomb. Este nuevo compartimento intermedio juega un papel importante en la modulación del genoma durante la diferenciación de células B y durante su transformación neoplásica, específicamente en pacientes con leucemia linfocítica crónica (CLL) o con linfoma de células del manto (MCL). Además, hemos desarrollado TADpole, un nuevo método computacional destinado a la detección de la jerarquía de dominios asociados topológicamente (TADs) empleando mapas de interacciones de Hi-C. Hemos demostrado su robustez ante una evaluación técnica y biológica, así como su capacidad de detectar diferencias topológicas en experimentos de capture Hi-C de alta resolución

Three-dimensional genome organization via triplex-forming RNAs

An increasing number of long noncoding RNAs (lncRNAs) have been proposed to act as nuclear organization factors during interphase. Direct RNA-DNA interactions can be achieved by the formation of triplex helix structures where a single-stranded RNA molecule hybridizes by complementarity into the major groove of double-stranded DNA. However, whether and how these direct RNA-DNA associations influence genome structure in interphase chromosomes remain poorly understood. Here we theorize that RNA organizes the genome in space via a triplex-forming mechanism. To test this theory, we apply a computational modeling approach of chromosomes that combines restraint-based modeling with polymer physics. Our models suggest that colocalization of triplex hotspots targeted by lncRNAs could contribute to large-scale chromosome compartmentalization cooperating, rather than competing, with architectural transcription factors such as CTCF.This work was supported by the European Research Council under the 7th Framework Program FP7/2007-2013 (ERC grant agreement no. 609989 to M.A.M.-R.) and the Spanish Ministerio de Ciencia, Innovación y Universidades through nos. IJCI-2015-23352 to I.F. and BFU2017-85926-P and PID2020-115696RB-I00 to M.A.M.-R. CRG acknowledges support from ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208 and the CERCA Program/Generalitat de Catalunya, as well as support from the Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III and the EMBL partnership, the Generalitat de Catalunya through Departament de Salut and Departament d’Empresa i Coneixement, and cofinancing with funds from the European Regional Development Fund by the Spanish Ministry of Science and Innovation corresponding to the Programa Opertaivo FEDER Plurirregional de España 2014–2020 and by the Secretaria d’Universitats i Recerca, Departament d’Empresa i Coneixement of the Generalitat de Catalunya corresponding to the program Operatiu FEDER Catalunya 2014–2020 and the NIH (to C.T. Wu no. R01HD091797 for supporting I.F.

Hierarchical chromatin organization detected by TADpole

Mètodes computacionals; GenòmicaMétodos computacionales; GenómicaComputational Methods; GenomicsThe rapid development of Chromosome Conformation Capture (3C-based techniques), as well as imaging together with bioinformatics analyses, has been fundamental for unveiling that chromosomes are organized into the so-called topologically associating domains or TADs. While TADs appear as nested patterns in the 3C-based interaction matrices, the vast majority of available TAD callers are based on the hypothesis that TADs are individual and unrelated chromatin structures. Here we introduce TADpole, a computational tool designed to identify and analyze the entire hierarchy of TADs in intra-chromosomal interaction matrices. TADpole combines principal component analysis and constrained hierarchical clustering to provide a set of significant hierarchical chromatin levels in a genomic region of interest. TADpole is robust to data resolution, normalization strategy and sequencing depth. Domain borders defined by TADpole are enriched in main architectural proteins (CTCF and cohesin complex subunits) and in the histone mark H3K4me3, while their domain bodies, depending on their activation-state, are enriched in either H3K36me3 or H3K27me3, highlighting that TADpole is able to distinguish functional TAD units. Additionally, we demonstrate that TADpole's hierarchical annotation, together with the new DiffT score, allows for detecting significant topological differences on Capture Hi-C maps between wild-type and genetically engineered mouse.European Research Council under the Seventh Framework Program FP7/2007-2013 [609989, in part]; European Union's Horizon 2020 Research and Innovation Programme [676556]; Spanish Ministry of Science and Innovation [BFU2013-47736-P, BFU2017-85926-P to M.A.M-R., IJCI-2015-23352 to I.F., BES-2014-070327 to P.S-V.]; ‘Centro de Excelencia Severo Ochoa 2013–2017’, SEV-2012-0208; CERCA Programme/Generalitat de Catalunya (to C.R.G.). Funding for open access charge: European Research Council under the Seventh Framework Program FP7/2007-2013 [609989]. We also acknowledge the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208, the CERCA Programme/Generalitat de Catalunya, Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III, the Generalitat de Catalunya through Departament de Salut and Departament d’Empresa i Coneixement and the Co-financing by the Spanish Ministry of Science and Innovation with funds from the European Regional Development Fund (ERDF) corresponding to the 2014-2020 Smart Growth Operating Program to the CRG