Forest biotechnology is a fast emerging field of research. The application of biotechnological tools will enhance the quality of the forest products. The resultant value added and environmentally sustainable products are an absolute necessity in the future. The study of wood biosynthesis and degradation will result in enormous knowledge resources, which can be used for exploiting wood properties. This thesis addresses questions representing both wood degradation and biosynthesis. The wood degrading fungus Phanerochaete chrysosporium is expression profiled with the microarray technology. The objective is to understand the expression pattern of the extracellular carbohydrate active enzymes (CAZymes) secreted by the organism. The data obtained increases our understanding of gene expression upon growth on cellulose. Wood biosynthesis is studied with the model wood forming tree species, Populus. The plentiful data resources from the expression profiling during wood formation in Populus are used as the platform of this work. One of the wood specific genes, PttMAP20, previously with an unknown function is studied in this thesis. The immunolocalisation of PttMAP20 with specific antibodies is demonstrated. The putative microtubule-targeting domain of the protein is demonstrated microscopically and by using a biochemical binding assay. / QC 20101217

Kolorektal cancer (CRC) är en av de vanligaste cancersjukdomarna i världen med cirka 1 miljon nya detekterade fall per år. Special AT-rich sequence-binding protein1 (SATB1) är ett celltyp-specifikt kärnmatrix-associerat DNA-bindande protein, vilket utgörs av AT-rika DNA sekvenser. Det har tidigare demonstrerats att en annan medlem i SATB-familjen, SATB2, uttrycks på ett vävnadsspecifikt sätt i normal mukosa i nedre mag-tarmkanalen och i CRC. β-catenin är en intracellulär mediator i Wnt/β-catenin signaleringsvägen, som spelar en viktig roll i kolorektal carcinogenes. Uttryck av SATB1, SATB2 och β-catenin har studerats i tissue microarrays med tumörprover från 270 CRC patienter. Deras inbördes korrelation samt koppling till recidivfri överlevnad har studerats med hjälp av Spearman´s korrelationstest respektive Kaplan-Meier analys och log-rank test. Resultatet från immunhistokemiska färgningar visar att det finns en korrelation mellan de analyserade markörerna. Därutöver fann vi att SATB1 uttryck är kopplat till kortare recidivfri överlevnad i tumörer med lågt SATB2 uttryck. / Colorectal cancer (CRC) is one of the most common cancers in the world with about 1 million new cases annually. Special AT-rich sequence binding protein 1 (SATB1), is a cell type specific nuclear matrix associated DNA binding protein, which consists of AT-rich DNA sequences. It has previously been demonstrated that another member in SATB-family, SATB2, is expressed in a tissue-specific manner in normal mucosa in the lower gastrointestinal tract and in CRC. β-catenin is an intracellular mediator of the Wnt/ β-catenin signaling pathway and plays an important role in colorectal carcinogenesis. Expression of SATB1, SATB2 and β-catenin was analyzed in tissue microarrays with tumors from 270 CRC patients. Spearman´s correlation test was used to assess the correlations and the impact of SATB1 and SATB2 on recurrence free survival was assessed by Kaplan-Meier analysis and log-rank test. The result of immunohistochemical staining shows that there is a correlation between the analyzed markers and that SATB1 expression is a poor prognostic factor in tumors expressing low levels of SATB2.

Gene duplications can facilitate genetic innovation, reduce pleiotropy and catalyze reproductive incompatibilities and speciation. Therefore, the molecular and transcriptional fate of duplicate genes plays an important role in the evolutionary trajectory of entire genomes and transcriptomes. Using the polyploid African clawed frog Xenopus, I have investigated mechanisms that promote the retained expression of duplicate genes (paralogs) after whole genome duplication. The studies herein estimated molecular evolution and characterized expression divergence of thousands of duplicate genes and a singleton ortholog from a diploid outgroup. In this thesis, I have discussed the multiple mechanisms for the retention of duplicate genes in a polyploid genome and examined the potential effects that gene characteristics before duplication have on the odds of duplicate gene persistence. I have also explored the use of microarrays for comparative transcriptomics between duplicate genes, and between diverged genomes. The main objectives of my thesis were to better understand the genetic mechanisms that promote the retained expression of gene duplicates. My research utilized the duplicated genome from the allopolyploid clawed frog Xenopus. Genome duplication in clawed frogs offers a compelling opportunity to study factors that influence the genetic fates of gene duplicates because many paralogs in these frogs are of the same age, permitting one to control for the influence of time when evaluating the impact of duplication. My work has major impacts on several biological fronts including evolutionary genomics and comparative transcriptomics, and also on technical aspects of using microarrays. I have provided among the most comprehensive studies of its kind, in terms of examining molecular and regulatory aspects of thousands of expressed duplicates of the same age, and exploring various alternative hypotheses to explain how these genes are retained. / Thesis / Doctor of Philosophy (PhD)

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<p>Fabrication of microarrays using sol-gel immobilization has been utilized as an approach to develop high density biosensors. Microarray fabrication using various printing techniques including pin-printing and piezoelectric ink jet printing methods has been demonstrated. However, only limited characterization to understand the encapsulated biomolecule-material interface has been reported. Herein, Chemical characterization using X-ray photoelectron spectroscopy (XPS) and infrared spectroscopy (IR) on pin-printed microarrays of sol-gel derived acetylcholinesterase (AChE) microarrays is reported. Furthermore, the <em>in situ</em> fabrication of microarrays following the sol-gel process using piezoelectric ink jet printing methods was explored. Through techniques measuring solution viscosity, surface tension and particle size, important aspects of bio-ink formulation for piezoelectric ink jet printing were identified. Combined, a greater understanding towards the fabrication and characterization of sol-gel derived microarrays was achieved through this exploratory research.</p> / Master of Science (MSc)

La transcriptómica estudia el nivel de expresión de los genes en distintas condiciones experimentales para tratar de identificar los genes asociados a un fenotipo dado así como las relaciones de regulación entre distintos genes. Los datos ómicos se caracterizan por contener información de miles de variables en una muestra con pocas observaciones. Las tecnologías de alto rendimiento más comunes para medir el nivel de expresión de miles de genes simultáneamente son los microarrays y, más recientemente, la secuenciación de RNA (RNA-seq). Este trabajo de tesis versará sobre la evaluación, adaptación y desarrollo de modelos estadísticos para el análisis de datos de expresión génica, tanto si ha sido estimada mediante microarrays o bien con RNA-seq. El estudio se abordará con herramientas univariantes y multivariantes, así como con métodos tanto univariantes como multivariantes. / Tarazona Campos, S. (2014). Statistical methods for transcriptomics: From microarrays to RNA-seq [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/48485 / Premios Extraordinarios de tesis doctorales

Yes / A new class of material resistant to bacterial attachment has been discovered that is formed from polyacrylates with hydrocarbon pendant groups. In this study, the relationship between the nature of the hydrocarbon moiety and resistance to bacteria is explored, comparing cyclic, aromatic, and linear chemical groups. A correlation is shown between bacterial attachment and a parameter derived from the partition coefficient and the number of rotatable bonds of the materials' pendant groups. This correlation is applicable to 86% of the hydrocarbon pendant moieties surveyed, quantitatively supporting the previous qualitative observation that bacteria are repelled from poly(meth)acrylates containing a hydrophilic ester group when the pendant group is both rigid and hydrophobic. This insight will help inform and predict the further development of polymers resistant to bacterial attachment. / Wellcome Trust (grant number 085245) and EMRP (IND56)

L’émergence des Mégadonnées (« Big Data ») en biologie moléculaire, surtout à travers la transcriptomique, a révolutionné la façon dont nous étudions diverses disciplines telles que le processus de développement du médicament ou la recherche sur le cancer. Ceci fut associé à un nouveau concept, la médecine de précision, dont le principal but est de comprendre les mécanismes moléculaires entraînant une meilleure réponse thérapeutique chez le patient. Cette thèse est à mi-chemin entre les études pharmaco — et toxicogénomiques expérimentales, et les études cliniques et translationnelles. Le but de cette thèse est surtout de montrer le potentiel et les limites de ces jeux de données et leur pertinence pour la découverte de biomarqueurs de réponse ainsi que la compréhension des mécanismes d’action/toxicité de médicaments, en vue d’utiliser ces informations à des fins thérapeutiques. L’originalité de cette thèse réside dans son approche globale pour analyser les plus larges jeux de données pharmaco/toxicogénomiques publiés à ce jour et ceci pour : 1) Aborder la notion de biomarqueurs de réponse aux médicaments en pharmacogénomique du cancer, en étudiant les facteurs discordants entre deux grandes études publiées en 2012; 2) Comprendre le mécanisme d’action des médicaments et construire une taxonomie performante en utilisant une approche intégrative; et 3) Créer un répertoire toxicogénomique à partir des hépatocytes humains, exposés à différentes classes de médicaments et composés chimiques. Mes contributions principales sont les suivantes : • J’ai développé une approche bioinformatique pour étudier les facteurs discordants entre deux grandes études pharmacogénomiques et suggérées que les différences observées émergeaient plutôt de l’absence de standardisation des mesures pharmacologiques qui pourrait limiter la validation de biomarqueurs de réponse aux médicaments. • J’ai implémenté une approche bioinformatique qui montre la supériorité de l’intégration tenant en compte des différents paramètres pour les médicaments (structure, cytotoxicité, perturbation du transcriptome) afin d’élucider leur mécanisme d’action (MoA). • J’ai développé un pipeline bioinformatique pour étudier le niveau de conservation des mécanismes moléculaires entre les études toxicogénomiques in vivo et in vitro démontrant que les hépatocytes humains sont un modèle fiable pour détecter les produits toxiques hépatocarcinogènes. Au total, nos études ont permis de fournir un cadre de travail original pour l’exploitation de différents types de données transcriptomiques pour comprendre l’impact des produits chimiques sur la biologie cellulaire. / The emergence of Big Data in molecular biology, especially through the study of transcriptomics, has revolutionized the way we look at various disciplines, such as drug development and cancer research. Big data analysis is an important part of the concept of precision medicine, which primary purpose is to understand the molecular mechanisms leading to better therapeutic response in patients. This thesis is halfway between pharmaco-toxicogenomics experimental studies, and clinical and translational studies. The aim of this thesis is mainly to show the potential and limitations of these studies and their relevance, especially for the discovery of drug response biomarkers and understanding the drug mechanisms (targets, toxicities). This thesis is an original work since it proposes a global approach to analyzing the largest pharmaco-toxicogenomic datasets available to date. The key aims were: 1) Addressing the challenge of reproducibility for biomarker discovery in cancer pharmacogenomics, by comparing two large pharmacogenomics studies published in 2012; 2) Understanding drugs mechanism of action using an integrative approach to generate a superior drug-taxonomy; and 3) Evaluating the conservation of toxicogenomic responses in primary hepatocytes vs. in vivo liver samples in order to check the feasability of cell models in toxicology studies. My main contributions can be summarized as follow: - I developed a bioinformatics pipeline to study the factors that trigger (in)consistency between two major pharmacogenomic studies. I suggested that the observed differences emerged from the non-standardization of pharmacological measurements, which could limit the validation of drug response biomarker. - I implemented a bioinformatics pipeline that demonstrated the superiority of the integrative approach, since it takes into account different parameters for the drug (structure, cytotoxicity, transcriptional perturbation) to elucidate the mechanism of action (MoA). - I developed a bioinformatics pipeline to study the level of conservation of toxicity mechanisms between the in vivo and in vitro system, showing that human hepatocytes is a reliable model for hepatocarcinogens testing. Overall, our studies have provided a unique framework to leverage various types of transcriptomic data in order to understand the impact of chemicals on cell biology.