849 research outputs found

    Investigating alternative life history trajectories in two species of Edwardsiid sea anemones using ecological, transcriptomic, and molecular approaches

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    Life histories unfold within the ecological context of an organism's environment, and thus are intimately linked to organismal fitness. The evolution of alternate life history strategies, either within or between taxa, can profoundly affect ontogeny, ecology, and population dynamics. Many cnidarians (sea anemones, corals, jellyfish, etc.) exhibit complex life histories involving sexual reproduction and multiple modes of asexual reproduction. Sea anemones of the family Edwardsiidae exemplify this complexity, and are therefore an attractive system for studying the developmental and ecological ramifications of life history evolution. I used intra- and interspecific comparisons of two Edwardsiid anemones, Edwardsiella lineata, and Nematostella vectensis to investigate alternative life histories using a multifaceted approach that included field-based ecological surveys, functional genetics, transcriptomics, and phylogenetics. Both anemones are capable of sexual and asexual reproduction. N. vectensis produces a rapidly maturing direct developing larva. By contrast, E. lineata has evolved a new larval stage that parasitizes the ctenophore, Mnemiopsis leidyi. Through fieldwork surveys and laboratory culture, I documented several life history traits, such as a previously un-characterized, pre-parasitic larval stage, and the developmental dynamics of early-stage parasitic infections, that augmented gaps in our knowledge of E. lineata's life history. To better understand how and when E. lineata evolved its novel, parasitic life history, I worked with collaborators in the Finnerty lab to sequence, assemble and annotate the transcriptome. Through a multigene molecular clock approach, enabled by the E. lineata transcriptome assembly, I estimated the divergence date for these two anemones between 215-364 million years ago, thereby establishing an upper bound for the innovation of E. lineata's derived, parasitic life history. Testing a hypothesis that Wnt signaling, which patterns the oral-aboral (OA) axis during embryogenesis, also patterns the OA axis during regeneration, I demonstrated that canonical Wnt signaling is sufficient for oral tissue fate across alternate life histories (embryogenesis and regeneration) of N. vectensis. Taken together, these dissertation research activities constitute an integrative approach to investigating the evolution of life histories, and are a step towards establishing E. lineata and N. vectensis as models for studying the evolutionary developmental mechanisms of parasitism and regeneration

    BioSilicoSystems - A Multipronged Approach Towards Analysis and Representation of Biological Data (PhD Thesis)

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    The rising field of integrative bioinformatics provides the vital methods to integrate, manage and also to analyze the diverse data and allows gaining new and deeper insights and a clear understanding of the intricate biological systems. The difficulty is not only to facilitate the study of heterogeneous data within the biological context, but it also more fundamental, how to represent and make the available knowledge accessible. Moreover, adding valuable information and functions that persuade the user to discover the interesting relations hidden within the data is, in itself, a great challenge. Also, the cumulative information can provide greater biological insight than is possible with individual information sources. Furthermore, the rapidly growing number of databases and data types poses the challenge of integrating the heterogeneous data types, especially in biology. This rapid increase in the volume and number of data resources drive for providing polymorphic views of the same data and often overlap in multiple resources. 

In this thesis a multi-pronged approach is proposed that deals with various methods for the analysis and representation of the diverse biological data which are present in different data sources. This is an effort to explain and emphasize on different concepts which are developed for the analysis of molecular data and also to explain its biological significance. The hypotheses proposed are in context with various other results and findings published in the past. The approach demonstrated also explains different ways to integrate the molecular data from various sources along with the need for a comprehensive understanding and clear projection of the concept or the algorithm and its results, but with simple means and methods. The multifarious approach proposed in this work comprises of different tools or methods spanning significant areas of bioinformatics research such as data integration, data visualization, biological network construction / reconstruction and alignment of biological pathways. Each tool deals with a unique approach to utilize the molecular data for different areas of biological research and is built based on the kernel of the thesis. Furthermore these methods are combined with graphical representation that make things simple and comprehensible and also helps to understand with ease the underlying biological complexity. Moreover the human eye is often used to and it is more comfortable with the visual representation of the facts

    Genomic insights into ayurvedic and western approaches to personalized medicine

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    Ayurveda, an ancient Indian system of medicine documented and practised since 1500 B.C., follows a systems approach that has interesting parallels with contemporary personalized genomic medicine approaches to the understanding and management of health and disease. It is based on the trisutra, which are the three aspects of causes, features and therapeutics that are interconnected through a common organizing principle termed ‘tridosha’. Tridosha comprise three ascertainable physiological entities; vata (kinetic), pitta (metabolic) and kapha (potential) that are pervasive across systems, work in conjunction with each other, respond to the external environment and maintain homeostasis. Each individual is born with a specific proportion of tridosha that are not only genetically determined but also influenced by the environment during foetal development. Jointly they determine a person’s basic constitution, which is termed their ‘prakriti’. Development and progression of different diseases with their subtypes are thought to depend on the origin and mechanism of perturbation of the doshas, and the aim of therapeutic practice is to ensure that the doshas retain their homeostatic state. Similarly, western systems biology epitomized by translational P4 medicine envisages the integration of multiscalar genetic, cellular, physiological and environmental networks to predict phenotypic outcomes of perturbations. In this perspective article, we aim to outline the shape of a unifying scaffold that may allow the two intellectual traditions to enhance one another. Specifically, we illustrate how a unique integrative ‘Ayurgenomics’ approach can be used to integrate the trisutra concept of Ayurveda with genomics. We observe biochemical and molecular correlates of prakriti and show how these differ significantly in processes that are linked to intermediate patho-phenotypes, known to take different course in diseases. We also observe a significant enrichment of the highly connected hub genes which could explain differences in prakriti, focussing on EGLN1, a key oxygen sensor that differs between prakriti types and is linked to high altitude adaptation. Integrating our observation with the current literature, we demonstrate how EGLN1 could qualify as a molecular equivalent of tridosha that can modulate different phenotypic outcomes, where hypoxia is a cause or a consequence both during health and diseased states. Our studies affirm that integration of the trisutra framework through Ayurgenomics can guide the identification of predisposed groups of individuals and enable discovery of actionable therapeutic points in an individualized manner

    Role of network topology based methods in discovering novel gene-phenotype associations

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    The cell is governed by the complex interactions among various types of biomolecules. Coupled with environmental factors, variations in DNA can cause alterations in normal gene function and lead to a disease condition. Often, such disease phenotypes involve coordinated dysregulation of multiple genes that implicate inter-connected pathways. Towards a better understanding and characterization of mechanisms underlying human diseases, here, I present GUILD, a network-based disease-gene prioritization framework. GUILD associates genes with diseases using the global topology of the protein-protein interaction network and an initial set of genes known to be implicated in the disease. Furthermore, I investigate the mechanistic relationships between disease-genes and explain the robustness emerging from these relationships. I also introduce GUILDify, an online and user-friendly tool which prioritizes genes for their association to any user-provided phenotype. Finally, I describe current state-of-the-art systems-biology approaches where network modeling has helped extending our view on diseases such as cancer.La cèl•lula es regeix per interaccions complexes entre diferents tipus de biomolècules. Juntament amb factors ambientals, variacions en el DNA poden causar alteracions en la funció normal dels gens i provocar malalties. Sovint, aquests fenotips de malaltia involucren una desregulació coordinada de múltiples gens implicats en vies interconnectades. Per tal de comprendre i caracteritzar millor els mecanismes subjacents en malalties humanes, en aquesta tesis presento el programa GUILD, una plataforma que prioritza gens relacionats amb una malaltia en concret fent us de la topologia de xarxe. A partir d’un conjunt conegut de gens implicats en una malaltia, GUILD associa altres gens amb la malaltia mitjancant la topologia global de la xarxa d’interaccions de proteïnes. A més a més, analitzo les relacions mecanístiques entre gens associats a malalties i explico la robustesa es desprèn d’aquesta anàlisi. També presento GUILDify, un servidor web de fácil ús per la priorització de gens i la seva associació a un determinat fenotip. Finalment, descric els mètodes més recents en què el model•latge de xarxes ha ajudat extendre el coneixement sobre malalties complexes, com per exemple a càncer

    The social brain : how social stimuli are translated into neuroendocrine signals

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    Tese de doutoramento, Biologia (Ecofisiologia), Universidade de Lisboa, Faculdade de Ciências, 2014Animals continuously fine-tune the expression of social behaviors according to daily fluctuations on their social environment. But how does the social environment influence brain and behavior and what are the underlying physiologic, molecular and genetic mechanisms? Behavioral flexibility depends on neural plasticity of circuits underlying social behavior, which is achieved by social regulation of brain gene expression. Different neurogenomic states emerge in response to different external stimuli and switches between states are orchestrated by signaling pathways interfacing the social environment and the genotype. The goal of this thesis is to understand how social environment influences brain genomic transcription: (1) during a complex social interaction in zebrafish and (2) after stimulation with context-specific social olfactory stimuli in the Mozambique tilapia. Zebrafish, Danio rerio, has long been used as a model organism in developmental biology and genetics. Despite of their limited behavioral repertoire, the available genetic tools make it a promising model for the study of social behavior. In contrast, the Mozambique tilapia, Oreochromis mossambicus, has a rich behavioral repertoire in which visual and chemical information are conveyed to conspecifics, although having limited brain anatomy information and less genetic tools available. Our research suggests that the outcome of a single social interaction in zebrafish has consequences for subsequent behavior and significant impact on their brain transcriptome. These responses to social interactions seem to involve cognitive appraisal of stimuli, since the objective structure of the event does not trigger a genomic response but rather the appraisal the individual makes of the event. In tilapia, different chemical social cues not only affect neural activity of the olfactory epithelium but also elicit specific patterns of gene activation in brain areas related to olfactory processing. This reinforces the idea of an extensive transcriptional plasticity of teleost genomes, especially in response to rapid changes in social environment.Fundação para a Ciência e a Tecnologia (FCT, SFRH/BD/40976/2007, Programa Operacional Ciência e Inovação 2010 - POCI 2010

    Visualizing time-related data in biology, a review

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    Time is of the essence, also in biology. Monitoring disease progression or timing developmental defects are key aspects in the process of drug discovery and therapy trial. Furthermore, before deciphering the course of evolution of these complex processes, we need an understanding of the basic dynamics of biological phenomena that are often strictly time-regulated (e.g. circadian rhythms). With the advances in technologies able to measure timing effects and dynamics of regulatory aspects, visualization and analysis tools try to keep up the pace with the new challenge. Beyond the classical timeline plots, notable attempts at more involved temporal interpretation have been made in the recent years, but awareness of the available resources is still limited within the scientific community. Here we review some of the advances in biological visualization of time-driven processes and look at how they allow analyzing data now and in the future

    Pigmentation Pathway Evolution after Whole-Genome Duplication in Fish

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    Whole-genome duplications (WGDs) have occurred repeatedly in the vertebrate lineage, but their evolutionary significance for phenotypic evolution remains elusive. Here, we have investigated the impact of the fish-specific genome duplication (FSGD) on the evolution of pigmentation pathways in teleost fishes. Pigmentation and color patterning are among the most diverse traits in teleosts, and their pigmentary system is the most complex of all vertebrate groups
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