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      • Regime shifts in ecology and evolution

        Boettiger, Carl University of California, Davis 2012 해외박사(DDOD)

        RANK : 2607

        The most pressing issues of our time are all characterized by sudden regime shifts: the collapse of marine fisheries or stock-markets, the overthrow of governments, shifts in global climate. Regime shifts, or sudden transitions in dynamical behavior of a system, underly many important phenomena in ecological and evolutionary problems. How do they arise? How can we identify when a shift has occurred? Can we forecast these shifts? Here I address each of these central questions in the context of a particular system. First, I show how stochasticity in eco-evolutionary dynamics can give rise two different domains, or regimes, governing the behavior of evolutionary trajectories (Boettiger et al. 2010). In the next chapter, I turn to the question of identifying evolutionary shifts from data using phylogenetic trees and morphological trait data of extant species (Boettiger et al. 2012). In the last chapter, I adapt the approach of the previous section which allowed me to quantify the information available in a given data set that could detect a shift into an approach for detecting regime shifts in ecological time series data before the occur (Boettiger & Hastings 2012).

      • Molecular Mechanisms of Precise and Robust Gene Regulation in Drosophila

        Boettiger, Alistair Nicol University of California, Berkeley 2011 해외박사(DDOD)

        RANK : 2591

        The ornate arrangement of diverse cells into specialized tissues, organs, and higher structures characteristic of multicellular organisms is all encoded from the same genome sequence. Despite their differences, morphologically distinct cells (e.g. muscle cells and neurons) must transcribe many of the same genes. Morphological indistinguishable cells must often transcribe distinct sets of genes (e.g. different odorant receptor cells). The ensemble of genes expressed in a given cell---and the relative frequency they are expressed at, give each cell its characteristic identity more so than the presence of individual genes. Therefore understanding the genetic control of development and differentiation is a question not so much of the understanding the gene sequences themselves, but the regulatory structure of the genome which determines how they are deployed. In order for development to unravel in such a manner that each embryo makes it through the process with all the correct parts in the correct positions at the end, this process must be exceedingly precise. Though often taken for granted, this precision becomes particular impressive if one considers the frequency with which mistakes are made in intelligently designed human built assembly processes. The developing animal must position components correctly on scales of microns (e.g. tissue boundaries) and nanometers (e.g. neuron-junctions), has no external direction of assembly, and requires thermal noise to position many of its components (including essentially all transcription factors---proteins which regulate read access to the genome). It is not sufficient for the process to be precise. It must also be robust to changes in the conditions in which it operates, such as different thermal environments, nutrient conditions, and chemical environments. This robustness enables a certain degree of plasticity, such that some components of the system can change and evolve new functions, without causing catastrophic failure of the rest of the system. In my thesis research I have tried to explore some of the molecular mechanisms of gene regulation which support the precise and robust expression of multicellular genomes. Rapid advances in post-genomic technologies have exposed a broad range of fundamental differences in the organization and regulation of multicellular genomes such as Drosophila. I have worked primarily on two phenomena, the use of promoter proximal pausing as a regulatory strategy, and the use of multiple apparently redundant regulatory sequences to drive expression of the same gene. Discovery of both of these phenomena emerged from analysis of whole genome polymerase and transcription factor binding data. Using quantitative high resolution in situ and semi-automated computational image processing I have studied the detailed differences in the transcriptional activation and transcription frequency of genes regulated by these mechanisms. Through this analysis I have shown a strong correlation through more rapid and synchronous gene expression and regulation through release of promoter proximal paused polymerase. Theoretical modeling demonstrates that such an effect can be expected from regulating release of stable downstream state in a general assembly process (such as construction of the RNA Pol II pre-initiation complex). Analysis of gene expression driven by multiple enhancers with overlapping activity compared to constructs with only a single active enhancer revealed that the process by which an enhancer binds its target transcription factors and activates expression is often limiting enough that having a second independent copy can produce detectable changes in the frequency of transcription. This reduction of natural variation in gene activation is especially important under stress conditions, such as thermal stress or reduced levels of some of the activating factors. Robustness to this sort of variation may be important both for adaptation within a species and the flexibility to allow modification of interacting pathways in the course of evolutionary modification. These investigations also revealed a corrective propensity whereby the simultaneous activity of multiple enhancers, responding to repressors as well as activators, can give rise to correctly restricted gene expression even when the elements taken in isolation drive some degree of ectopic expression. So far both of these mechanisms have only been reliably documented in multicellular systems, suggesting that the precision and robustness they confer may be an innovation of metazoans in response to increased levels of coordination required to keep many cells functioning in the tight cooperation of a multicellular organism. Doubtless this is but scratching the surface of the mechanisms which ensure such precision and control. However the rapid improvements to both genomic tools and imaging technology make it like to be a promising field for further exploration for years to come.

      • Cellular mechanisms of plasticity in a neural circuit for song learning

        Boettiger, Charlotte Ann University of California, San Francisco 2000 해외박사(DDOD)

        RANK : 2591

        This study details physiological changes in the lateral portion of the magnocellular nucleus of the anterior neostriatum (LMAN) principal neurons that occur during sensory learning, potentially contributing to increased song selectivity and/or decreased ability to memorize new song. Such changes can be grouped into three classes: intrinsic properties, synaptic properties, and long-term synaptic plasticity. We established an <italic>in vitro</italic> slice preparation of the zebra finch anterior forebrain to characterize the intrinsic properties and excitatory synaptic transmission of LMAN principal neurons. Cells from birds in the early sensory learning phase (∼20d of age) had immature passive membrane properties, well developed spiking behavior, and received excitatory input from two sources: thalamic afferents (DLM), and recurrent axon collaterals (LMAN<sub>R</sub>). Both inputs were glutamatergic; responses to LMAN<sub>R</sub> inputs exhibited a relatively larger NMDA receptor-mediated component, and responses to DLM inputs showed marked paired-pulse depression (PPD). Comparing the intrinsic and synaptic properties of LMAN principal neurons across age groups demonstrated that changes occur in both over the course of sensory learning. Intrinsic property changes included a shortening of membrane time constants, and a decline in spike adaptation with age. These results are consistent with the developmental increase in auditory selectivity, and the increasingly sustained nature of LMAN auditory responses. Synaptic changes included decreases in the PPD of DLM inputs, and in the duration of LMAN<sub> R</sub> responses. Such changes are expected to reduce non-specific amplification of thalamic input by the recurrent circuitry of LMAN, resulting in higher fidelity transmission of thalamic input, potentially increasing auditory selectivity. These synaptic changes could be delayed by sensory isolation, indicating that they occur as a result of sensory learning. DLM and LMAN<sub>R</sub> synapses differed in the long-term activity-dependent plasticity they expressed, but both exhibited developmental change in such phenomena. At 20d, LMAN<sub>R</sub> synapses express a Hebbian, NMDA receptor-dependent LTP, while DLM inputs express a heterosynaptic LTD. Both types of plasticity were restricted to the sensory critical period, consistent with a role in sensory learning. Furthermore, the properties of the observed plasticity are well suited to establish circuitry within LMAN that could represent a memory of the tutor song.

      • The challenges of creating a professional model of teaching: Case studies of four Colorado charter schools

        Boettiger, Brigitte University of Colorado at Boulder 2001 해외박사(DDOD)

        RANK : 2591

        One of the purposes of charter school policy is to enhance teacher professionalism, yet initial research on charter schools presents conflicting findings on the issue. One of the goals of Colorado's legislation is to provide teachers with “new professional opportunities” and “responsibility for the learning program at a school site” (Senate Bill 93-183, p.2). Yet, there are many inherent contradictions in Colorado's legislation concerning the roles and responsibilities of teachers and little is known about how the policy is playing out. This research project investigates the issue through a comparative case study of four Colorado charter schools. Using qualitative methods, such as document analysis, focused observations, and semi-structured interviews with teachers, parents, and administrators, this study identifies the kinds of professional opportunities available to teachers in charter schools and determines whether a school is more bureaucratic or professional in its model of teaching. Different organizational arrangements, such as group initiating, governance structure, and curricular focus, are analyzed for how they influence the professional control of teachers at the four charter schools. Lastly, specific attributes of a professional model of teaching are also analyzed for their influence on one another. Some of these attributes include decision making, teacher collaboration and talk, opportunities for leadership, and workplace environment. Findings indicate that some Colorado charter schools do provide teachers with a variety of professional opportunities and more closely approximate a professional model of teaching. At these charter schools teachers have extensive professional control and decision making authority and regularly scheduled times for teacher collaboration. They can focus their talk on issues related to student learning and view their workplace as a respectful and supportive place. However, not all charter schools exhibit these characteristics to the same extent. There is a complex interplay between who was involved in developing a charter school, whether or not there are multiple teachers on a school's governing board, opportunities for teacher collaboration, and the flexibility of a school's governance structure. These variables influence the level of professional control afforded teachers, which, in turn, affects how well teachers can take responsibility for the learning program at a school site.

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