Alumni Dissertations and Theses

 
 

Alumni Dissertations and Theses

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  • Multifunctional Roles of APL-1 in C. elegans

    Author:
    Collin Ewald
    Year of Dissertation:
    2011
    Program:
    Biology
    Advisor:
    Christine Li
    Abstract:

    Alzheimer's disease is an age-dependent disorder and the most common type of dementia. The most prevalent mutations associated with familial Alzheimer's Disease are found in the gene encoding the amyloid precursor protein (APP) or in the presenilin genes, which encode proteases that cleave APP. In mice, knockout of the APP gene family leads to lethality and type II lissencephaly, while overexpression of APP causes a shortening in lifespan and learning defects. However, the cellular function of APP and the pathways in which APP acts are unknown. Here we investigate the role of APL-1, the Caenorhabditis elegans orthologue of APP. Specifically, we expressed APL-1 with different promoters to determine the effect of APL-1 overexpression on several parameters: lifespan, development, and learning. Overexpression of APL-1 driven by its endogenous promoter accelerated aging and thereby shortened lifespan. By contrast, overexpression of APL-1 driven by the snb-1 promoter slowed aging and thereby prolonged lifespan. This extended lifespan was dependent on signals from the gonad and activity of the transcription factor DAF-16/FOXO and the nuclear hormone receptor DAF-12/NHR. Several other APL-1 overexpression phenotypes, including slowed developmental progression, were also dependent on daf-16/FOXO and daf-12/NHR activity. Lastly, pan-neuronal expression of APL-1 caused impairments in olfactory and gustatory avoidance behaviors as well as impairments in touch habituation. These defects were rescued by decreased activity of daf-16/FOXO and daf-12/NHR. Our results suggest that signaling of neuronally expressed APL-1 perturbs learning via the insulin/IGF-1 and the TGF-β pathways. Hence, APL-1 is a multifunctional protein that signals in multiple pathways to affect lifespan, development, and learning. In light of our results, we suggest that the shortened lifespan and learning defects in mice with APP overexpression might be mediated via the insulin/IGF-1 pathway. Interestingly, AD is strongly associated with type 2 diabetes and some AD patients show brain specific diabetes.

  • DIVERSITY, RESOURCE PARTITIONING, AND SPECIES TURNOVER IN NEOTROPICAL SAPROXYLIC BEETLES (COLEOPTERA: CERAMBYCIDAE, CURCULIONIDAE) ASSOCIATED WITH TREES IN THE BRAZIL NUT FAMILY (LECYTHIDACEAE)

    Author:
    Joyce Fassbender
    Year of Dissertation:
    2013
    Program:
    Biology
    Advisor:
    Amy Berkov
    Abstract:

    Deforestation and global changes in temperature and moisture associated with rising levels of greenhouse gases are expected to have strong, direct effects on abundance of wood-boring beetles through loss of larval feeding substrates, and indirect effects through climate and microclimate change. This dissertation examines Neotropical saproxylic beetle (Coleoptera: Curculionidae) diversity, niche breadth, and resource partitioning, and predicts possible impacts of climate change. Data from beetle rearing experiments conducted in French Guiana and Peru were analyzed to assess species richness, abundance, host specificity, seasonality and stratification of wood-boring beetles associated with the Brazil nut family (Lecythidaceae). Niche stability was assessed over time (French Guiana 1995-96, 2007-08) and space (Peru 2003-05). In French Guiana, resource partitioning was analyzed among the most abundant subfamilies of Curculionidae (Conoderinae, Scolytinae, Platypodinae) and Cerambycidae (Cerambycinae, Lamiinae). Species richness was higher in Peru than French Guiana, with high beta-diversity between sites; largely due to the prevalence of rare species in Peru. In both localities, most beetle species were disproportionately associated with the host Eschweilera coriacea (DC) S.A. Mori. In French Guiana, comparatively large cerambycids were more abundant during the dry season and seemed relatively drought tolerant. Small-bodied curculionids were most abundant during the rainy season, with weevils and platypodines best represented at ground stratum. In Peru, weevils were more abundant during the dry season. Cerambycinae, which are preferentially associated with the dry season canopy stratum, are expected to thrive should regional climates become warmer and drier. Lamiinae may respond by seasonally alternating stratum. Many Neotropical weevils and bark/ambrosia beetles seem strongly moisture-dependent, and populations are expected to be negatively impacted by increased drought. The Brazil nut family is threatened by both habitat fragmentation and climate change. The favored host species, E. coriacea, has a wide geographic distribution that extends into western Amazonia, which is not expected to experience severe precipitation changes, and could provide refuge for saproxylic beetles currently associated with Lecythidaceae. Saproxylic beetles, especially curculionids, may be less impacted by direct effects of host loss than indirect effects of climate change, especially northeast Amazonia which is expected to experience declining precipitation and longer dry seasons.

  • Evolution of Song Culture in the Zebra Finch

    Author:
    Olga Feher
    Year of Dissertation:
    2009
    Program:
    Biology
    Advisor:
    Ofer Tchernichovski
    Abstract:

    Cumulative cultural evolution is when behavior in subsequent generations of learners builds on the accumulated information of previous generations to such an extent that no individual learner can produce the behavior on its own. Many examples exist in humans, but in nonhuman animals there are only a handful of suspected cases. Here, we provide the first demonstration of cumulative cultural evolution in the laboratory in nonhuman animals. We raised zebra finches in complete acoustic and social isolation to create "uncultured" animals. Isolate zebra finches sing unstructured songs that are different from wild-type songs in many aspects such as spectral details of syllables and syntactic organization. We developed an automated procedure to quantify the differences between isolate and wild-type song at different timescales of song structure: spectral features, duration of sounds, and song rhythm. We then used the isolate birds to teach their songs to juveniles who became the tutors for the next generations of learners and so on recursively. We followed the evolution of isolate song over multiple generations. We found that isolate song was gradually transforming into wild-type song over 3-4 learning generations. In addition to this experiment where we trained young birds in individual tutor-pupil pairs, we established a semi-natural colony with an isolate founder and tracked song changes over multiple generations of learners. In the colony, the song also progressed towards wild-type song in a few generations, but some of the details of the changes differed between the two conditions. The rapid evolution indicates that wild-type song culture is encoded in every bird, but it takes multiple generations to surface. The young birds used imitation biases to change isolate song features into wild-type features.

  • C. elegans ADAMTS ADT-2 regulates body size and cuticle collagen organization

    Author:
    Thilini Fernando
    Year of Dissertation:
    2010
    Program:
    Biology
    Advisor:
    Cathy Savage-Dunn
    Abstract:

    The regulation of body size is a fundamental feature of animals critical to their survival and fitness, yet its underlying mechanisms remain poorly understood. In C. elegans, the DBL-1 signaling pathway plays a major role in growth control. The mechanisms by which other pathways regulate body size function, however, are less well understood. To identify additional genes involved in body size regulation, a genetic screen for small mutants was previously performed. One of the genes identified in that screen was sma 21. I now demonstrate that sma 21 encodes ADT-2, a member of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family of secreted metalloproteases. ADAMTS proteins are believed to remodel the extracellular matrix (ECM) and may modulate the activity of extracellular signals. Genetic interactions suggest that ADT-2 acts in parallel with known size regulatory pathways. I further demonstrate that ADT-2 activity is required for normal cuticle collagen fibril organization and adt-2 regulatory sequences drive expression in glial-like cells. ADT-2::GFP fusion protein is localized in the alae and the annuli of the cuticle. We therefore show that ADT-2 is secreted into the cuticle where it may act to proteolytically process secreted collagen or other ECM molecules required for normal cuticle structure and body size.

  • The effects of chronic habitat degradation on the physiology and metal accumulation of eastern oysters (Crassostrea virginica) in the Hudson Raritan Estuary

    Author:
    Allison Fitzgerald
    Year of Dissertation:
    2013
    Program:
    Biology
    Advisor:
    William Wallace
    Abstract:

    The Hudson Raritan Estuary (HRE) was once home an abundant population of the eastern oyster, Crassostrea virginica. Years of habitat degradation, via removal of habitat and shell substrate, overfishing of the population, and inputs of organic and inorganic contaminants, all led to the decline of this previous keystone species. The HRE today is a highly eutrophic environment, with increased sediment inputs, periods of low dissolved oxygen, algal blooms, and hotspots of contaminants throughout. The current study was designed to understand how a chronically degraded habitat, as is present in the HRE now, affects both juvenile and adult oyster physiology. There are three parts to this study: in the first, a large scale field transplant study was deployed to determine how juvenile oyster health and subcellular physiology are altered over a continuum of sites across the HRE, and if subcellular metal accumulation related to alterations in physiology. Using eight sites across the HRE, it was apparent that there are many site-specific factors that affect oyster physiology, and the synergistic effects of these abiotic and biotic factors together influence oyster physiology the most. There was no one factor that could be isolated as a key parameter to determine future oyster restoration. The second part used a field transplant study to examine the role of a degraded habitat on adult oysters and reproduction. Using Vitellogenin protein and energy expenditures to estimate oyster reproduction, it was seen that adult oysters respond much slower than juveniles and no differences were seen between highly degraded habitats and less degraded habitats. Thirdly, both juveniles and adults were observed to accumulate non-essential metals (Cd and Hg) in the field. In order to determine if metal accumulation is the sole cause of physiological alterations, a laboratory exposure was designed to determine if changes in subcellular physiology could be correlated specifically to subcellular accumulation of Cd or Hg, when no other abiotic factors are able to influence oyster health. It was observed that Cd accumulation lead to physiological changes, but Hg accumulation did not. Using this information about the site-specific nature of oyster physiology and how metal accumulation can alter physiology will allow researchers to choose future restoration sites and set up projects that will allow for maximum growth and survival.

  • EVOLUTION, PHYLOGEOGRAPHY AND SPECIES BOUNDARIES OF THE RINGNECK SNAKE GENUS DIADOPHIS

    Author:
    Frank Fontanella
    Year of Dissertation:
    2009
    Program:
    Biology
    Advisor:
    Mark Siddall
    Abstract:

    EVOLUTION, PHYLOGEOGRAPHY AND SPECIES BOUNDARIES OF THE RINGNECK SNAKE GENUS DIADOPHIS ADVISER: Dr. Mark E. Siddall The monotypic snake genus Diadophis Baird and Girard, 1853 is one of the most widely distributed and morphologically variable snakes throughout North America. This snake (Diadophis punctatus) exploits a variety of habitats and ecological niches ranging from the mixed hardwood forests of southern Canada to the desert of the Southwestern US and Central Mexico (excluding the northern Great Plains states. Ringneck snakes have traditionally been divided into 13 subspecies based on a combination of morphology and geography. This study has provided the first range-wide molecular study and provides a framework for the origin, evolution and biodiversity in the genus Diadophis. Analysis of mtDNA sequence data inferred 16 mtDNA lineages that replace each other geographically across the United States and into central Mexico. In contrast to previous hypothesis, ancestral area reconstructions inferred an origin for D. punctatus in the southeastern United States during the Miocene, followed by a southeast to northeast then westward directionality of historical migration. Demographic analyses indicate that independent lineages currently occupying previously glaciated or unsuitable areas in eastern, central and western U.S. underwent post-glacial population expansion likely from southern refugia during the late Pleistocene/early Holocene. Conversely, southern lineages display patterns consistent with long-term population stability. For the purposes of species delineation, ecological niche modeling does not show isolation due to unsuitable habitat. Ten novel microsatellite loci developed for this study suggest that most species boundaries are maintained through a balance of selection and dispersal in hybrid zones. Based on the geographic distribution of the mtDNA lineages and the microsatellite frequency data, we hypothesize that there are eight species within the genus Diadophis throughout the Eastern United States. This body of work provides a rich framework for further study including, examining species boundaries in the western lineages, determining population structure within species, and detailed examination of hybrid zones.

  • Phylogenetics, biogeography and co-adaptation between a Batesian model (Micrurus fulvius) and mimic (Lampropeltis triangulum)

    Author:
    Michael Friedman
    Year of Dissertation:
    2009
    Program:
    Biology
    Advisor:
    Rob DeSalle
    Abstract:

    The coral snake, Micrurus fulvius (Elapidae), and the scarlet king snake, Lampropeltis triangulum (Colubridae), members of a Batesian mimicry complex in the southeastern and southern United States were subjects of a study of model-mimic co-evolution. Inferring co-evolution required discovery of distinct terminals within each group, for posterior phylogenetic inference and analysis of co-variation of color patterns among sympatric populations of each species. In addition, haplotype and population differentiation were assessed. Also, hypotheses regarding selection on color patterns were tested. The latter included model-mimic tracking, environmental effects and frequency dependence of mimetic color pattern variation. Population Aggregation Analysis failed to diagnose terminals for either group. Haplotype and population genetic analyses showed both groups to be largely panmictic, with some north/south differentiation. Morphometric analyses of means and variations in proportions of color pattern components failed to reveal geographic tracking by mimics of models, but manifested possible independent geographic or environmental effects on each of the species. Frequency-dependent selection was falsified for color pattern variation in mimics.

  • Islet-brain-2: a novel postsynaptic density protein linked to an autism spectrum disorder

    Author:
    Joanna Giza
    Year of Dissertation:
    2010
    Program:
    Biology
    Advisor:
    Mitchell Goldfarb
    Abstract:

    Islet-brain-2 (IB2) is a neuronal protein, whose functions are not well understood. Based upon its sequence homology to JNK-interacting protein 1 (JIP1) and biochemical studies, IB2 has been described as a putative scaffold for mitogen activated protein kinase (MAPK) signaling. IB2 has been documented to interact with a wide array of functionally unrelated proteins, which has complicated efforts to confirm its biochemical role in vivo. In order to investigate the IB2 function in the nervous system, we have generated Ib2 null mice. The mutants are viable and their expression of genes neighboring Ib2 is unaffected. Ib2 knockout mice display developmental delay in grip strength until 5 weeks (P35) of age. Their behavioral analysis following disappearance of this defect shows significant deficits in their motor learning abilities. In addition, mutant mice exhibit marked reduction in social interactions, delayed fear induced learning and unresponsiveness to the environment in various behavioral tasks. These complex atypical behaviors are reminiscent of autism spectrum disorders (ASDs). Interestingly, the human Ib2 gene resides within the deleted chr22qter region in Phelan-McDermid syndrome and patients with this disorder manifest similar deficits as observed in our Ib2 null mice, suggesting that Ib2 loss-of-function is a promising candidate model for this disorder. Recent developments in the ASDs field implicate as a major culprit defective synaptic function. Using brain fractionation and co-immunoprecipitation methods, we show that IB2 is an integral component of the postsynaptic density (PSD). Immunofluorescence shows IB2 concentrated within dendritic spine heads. Ib2 mutation did not alter expression levels of many other common PSD components such as PSD95 and AMPA-type and NMDA-type receptors subunits. Signaling analyses conducted in Ib2 null cultured cortical neurons failed to reveal deficits in NMDA-evoked signaling through known IB2-interacting partners TIAM1 and p38MAPK, suggesting that IB2 modulates synaptic and behavioral functions through as yet unknown molecular mechanisms.

  • MAG and myelin block the ability of BDNF to overcome inhibition of axonal regeneration by inhibiting BDNF's activation of Rap1

    Author:
    Vasiliki Gkioka
    Year of Dissertation:
    2009
    Program:
    Biology
    Advisor:
    Marie Filbin
    Abstract:

    It is well established that axons of the adult mammalian CNS do not regenerate if injured by trauma, or if afflicted by various neurodegenerative conditions. It is also well established that myelin, the insulating and protective membranous sheath around neurons, contains several proteins that act as inhibitors of neurite outgrowth, such as MAG, and damaged myelin is one of the factors limiting CNS regeneration after injury. Because of their well established role in neuronal development, survival, and function, neurotrophins have been candidates for therapeutic intervention in the nervous system for many years, and have already been used in clinical trials for various neurological conditions. We have previously shown that neurotrophins elevate cAMP. If the cAMP signaling cascade is initiated in neurons exposed to MAG and myelin, with the non-hydrolyzable analogue dibutyryl-cAMP, inhibition of neurite outgrowth by both is blocked in vitro. Importantly, we have shown that if cAMP is elevated in damaged neurons, nerve regeneration is promoted in vivo. We have also observed that neurotrophin-induced cAMP elevation is blocked in the presence of MAG, and neurotrophins are effective in overcoming MAG inhibition only by overnight pre-exposure of neurons to them, a procedure we call "priming with neurotrophins". Therefore, understanding the mechanism of MAG and myelin's block of neurotrophin signaling could result in the design of therapeutics that target only specific molecules in the neurotrophin cascade, in order to potentiate only specific and desirable effects of neurotrophins, for specific types of injury or disease. We have found that MAG and myelin block the BDNF activation of Rap1, one of the Ras-superfamily members activated in the neurotrophin cascade, which is also part of the cAMP signaling network, due to cAMP-activation of one of its upstream activators, EPAC. We have also shown that MAG and myelin treatment of neurons results in upregulation of the protein levels of the Rap1 inactivator Rap1GAP, which provides a mechanism for the block of Rap1 activation by BDNF. Additionally we have shown that priming of neurons with the EPAC-specific cAMP analogue 8-CPT-2Me-cAMP, like priming with neurotrophins, is sufficient to overcome inhibition by MAG. Moreover, infection of neurons with adenoviruses carrying wild type Rap1, or the RapGAP insensitive mutant Rap1F64A, improved growth on MAG and myelin. Infection of neurons with adenovirus carrying the Rap1 inactivator Rap1GAPI blocked the ability of neurons to extend neurites, demonstrating an essential role of the Rap1 family in regulating neurite outgrowth. Besides its implications for therapeutic intervention after CNS trauma, the modulation of the neurotrophin cascade by MAG demonstrated here might be a new manifestation of the role of MAG and myelin in restricting plasticity in the intact CNS.

  • Systematics of the North American Scorpion Subfamily Syntropinae ( Scorpiones: Vaejovidae)

    Author:
    Edmundo Gonzalez
    Year of Dissertation:
    2013
    Program:
    Biology
    Advisor:
    Lorenzo Prendini
    Abstract:

    The first phylogenetic analysis and a taxonomic revision of the North American vaejovid scorpion subfamily Syntropinae Kraepelin, 1905 are presented. The phylogeny is based on a simultaneous analysis of molecules (5 loci) and morphological characters (continuous and discrete). The current classification of the subfamily (Soleglad and Fet, 2008) was tested for monophyly and the relative positions of insertae sedis taxa putatively related to the subfamily were investigated. Nodal stability and nodal support for the resultant topologies were high; although the molecules and morphology had dissimilar phylogenetic signals simultaneous analyses enhanced the overall signal and thus generated the hypothesis with the most explanatory power. Syntropinae and Stahnkeini Soleglad and Fet, 2008 were recovered as monophyletic. The Syntropinae comprised six monophyletic groups that contradicted the current classification. The following taxonomic emendations are proposed. The tribe Paravaejovini Soleglad and Fet, 2008 and the subtribe Thorellina Soleglad and Fet, 2008 are synonymized with Syntropinae; the Syntropinae is redefined with eleven genera. Six new genera are described, Balsateres n. gen., Chihuahuanus, n. gen., Konetontli, n. gen., Maaykuyak, n. gen., Mesomexovis, n. gen., and Vizcaino, n. gen. Hoffmannius, syn. n. is synonymized with Paravaejovis and 15 species are transferred to other genera. Five subspecies are elevated to species, two restored from synonymy and 26 new species are described. Possible scenarios of the evolution and distributional pattern of the genera and species are presented, from a historical and ecological perspective.