Scholarly Works, Fralin Life Sciences Institute
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Browsing Scholarly Works, Fralin Life Sciences Institute by Content Type "Article"
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- Anterograde or Retrograde Transsynaptic Circuit Tracing in Vertebrates with Vesicular Stomatitis Virus VectorsPan, Y. Albert; Beier, Kevin T.; Mundell, Nathan A.; Cepko, Constance L. (Wiley, 2016-01)Viruses have been used as transsynaptic tracers, allowing one to map the inputs and outputs of neuronal populations, due to their ability to replicate in neurons and transmit in vivo only across synaptically connected cells. To date, their use has been largely restricted to mammals. In order to explore the use of such viruses in an expanded host range, we tested the transsynaptic tracing ability of recombinant vesicular stomatitis virus (rVSV) vectors in a variety of organisms. Successful infection and gene expression were achieved in a wide range of organisms, including vertebrate and invertebrate model organisms. Moreover, rVSV enabled transsynaptic tracing of neural circuitry in predictable directions dictated by the viral envelope glycoprotein (G), derived from either VSV or rabies virus (RABV). Anterograde and retrograde labeling, from initial infection and/or viral replication and transmission, was observed in Old and NewWorld monkeys, seahorses, jellyfish, zebrafish, chickens, and mice. These vectors are widely applicable for gene delivery, afferent tract tracing, and/or directional connectivity mapping. Here, we detail the use of these vectors and provide protocols for propagating virus, changing the surface glycoprotein, and infecting multiple organisms using several injection strategies.
- Can Administrative Housing Data Replace Survey Data?Molfino, Emily; Korkmaz, Gizem; Keller, Sallie A.; Schroeder, Aaron; Shipp, Stephanie; Weinberg, Daniel H. (HUD, 2017)This article examines the feasibility of using local administrative data sources for enhancing and supplementing federally collected survey data to describe housing in Arlington County, Virginia. Using real estate assessment data and the American Community Survey (ACS) from 2009 to 2013, we compare housing estimates for six characteristics: number of housing units, type of housing unit, year built, number of bedrooms, housing value, and real estate taxes paid. The findings show that housing administrative data can be repurposed to enhance and supplement the ACS, but limitations exist. We then discuss the challenges of repurposing housing administrative data for research.
- Editorial: Signaling Proteins for Endosomal and Lysosomal FunctionCapelluto, Daniel G. S.; Conde, Cecilia B.; Tumbarello, David A.; van den Bogaart, Geert (Frontiers, 2021-12-16)
- An Ensemble Approach to Predicting the Impact of Vaccination on Rotavirus Disease in NigerPark, J.; Goldstein, J.; Haran, M.; Ferrari, M. (2017-05-09)Recently developed vaccines provide a new way of controlling rotavirus in sub-Saharan Africa. Models for the transmission dynamics of rotavirus are critical both for estimating current burden from imperfect surveillance and for assessing potential effects of vaccine intervention strategies. We examine rotavirus infection in the Maradi area in southern Niger using hospital surveillance data provided by Epicentre collected over two years. Additionally, a cluster survey of households in the region allows us to estimate the proportion of children with diarrhea who consulted at a health structure. Model fit and future projections are necessarily particular to a given model; thus, where there are competing models for the underlying epidemiology an ensemble approach can account for that uncertainty. We compare our results across several variants of Susceptible-Infectious-Recovered (SIR) compartmental models to quantify the impact of modeling assumptions on our estimates. Model-specific parameters are estimated by Bayesian inference using Markov chain Monte Carlo. We then use Bayesian model averaging to generate ensemble estimates of the current dynamics, including estimates of $R_0$, the burden of infection in the region, as well as the impact of vaccination on both the short-term dynamics and the long-term reduction of rotavirus incidence under varying levels of coverage. The ensemble of models predicts that the current burden of severe rotavirus disease is 2.9 to 4.1% of the population each year and that a 2-dose vaccine schedule achieving 70% coverage could reduce burden by 37-43%.
- A Genetic System for Methanocaldococcus jannaschii: An Evolutionary Deeply Rooted Hyperthermophilic MethanarchaeonSusanti, Dwi; Frazier, Mary C.; Mukhopadhyay, Biswarup (Frontiers, 2019-07-03)Phylogenetically deeply rooted methanogens belonging to the genus of Methanocaldococcus living in deep-sea hydrothermal vents derive energy exclusively from hydrogenotrophic methanogenesis, one of the oldest respiratory metabolisms on Earth. These hyperthermophilic, autotrophic archaea synthesize their biomolecules from inorganic substrates and perform high temperature biocatalysis producing methane, a valuable fuel and potent greenhouse gas. The information processing and stress response systems of archaea are highly homologous to those of the eukaryotes. For this broad relevance, Methanocaldococcus jannaschii, the first hyperthermophilic chemolithotrophic organism that was isolated from a deep-sea hydrothermal vent, was also the first archaeon and third organism for which the whole genome sequence was determined. The research that followed uncovered numerous novel information in multiple fields, including those described above. M. jannaschii was found to carry ancient redox control systems, precursors of dissimilatory sulfate reduction enzymes, and a eukaryotic-like protein translocation system. It provided a platform for structural genomics and tools for incorporating unnatural amino acids into proteins. However, the assignments of in vivo relevance to these findings or interrogations of unknown aspects of M. jannaschii through genetic manipulations remained out of reach, as the organism was genetically intractable. This report presents tools and methods that remove this block. It is now possible to knockout or modify a gene in M. jannaschii and genetically fuse a gene with an affinity tag sequence, thereby allowing facile isolation of a protein with M. jannaschii-specific attributes. These tools have helped to genetically validate the role of a novel coenzyme F420-dependent sulfite reductase in conferring resistance to sulfite in M. jannaschii and to demonstrate that the organism possesses a deazaflavin-dependent system for neutralizing oxygen.
- Modeling Commodity Flow in the Context of Invasive Species Spread: Study of Tuta absoluta in NepalSridhar, Venkataramana; Wu, S.; Shi, B.; Marathe, Achla; Sah, L.P.; Giri, A.P.; Colavito, L.A.; Nitin, K.S.; Asokan, R.; Muniappan, Rangaswamy (Muni); Norton, George W.; Adiga, A.; Eubank, Stephen (Virginia Tech, 2017)Trade and transport of goods is widely accepted as a primary pathway for the introduction and dispersal of invasive species. However, understanding commodity flows remains a challenge owing to its complex nature, unavailability of quality data and lack of systematic modeling methods. A robust network-based approach is proposed to model seasonal flow of agricultural produce and examine its role in pest spread. It is applied to study the spread of Tuta absoluta, a devastating pest of tomato in Nepal. Further, the long-term establishment potential of the pest and its economic impact on the country are assessed. Preliminary analyses indicate that T. absoluta will invade most major tomato production regions within a year of introduction and the economic impact of invasion could range from $17-25 million. The proposed approach is generic and particularly suited for data-poor scenarios.
- PLoS Computational Biology Conference Postcards from PSB 2010Datta, R. S.; Lux, Matthew W.; Bourne, Philip E. (Public Library of Science, 2010-04-29)Welcome to PLoS Conference Postcards. Postcards, as the name suggests, are designed to vividly recount to those not at a conference what happened at the event that was scientifically noteworthy and therefore make the reader wish they had attended. Postcards aim to be a departure from routine conference reports since they are written through the young and enthusiastic eyes of graduate students and postdoctoral fellows who intentionally focus on a small subset of what transpires at the meeting—from keynotes to research paper presentations to posters to working group discussions
- Robo2 determines subtype-specific axonal projections of trigeminal sensory neuronsPan, Y. Albert; Choy, Margaret; Prober, David A.; Schier, Aexander F. (Company of Biologists, 2012)How neurons connect to form functional circuits is central to the understanding of the development and function of the nervous system. In the somatosensory system, perception of sensory stimuli to the head requires specific connections between trigeminal sensory neurons and their many target areas in the central nervous system. Different trigeminal subtypes have specialized functions and downstream circuits, but it has remained unclear how subtype-specific axonal projection patterns are formed. Using zebrafish as a model system, we followed the development of two trigeminal sensory neuron subtypes: one that expresses trpa1b, a nociceptive channel important for sensing environmental chemicals; and a distinct subtype labeled by an islet1 reporter (Isl1SS). We found that Trpa1b and Isl1SS neurons have overall similar axon trajectories but different branching morphologies and distributions of presynaptic sites. Compared with Trpa1b neurons, Isl1SS neurons display reduced branch growth and synaptogenesis at the hindbrain-spinal cord junction. The subtype-specific morphogenesis of Isl1SS neurons depends on the guidance receptor Robo2. robo2 is preferentially expressed in the Isl1SS subset and inhibits branch growth and synaptogenesis. In the absence of Robo2, Isl1SS afferents acquire many of the characteristics of Trpa1b afferents. These results reveal that subtypespecific activity of Robo2 regulates subcircuit morphogenesis in the trigeminal sensory system.
- A syntactic model to design and verify synthetic genetic constructs derived from standard biological partsCai, Y.; Hartnett, B.; Gustafsson, C.; Peccoud, Jean (2007)Motivation: The sequence of artificial genetic constructs is composed of multiple functional fragments, or genetic parts, involved in different molecular steps of gene expression mechanisms. Biologists have deciphered structural rules that the design of genetic constructs needs to follow in order to ensure a successful completion of the gene expression process, but these rules have not been formalized, making it challenging for non-specialists to benefit from the recent progress in gene synthesis. Results: We show that context-free grammars (CFG) can formalize these design principles. This approach provides a path to organizing libraries of genetic parts according to their biological functions, which correspond to the syntactic categories of the CFG. It also provides a framework for the systematic design of new genetic constructs consistent with the design principles expressed in the CFG. Using parsing algorithms, this syntactic model enables the verification of existing constructs. We illustrate these possibilities by describing a CFG that generates the most common architectures of genetic constructs in Escherichia coli. Availability: A web site allows readers to experiment with the algorithms presented in this article: www.genocad.org
- Zebrabow: multispectral cell labeling for cell tracing and lineage analysis in zebrafish2013Pan, Y. Albert; Freundlich, Tom; Weissman, Tamily A.; Schoppik, David; Wang, X. Cindy; Zimmerman, Steve; Ciruna, Brian; Sanes, Joshua R.; Lichtman, Jeff W.; Schier, Aexander F. (Company of Biologists, 2013-07-01)Advances in imaging and cell-labeling techniques have greatly enhanced our understanding of developmental and neurobiological processes. Among vertebrates, zebrafish is uniquely suited for in vivo imaging owing to its small size and optical translucency. However, distinguishing and following cells over extended time periods remains difficult. Previous studies have demonstrated that Cre recombinase-mediated recombination can lead to combinatorial expression of spectrally distinct fluorescent proteins (RFP, YFP and CFP) in neighboring cells, creating a ‘Brainbow’ of colors. The random combination of fluorescent proteins provides a way to distinguish adjacent cells, visualize cellular interactions and perform lineage analyses. Here, we describe Zebrabow (Zebrafish Brainbow) tools for in vivo multicolor imaging in zebrafish. First, we show that the broadly expressed ubi:Zebrabow line provides diverse color profiles that can be optimized by modulating Cre activity. Second, we find that colors are inherited equally among daughter cells and remain stable throughout embryonic and larval stages. Third, we show that UAS:Zebrabow lines can be used in combination with Gal4 to generate broad or tissue-specific expression patterns and facilitate tracing of axonal processes. Fourth, we demonstrate that Zebrabow can be used for long-term lineage analysis. Using the cornea as a model system, we provide evidence that embryonic corneal epithelial clones are replaced by large, wedge-shaped clones formed by centripetal expansion of cells from the peripheral cornea. The Zebrabow tool set presented here provides a resource for next-generation color-based anatomical and lineage analyses in zebrafish.