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Articles 91 - 120 of 212

Full-Text Articles in Genetics and Genomics

Key Genes For Modulating Information Flow Play A Temporal Role As Breast Tumor Coexpression Networks Are Dynamically Rewired By Letrozole, Nadia M. Penrod, Jason H. Moore May 2013

Key Genes For Modulating Information Flow Play A Temporal Role As Breast Tumor Coexpression Networks Are Dynamically Rewired By Letrozole, Nadia M. Penrod, Jason H. Moore

Dartmouth Scholarship

Genes do not act in isolation but instead as part of complex regulatory networks. To understand how breast tumors adapt to the presence of the drug letrozole, at the molecular level, it is necessary to consider how the expression levels of genes in these networks change relative to one another. Using transcriptomic data generated from sequential tumor biopsy samples, taken at diagnosis, following 10-14 days and following 90 days of letrozole treatment, and a pairwise partial orrelation statistic, we build temporal gene coexpression networks. We characterize the structure of each network and identify genes that hold prominent positions for maintaining …


High Sine Rna Expression Correlates With Post-Transcriptional Downregulation Of Brca1, Maureen Peterson, Vicki Chandler, Giovanni Bosco Apr 2013

High Sine Rna Expression Correlates With Post-Transcriptional Downregulation Of Brca1, Maureen Peterson, Vicki Chandler, Giovanni Bosco

Dartmouth Scholarship

Short Interspersed Nuclear Elements (SINEs) are non-autonomous retrotransposons that comprise a large fraction of the human genome. SINEs are demethylated in human disease, but whether SINEs become transcriptionally induced and how the resulting transcripts may affect the expression of protein coding genes is unknown. Here, we show that downregulation of the mRNA of the tumor suppressor gene BRCA1 is associated with increased transcription of SINEs and production of sense and antisense SINE small RNAs. We find that BRCA1 mRNA is post-transcriptionally down-regulated in a Dicer and Drosha dependent manner and that expression of a SINE inverted repeat with sequence identity …


Functional Annotation And Comparative Analysis Of A Zygopteran Transcriptome, Alexander G. Shanku, Mark A. Mcpeek, Andrew D. Kern Apr 2013

Functional Annotation And Comparative Analysis Of A Zygopteran Transcriptome, Alexander G. Shanku, Mark A. Mcpeek, Andrew D. Kern

Dartmouth Scholarship

In this paper we present a de novo assembly of the transcriptome of the damselfly (Enallagma hageni) through the use of 454 pyrosequencing. E. hageni is a member of the suborder Zygoptera, in the order Odonata, and Odonata organisms form the basal lineage of the winged insects (Pterygota). To date, sequence data used in phylogenetic analysis of Enallagma species have been derived from either mitochondrial DNA or ribosomal nuclear DNA. This Enallagma transcriptome contained 31,661 contigs that were assembled and translated into 14,813 individual open reading frames. Using these data, we constructed an extensive dataset of 634 orthologous nuclear protein-encoding …


Functional Analysis Of The Aspergillus Nidulans Kinome, Colin P. De Souza, Shahr B. Hashmi, Aysha H. Osmani, Peter Andrews, Carol S. Ringelberg, Jay C. Dunlap, Stephen A. Osmani Mar 2013

Functional Analysis Of The Aspergillus Nidulans Kinome, Colin P. De Souza, Shahr B. Hashmi, Aysha H. Osmani, Peter Andrews, Carol S. Ringelberg, Jay C. Dunlap, Stephen A. Osmani

Dartmouth Scholarship

The filamentous fungi are an ecologically important group of organisms which also have important industrial applications but devastating effects as pathogens and agents of food spoilage. Protein kinases have been implicated in the regulation of virtually all biological processes but how they regulate filamentous fungal specific processes is not understood. The filamentous fungus Aspergillus nidulans has long been utilized as a powerful molecular genetic system and recent technical advances have made systematic approaches to study large gene sets possible. To enhance A. nidulans functional genomics we have created gene deletion constructs for 9851 genes representing 93.3% of the encoding genome. …


Atypical Glycolysis In Clostridium Thermocellum, Jilai Zhou, Daniel G. Olson, D. Aaron Argyros, Yu Deng, Walter M. Van Gulik, Johannes P. Van Dijken, Lee R. Lynd Feb 2013

Atypical Glycolysis In Clostridium Thermocellum, Jilai Zhou, Daniel G. Olson, D. Aaron Argyros, Yu Deng, Walter M. Van Gulik, Johannes P. Van Dijken, Lee R. Lynd

Dartmouth Scholarship

Cofactor specificities of glycolytic enzymes in Clostridium thermocellum were studied with cellobiose-grown cells from batch cultures. Intracellular glucose was phosphorylated by glucokinase using GTP rather than ATP. Although phosphofructokinase typically uses ATP as a phosphoryl donor, we found only pyrophosphate (PPi)-linked activity. Phosphoglycerate kinase used both GDP and ADP as phosphoryl acceptors. In agreement with the absence of a pyruvate kinase sequence in the C. thermocellum genome, no activity of this enzyme could be detected. Also, the annotated pyruvate phosphate dikinase (ppdk) is not crucial for the generation of pyruvate from phosphoenolpyruvate (PEP), as deletion of the ppdk gene did …


Identification Of Snps Associated With Variola Virus Virulence, Anne Gatewood Hoen, Shea N. Gardner, Jason H. Moore Feb 2013

Identification Of Snps Associated With Variola Virus Virulence, Anne Gatewood Hoen, Shea N. Gardner, Jason H. Moore

Dartmouth Scholarship

Background: Decades after the eradication of smallpox, its etiological agent, variola virus (VARV), remains a threat as a potential bioweapon. Outbreaks of smallpox around the time of the global eradication effort exhibited variable case fatality rates (CFRs), likely attributable in part to complex viral genetic determinants of smallpox virulence. We aimed to identify genome-wide single nucleotide polymorphisms associated with CFR. We evaluated unadjusted and outbreak geographic location-adjusted models of single SNPs and two- and three-way interactions between SNPs. Findings: Using the data mining approach multifactor dimensionality reduction (MDR), we identified five VARV SNPs in models significantly associated with CFR. The …


How Long Is A Piece Of Loop?, Yoonjoo Choi, Sumeet Agarwal, Charlotte M. Deane Feb 2013

How Long Is A Piece Of Loop?, Yoonjoo Choi, Sumeet Agarwal, Charlotte M. Deane

Dartmouth Scholarship

Loops are irregular structures which connect two secondary structure elements in proteins. They often play important roles in function, including enzyme reactions and ligand binding. Despite their importance, their structure remains difficult to predict. Most protein loop structure prediction methods sample local loop segments and score them. In particular protein loop classifications and database search methods depend heavily on local properties of loops. Here we examine the distance between a loop's end points (span). We find that the distribution of loop span appears to be independent of the number of residues in the loop, in other words the separation between …


Candida Albicans Induces Arginine Biosynthetic Genes In Response To Host-Derived Reactive Oxygen Species, Claudia Jimenez-Lopez, John R. Collette, Kimberly M. Brothers, Kelly M. Shepardson, Robert A. Kramer Jan 2013

Candida Albicans Induces Arginine Biosynthetic Genes In Response To Host-Derived Reactive Oxygen Species, Claudia Jimenez-Lopez, John R. Collette, Kimberly M. Brothers, Kelly M. Shepardson, Robert A. Kramer

Dartmouth Scholarship

The interaction of Candida albicans with phagocytes of the host's innate immune system is highly dynamic, and its outcome directly impacts the progression of infection. While the switch to hyphal growth within the macrophage is the most obvious physiological response, much of the genetic response reflects nutrient starvation: translational repression and induction of alternative carbon metabolism. Changes in amino acid metabolism are not seen, with the striking exception of arginine biosynthesis, which is upregulated in its entirety during coculture with macrophages. Using single-cell reporters, we showed here that arginine biosynthetic genes are induced specifically in phagocytosed cells. This induction is …


Chapter 11: Genome-Wide Association Studies, William S. Bush, Jason H. Moore Dec 2012

Chapter 11: Genome-Wide Association Studies, William S. Bush, Jason H. Moore

Dartmouth Scholarship

Genome-wide association studies (GWAS) have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS.


Septin Phosphorylation And Coiled-Coil Domains Function In Cell And Septin Ring Morphology In The Filamentous Fungus Ashbya Gossypii, Rebecca A. Meseroll, Patricia Occhipinti, Amy S. Gladfelter Nov 2012

Septin Phosphorylation And Coiled-Coil Domains Function In Cell And Septin Ring Morphology In The Filamentous Fungus Ashbya Gossypii, Rebecca A. Meseroll, Patricia Occhipinti, Amy S. Gladfelter

Dartmouth Scholarship

Septins are a class of GTP-binding proteins conserved throughout many eukaryotes. Individual septin subunits associate with one another and assemble into heteromeric complexes that form filaments and higher-order structures in vivo. The mechanisms underlying the assembly and maintenance of higher-order structures in cells remain poorly understood. Septins in several organisms have been shown to be phosphorylated, although precisely how septin phosphorylation may be contributing to the formation of high-order septin structures is unknown. Four of the five septins expressed in the filamentous fungus, Ashbya gossypii, are phosphorylated, and we demonstrate here the diverse roles of these phosphorylation sites …


Gametes: A Fast, Direct Algorithm For Generating Pure, Strict, Epistatic Models With Random Architectures, Ryan J. Urbanowicz, Jeff Kiralis, Nicholas A. Sinnott-Armstrong, Tamra Heberling, Jonathan M. Fisher, Jason H. Moore Oct 2012

Gametes: A Fast, Direct Algorithm For Generating Pure, Strict, Epistatic Models With Random Architectures, Ryan J. Urbanowicz, Jeff Kiralis, Nicholas A. Sinnott-Armstrong, Tamra Heberling, Jonathan M. Fisher, Jason H. Moore

Dartmouth Scholarship

Background: Geneticists who look beyond single locus disease associations require additional strategies for the detection of complex multi-locus effects. Epistasis, a multi-locus masking effect, presents a particular challenge, and has been the target of bioinformatic development. Thorough evaluation of new algorithms calls for simulation studies in which known disease models are sought. To date, the best methods for generating simulated multi-locus epistatic models rely on genetic algorithms. However, such methods are computationally expensive, difficult to adapt to multiple objectives, and unlikely to yield models with a precise form of epistasis which we refer to as pure and strict. Purely and …


Characterization Of Xylan Utilization And Discovery Of A New Endoxylanase In Thermoanaerobacterium Saccharolyticum Through Targeted Gene Deletions, Kara K. Podkaminer, Adam M. Guss, Heather L. Trajano, David A. Hogsett, Lee R. Lynd Sep 2012

Characterization Of Xylan Utilization And Discovery Of A New Endoxylanase In Thermoanaerobacterium Saccharolyticum Through Targeted Gene Deletions, Kara K. Podkaminer, Adam M. Guss, Heather L. Trajano, David A. Hogsett, Lee R. Lynd

Dartmouth Scholarship

The economical production of fuels and commodity chemicals from lignocellulose requires the utilization of both the cellulose and hemicellulose fractions. Xylanase enzymes allow greater utilization of hemicellulose while also increasing cellulose hydrolysis. Recent metabolic engineering efforts have resulted in a strain of Thermoanaerobacterium saccharolyticum that can convert C5 and C6 sugars, as well as insoluble xylan, into ethanol at high yield. To better understand the process of xylan solubilization in this organism, a series of targeted deletions were constructed in the homoethanologenic T. saccharolyticum strain M0355 to characterize xylan hydrolysis and xylose utilization in this organism. While the deletion of …


Insights Into Mrnp Biogenesis Provided By New Genetic Interactions Among Export And Transcription Factors, Francisco Estruch, Christine Hodge, Natalia Gómez-Navarro, Lorena Peiró-Chova, Catherine V. Heath, Charles N. Cole Sep 2012

Insights Into Mrnp Biogenesis Provided By New Genetic Interactions Among Export And Transcription Factors, Francisco Estruch, Christine Hodge, Natalia Gómez-Navarro, Lorena Peiró-Chova, Catherine V. Heath, Charles N. Cole

Dartmouth Scholarship

The various steps of mRNP biogenesis (transcription, processing and export) are interconnected. It has been shown that the transcription machinery plays a pivotal role in mRNP assembly, since several mRNA export factors are recruited during transcription and physically interact with components of the transcription machinery. Although the shuttling DEAD-box protein Dbp5p is concentrated on the cytoplasmic fibrils of the NPC, previous studies demonstrated that it interacts physically and genetically with factors involved in transcription initiation. We investigated the effect of mutations affecting various components of the transcription initiation apparatus on the phenotypes of mRNA export mutant strains. Our results show …


Farnesol And Cyclic Amp Signaling Effects On The Hypha-To-Yeast Transition In Candida Albicans, Allia K. Lindsay, Aurélie Deveau, Amy E. Piispanen, Deborah A. Hogan Aug 2012

Farnesol And Cyclic Amp Signaling Effects On The Hypha-To-Yeast Transition In Candida Albicans, Allia K. Lindsay, Aurélie Deveau, Amy E. Piispanen, Deborah A. Hogan

Dartmouth Scholarship

Candida albicans, a fungal pathogen of humans, regulates its morphology in response to many environmental cues and this morphological plasticity contributes to virulence. Farnesol, an autoregulatory molecule produced by C. albicans, inhibits the induction of hyphal growth by inhibiting adenylate cyclase (Cyr1). The role of farnesol and Cyr1 in controlling the maintenance of hyphal growth has been less clear. Here, we demonstrate that preformed hyphae transition to growth as yeast in response to farnesol and that strains with increased cyclic AMP (cAMP) signaling exhibit more resistance to farnesol. Exogenous farnesol did not induce the hypha-to-yeast transition in mutants …


Condensin Ii Promotes The Formation Of Chromosome Territories By Inducing Axial Compaction Of Polyploid Interphase Chromosomes, Christopher R. R. Bauer, Tom A. Hartl, Giovanni Bosco Aug 2012

Condensin Ii Promotes The Formation Of Chromosome Territories By Inducing Axial Compaction Of Polyploid Interphase Chromosomes, Christopher R. R. Bauer, Tom A. Hartl, Giovanni Bosco

Dartmouth Scholarship

The eukaryotic nucleus is both spatially and functionally partitioned. This organization contributes to the maintenance, expression, and transmission of genetic information. Though our ability to probe the physical structure of the genome within the nucleus has improved substantially in recent years, relatively little is known about the factors that regulate its organization or the mechanisms through which specific organizational states are achieved. Here, we show that Drosophila melanogaster Condensin II induces axial compaction of interphase chromosomes, globally disrupts interchromosomal interactions, and promotes the dispersal of peri-centric heterochromatin. These Condensin II activities compartmentalize the nucleus into discrete chromosome territories and indicate …


Gene Ontology Analysis Of Pairwise Genetic Associations In Two Genome-Wide Studies Of Sporadic Als, Nora Chung Kim, Peter C. Andrews, Folkert W. Asselbergs, H Robert Frost, Scott M. Williams, Brent T. Harris, Cynthia Read, Kathleen D. Askland, Jason H. Moore Jul 2012

Gene Ontology Analysis Of Pairwise Genetic Associations In Two Genome-Wide Studies Of Sporadic Als, Nora Chung Kim, Peter C. Andrews, Folkert W. Asselbergs, H Robert Frost, Scott M. Williams, Brent T. Harris, Cynthia Read, Kathleen D. Askland, Jason H. Moore

Dartmouth Scholarship

It is increasingly clear that common human diseases have a complex genetic architecture characterized by both additive and nonadditive genetic effects. The goal of the present study was to determine whether patterns of both additive and nonadditive genetic associations aggregate in specific functional groups as defined by the Gene Ontology (GO).


Two Boundaries Separate Borrelia Burgdorferi Populations In North America, Gabriele Margos, Jean I. Tsao, Santiago Castillo-Ramirez, Yvette A. Girard, Anne G. Hoen Jun 2012

Two Boundaries Separate Borrelia Burgdorferi Populations In North America, Gabriele Margos, Jean I. Tsao, Santiago Castillo-Ramirez, Yvette A. Girard, Anne G. Hoen

Dartmouth Scholarship

Understanding the spread of infectious diseases is crucial for implementing effective control measures. For this, it is important to obtain information on the contemporary population structure of a disease agent and to infer the evolutionary processes that may have shaped it. Here, we investigate on a continental scale the population structure of Borrelia burgdorferi, the causative agent of Lyme borreliosis (LB), a tick-borne disease, in North America. We test the hypothesis that the observed d population structure is congruent with recent population expansions and that these were preceded by bottlenecks mostly likely caused by the near extirpation in the 1900s …


Computational Design And Characterization Of A Temperature-Sensitive Plasmid Replicon For Gram Positive Thermophiles, Daniel G. Olson, Lee R. Lynd May 2012

Computational Design And Characterization Of A Temperature-Sensitive Plasmid Replicon For Gram Positive Thermophiles, Daniel G. Olson, Lee R. Lynd

Dartmouth Scholarship

Temperature-sensitive (Ts) plasmids are useful tools for genetic engineering, but there are currently none compatible with the gram positive, thermophilic, obligate anaerobe, Clostridium thermocellum. Traditional mutagenesis techniques yield Ts mutants at a low frequency, and therefore requires the development of high-throughput screening protocols, which are also not available for this organism. Recently there has been progress in the development of computer algorithms which can predict Ts mutations. Most plasmids currently used for genetic modification of C. thermocellum are based on the replicon of plasmid pNW33N, which replicates using the RepB replication protein. To address this problem, we set out …


Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit May 2012

Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit

Dartmouth Scholarship

There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.


The Tlo Proteins Are Stoichiometric Components Of Candida Albicans Mediator Anchored Via The Med3 Subunit, Anda Zhang, Kostadin O. Petrov, Emily R. Hyun, Zhongle Liu, Scott A. Gerber, Lawrence C. Myers May 2012

The Tlo Proteins Are Stoichiometric Components Of Candida Albicans Mediator Anchored Via The Med3 Subunit, Anda Zhang, Kostadin O. Petrov, Emily R. Hyun, Zhongle Liu, Scott A. Gerber, Lawrence C. Myers

Dartmouth Scholarship

The amplification of the TLO (for telomere-associated) genes in Candida albicans, compared to its less pathogenic, close relative Candida dubliniensis, suggests a role in virulence. Little, however, is known about the function of the Tlo proteins. We have purified the Mediator coactivator complex from C. albicans (caMediator) and found that Tlo proteins are a stoichiometric component of caMediator. Many members of the Tlo family are expressed, and each is a unique member of caMediator. Protein expression analysis of individual Tlo proteins, as well as the purification of tagged Tlo proteins, demonstrate that there is a large free population of Tlo …


Roles Of The Drosophila Sk Channel (Dsk) In Courtship Memory, Ahmad N. Abou Tayoun, Claudio Pikielny, Patrick J. Dolph Apr 2012

Roles Of The Drosophila Sk Channel (Dsk) In Courtship Memory, Ahmad N. Abou Tayoun, Claudio Pikielny, Patrick J. Dolph

Dartmouth Scholarship

A role for SK channels in synaptic plasticity has been very well-characterized. However, in the absence of simple genetic animal models, their role in behavioral memory remains elusive. Here, we take advantage of Drosophila melanogaster with its single SK gene (dSK) and well-established courtship memory assay to investigate the contribution of this channel to memory. Using two independent dSK alleles, a null mutation and a dominant negative subunit, we show that while dSK negatively regulates the acquisition of short-term memory 30 min after a short training session, it is required for normal long-term memory 24 h after extended …


Pf19 Encodes The P60 Catalytic Subunit Of Katanin And Is Required For Assembly Of The Flagellar Central Apparatus In Chlamydomonas, Erin E. Dymek, Elizabeth F. Smith Mar 2012

Pf19 Encodes The P60 Catalytic Subunit Of Katanin And Is Required For Assembly Of The Flagellar Central Apparatus In Chlamydomonas, Erin E. Dymek, Elizabeth F. Smith

Dartmouth Scholarship

For all eukaryotic cilia the basal bodies provide a template for the assembly of the doublet microtubules, and intraflagellar transport provides a mechanism for transport of axonemal components into the growing cilium. What is not known is how the central pair of microtubules is nucleated or how their associated polypeptides are assembled. Here we report that the Chlamydomonas pf19 mutation results in a single amino acid change within the p60 catalytic subunit of katanin, and that this mutation prevents microtubule severing activity. The pf19 mutant has paralyzed flagella that lack the central apparatus. Using a combination of mutant analysis, RNAi-mediated …


Heterogeneity In Mitochondrial Morphology And Membrane Potential Is Independent Of The Nuclear Division Cycle In Multinucleate Fungal Cells, John P. Gerstenberger, Patricia Occhipinti, Amy S. Gladfelter Jan 2012

Heterogeneity In Mitochondrial Morphology And Membrane Potential Is Independent Of The Nuclear Division Cycle In Multinucleate Fungal Cells, John P. Gerstenberger, Patricia Occhipinti, Amy S. Gladfelter

Dartmouth Scholarship

In the multinucleate filamentous fungus Ashbya gossypii, nuclei divide asynchronously in a common cytoplasm. We hypothesize that the division cycle machinery has a limited zone of influence in the cytoplasm to promote nuclear autonomy. Mitochondria in cultured mammalian cells undergo cell cycle-specific changes in morphology and membrane potential and therefore can serve as a reporter of the cell cycle state of the cytoplasm. To evaluate if the cell cycle state of nuclei in A. gossypii can influ


Complete Genome Sequence Of Clostridium Clariflavum Dsm 19732, Javier A. Izquierdo, Lynne Goodwin, Karen W. Davenport, Hazuki Teshima Jan 2012

Complete Genome Sequence Of Clostridium Clariflavum Dsm 19732, Javier A. Izquierdo, Lynne Goodwin, Karen W. Davenport, Hazuki Teshima

Dartmouth Scholarship

Clostridium clariflavum is a Cluster III Clostridium within the family Clostridiaceae isolated from thermophilic anaerobic sludge (Shiratori et al, 2009). This species is of interest because of its similarity to the model cellulolytic organism Clostridium thermocellum and for the ability of environmental isolates to break down cellulose and hemicellulose. Here we describe features of the 4,897,678 bp long genome and its annotation, consisting of 4,131 protein-coding and 98 RNA genes, for the type strain DSM 19732.


Reverse Protection Assay: A Tool To Analyze Transcriptional Rates From Individual Promoters, Yan O. Zubo, Victor V. Kusnetsov, Thomas Börner, Karsten Liere Dec 2011

Reverse Protection Assay: A Tool To Analyze Transcriptional Rates From Individual Promoters, Yan O. Zubo, Victor V. Kusnetsov, Thomas Börner, Karsten Liere

Dartmouth Scholarship

Transcriptional activity of entire genes in chloroplasts is usually assayed by run-on analyses. To determine not only the overall intensity of transcription of a gene, but also the rate of transcription from a particular promoter, we created the Reverse RNase Protection Assay (RePro): in-organello run-on transcription coupled to RNase protection to define distinct transcript ends during transcription. We demonstrate successful application of RePro in plastid promoter analysis and transcript 3' end processing.


Planning Combinatorial Disulfide Cross-Links For Protein Fold Determination, Fei Xiong, Alan M Friedman, Chris Bailey-Kellogg Nov 2011

Planning Combinatorial Disulfide Cross-Links For Protein Fold Determination, Fei Xiong, Alan M Friedman, Chris Bailey-Kellogg

Dartmouth Scholarship

Fold recognition techniques take advantage of the limited number of overall structural organizations, and have become increasingly effective at identifying the fold of a given target sequence. However, in the absence of sufficient sequence identity, it remains difficult for fold recognition methods to always select the correct model. While a native-like model is often among a pool of highly ranked models, it is not necessarily the highest-ranked one, and the model rankings depend sensitively on the scoring function used. Structure elucidation methods can then be employed to decide among the models based on relatively rapid biochemical/biophysical experiments.


Additive Functions In Boolean Models Of Gene Regulatory Network Modules, Christian Darabos, Ferdinando Ferdinando Di Cunto, Marco Tomassini, Jason H. Moore Nov 2011

Additive Functions In Boolean Models Of Gene Regulatory Network Modules, Christian Darabos, Ferdinando Ferdinando Di Cunto, Marco Tomassini, Jason H. Moore

Dartmouth Scholarship

Gene-on-gene regulations are key components of every living organism. Dynamical abstract models of genetic regulatory networks help explain the genome’s evolvability and robustness. These properties can be attributed to the structural topology of the graph formed by genes, as vertices, and regulatory interactions, as edges. Moreover, the actual gene interaction of each gene is believed to play a key role in the stability of the structure. With advances in biology, some effort was deployed to develop update functions in Boolean models that include recent knowledge. We combine real-life gene interaction networks with novel update functions in a Boolean model. We …


Erect Wing Facilitates Context-Dependent Wnt/Wingless Signaling By Recruiting The Cell-Specific Armadillo-Tcf Adaptor Earthbound To Chromatin, Nan Xin, Hassina Benchabane, Ai Tian, Kerrie Nguyen, Lindsay Klofas, Yashi Ahmed Nov 2011

Erect Wing Facilitates Context-Dependent Wnt/Wingless Signaling By Recruiting The Cell-Specific Armadillo-Tcf Adaptor Earthbound To Chromatin, Nan Xin, Hassina Benchabane, Ai Tian, Kerrie Nguyen, Lindsay Klofas, Yashi Ahmed

Dartmouth Scholarship

During metazoan development, the Wnt/Wingless signal transduction pathway is activated repetitively to direct cell proliferation, fate specification, differentiation and apoptosis. Distinct outcomes are elicited by Wnt stimulation in different cellular contexts; however, mechanisms that confer context specificity to Wnt signaling responses remain largely unknown. Starting with an unbiased forward genetic screen in Drosophila, we recently uncovered a novel mechanism by which the cell-specific co-factor Earthbound 1 (Ebd1), and its human homolog jerky, promote interaction between the Wnt pathway transcriptional co-activators B-catenin/Armadillo and TCF to facilitate context-dependent Wnt signaling responses. Here, through the same genetic screen, we find an unanticipated requirement …


Axl2 Integrates Polarity Establishment, Maintenance, And Environmental Stress Response In The Filamentous Fungus Ashbya Gossypii, Jonathan F. Anker, Amy S. Gladfelter Oct 2011

Axl2 Integrates Polarity Establishment, Maintenance, And Environmental Stress Response In The Filamentous Fungus Ashbya Gossypii, Jonathan F. Anker, Amy S. Gladfelter

Dartmouth Scholarship

In budding yeast, new sites of polarity are chosen with each cell cycle and polarization is transient. In filamentous fungi, sites of polarity persist for extended periods of growth and new polarity sites can be established while existing sites are maintained. How the polarity establishment machinery functions in these distinct growth forms found in fungi is still not well understood. We have examined the function of Axl2, a transmembrane bud site selection protein discovered in Saccharomyces cerevisiae, in the filamentous fungus Ashbya gossypii. A. gossypii does not divide by budding and instead exhibits persistent highly polarized growth, and multiple axes …


High Ethanol Titers From Cellulose By Using Metabolically Engineered Thermophilic, Anaerobic Microbes, D. Aaron Argyros, Shital A. Tripathi, Trisha F. Barrett, Stephen R. Rogers, Lawrence F. Feinberg, Daniel G. Olson, Justin M. Foden, Bethany B. Miller, Lee R. Lynd, David A. Hogsett, Nicky C. Caiazza Sep 2011

High Ethanol Titers From Cellulose By Using Metabolically Engineered Thermophilic, Anaerobic Microbes, D. Aaron Argyros, Shital A. Tripathi, Trisha F. Barrett, Stephen R. Rogers, Lawrence F. Feinberg, Daniel G. Olson, Justin M. Foden, Bethany B. Miller, Lee R. Lynd, David A. Hogsett, Nicky C. Caiazza

Dartmouth Scholarship

This work describes novel genetic tools for use in Clostridium thermocellum that allow creation of unmarked mutations while using a replicating plasmid. The strategy employed counter-selections developed from the native C. thermocellum hpt gene and the Thermoanaerobacterium saccharolyticum tdk gene and was used to delete the genes for both lactate dehydrogenase (Ldh) and phosphotransacetylase (Pta). The Δldh Δpta mutant was evolved for 2,000 h, resulting in a stable strain with 40:1 ethanol selectivity and a 4.2-fold increase in ethanol yield over the wild-type strain. Ethanol production from cellulose was investigated with an engineered coculture of organic acid-deficient engineered strains of …