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Title: Atom distance and interaction between DNA and acetylated histone tails.
Creator: Goordeen, Victoria, Snyder, Patricia Ann
Date Issued: 2013-04-05
PURL: http://purl.flvc.org/fcla/dt/3361087
Subject Headings: Transcription, Genetic, Histones, DNA
Format: Document (PDF)

Title: A Novel Role of the Ankyrin-Binding Motif of L1-Type CAM Neuroglian in Nuclear Import and Transcriptional Regulation of Myc.
Creator: Kakad, Priyanka P., Godenschwege, Tanja A., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: L1-type cell adhesion molecule (L1CAM) plays an essential role in the development of nervous system and is also highly relevant for the progression of diseases such as Alzheimer’s disease, stroke and cancers, some of the leading causes of human mortality. In addition to its canonical role as a plasma membrane protein organizing the cytoskeleton, recent in vitro studies have revealed that transmembrane as well as cytosolic fragments of proteolytically cleaved vertebrate L1CAM translocate to...
Show moreL1-type cell adhesion molecule (L1CAM) plays an essential role in the development of nervous system and is also highly relevant for the progression of diseases such as Alzheimer’s disease, stroke and cancers, some of the leading causes of human mortality. In addition to its canonical role as a plasma membrane protein organizing the cytoskeleton, recent in vitro studies have revealed that transmembrane as well as cytosolic fragments of proteolytically cleaved vertebrate L1CAM translocate to the nucleus and regulate expression of genes involved in DNA post-replication repair, cell cycle control, migration and differentiation. However, little is known about the in vivo function of L1CAM in the adult nervous system. This dissertation research focuses on studying in vivo nuclear translocation and function of L1CAM. Using the Drosophila model system, we first show that the sole Drosophila L1CAM homolog, Neuroglian (Nrg), is proteolytically cleaved by Alzheimer’s associated secretases, similar to L1CAM, and is also translocated to the nucleus in the adult nervous system. Subsequently, we have shown that the deletion of highly conserved Ankyrin binding domain or FIGQY motif disrupts nuclear import. Further experiments have revealed that the nuclear translocation of Nrg is in fact regulated by the phosphorylation of the FIGQY motif. Importantly, our studies also show transgenic expression of full-length Nrg or the intracellular domain of Nrg resulted in increased myc expression, which is associated with increased sensitivity to oxidative stress and reduced life span. On the other hand, deletion of the FIGQY motif or mutations preventing its phosphorylation led to decrease in myc expression. In summary, we have identified a novel role for the highly conserved Ankyrin binding domain in nuclear translocation and transcriptional regulation of the Drosophila myc oncogene, which is of high relevance to neurodegenerative diseases and cancer associated with oxidative stress.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00013076
Subject Headings: Cell adhesion molecules., Myc proteins., Transcription, Genetic., Transcription factors, Gene expression., Ankyrins., Translocation, Genetic.
Format: Document (PDF)

Title: Characterization of Group B Sox genes in the development of Drosophila nervous system.
Creator: Singh, Shweta, Dawson-Scully, Ken, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Sox proteins all contain a single ~70 amino acid High Mobility Group (HMG) DNA-binding domain with strong homology to that of Sry, the mammalian testisdetermining factor. In Drosophila melanogaster, there are four closely related members of the B group, Dichaete (D), Sox Neuro (Sox N), Sox 21a, and Sox 21b that each exhibit ~90% sequence identity within the HMG domain.The previous study has shown that Dichaete plays a major role in embryonic nervous system development and is expressed in...
Show moreSox proteins all contain a single ~70 amino acid High Mobility Group (HMG) DNA-binding domain with strong homology to that of Sry, the mammalian testisdetermining factor. In Drosophila melanogaster, there are four closely related members of the B group, Dichaete (D), Sox Neuro (Sox N), Sox 21a, and Sox 21b that each exhibit ~90% sequence identity within the HMG domain.The previous study has shown that Dichaete plays a major role in embryonic nervous system development and is expressed in several clusters of neurons in the brain, including intermingled olfactory LNs and central-complex neurons strongly expressed in local interneuron of the olfactory system. However, little is known about the possible expression and functions of the related group B Sox genes in the larval and adult brain. In particular, it is unclear if Sox N may function along with Dichaete in controlling the development or physiology of the adult olfactory system. Our data suggests Sox N potential role in the elaboration of the olfactory circuit formation.
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Date Issued: 2017
PURL: http://purl.flvc.org/fau/fd/FA00004907, http://purl.flvc.org/fau/fd/FA00004907
Subject Headings: Drosophila melanogaster--Physiology., Transcription factors., Gene expression., Genetic transcription., Cell cycle., Neural stem cells.
Format: Document (PDF)

Title: Activators and repressors of transcription: using bioinformatics approaches to analyze and group human transcription factors.
Creator: Savitskaya, Ala., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Transcription factors are macromolecules that are involved in transcriptional regulation by interacting with specific DNA regions, and they can cause activation or silencing of their target genes. Gene regulation by transcriptional control explains different biological processes such as development, function, and disease. Even though transcriptional control has been of great interest for molecular biology, much still remains unknown. This study was designed to generate the most current list...
Show moreTranscription factors are macromolecules that are involved in transcriptional regulation by interacting with specific DNA regions, and they can cause activation or silencing of their target genes. Gene regulation by transcriptional control explains different biological processes such as development, function, and disease. Even though transcriptional control has been of great interest for molecular biology, much still remains unknown. This study was designed to generate the most current list of human transcription factor genes. Unique entries of transcription factor genes were collected and entered into Microsoft Office 2007 Access Database along with information about each gene. Microsoft Office 2007 Access tools were used to analyze and group collected entries according to different properties such as activator or repressor record, or presence of certain protein domains. Furthermore, protein sequence alignments of members of different groups were performed, and phylogenetic trees were used to analyze relationship between different members of each group. This work contributes to the existing knowledge of transcriptional regulation in humans.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/1930495
Subject Headings: Transcription factors, Genetic transcription, Regulation, Cellular signal transduction, DNA microarrays, Bioinformatics
Format: Document (PDF)

Title: Synaptic Rearrangements and the Role of Netrin-Frazzled Signaling in Shaping the Drosophila Giant Fiber Circuit.
Creator: Lloyd, Brandon N., Murphey, Rodney K., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: In the developing CNS, presynaptic neurons often have exuberant overgrowth and form excess (and overlapping) postsynaptic connections. Importantly, these excess connections are refined during circuit maturation so that only the appropriate connections remain. This synaptic rearrangement phenomenon has been studied extensively in vertebrates but many of those models involve complex neuronal circuits with multiple presynaptic inputs and postsynaptic outputs. Using a simple escape circuit in...
Show moreIn the developing CNS, presynaptic neurons often have exuberant overgrowth and form excess (and overlapping) postsynaptic connections. Importantly, these excess connections are refined during circuit maturation so that only the appropriate connections remain. This synaptic rearrangement phenomenon has been studied extensively in vertebrates but many of those models involve complex neuronal circuits with multiple presynaptic inputs and postsynaptic outputs. Using a simple escape circuit in Drosophila melanogaster (the giant fiber circuit), we developed tools that enabled us to study the molecular development of this circuit; which consists of a bilaterally symmetrical pair of presynaptic interneurons and postsynaptic motorneurons. In the adult circuit, each presynaptic interneuron (giant fiber) forms a single connection with the ipsilateral, postsynaptic motorneuron (TTMn). Using new tools that we developed we labeled both giant fibers throughout their development and saw that these neurons overgrew their targets and formed overlapping connections. As the circuit matured, giant fibers pruned their terminals and refined their connectivity such that only a single postsynaptic connection remained with the ipsilateral target. Furthermore, if we ablated one of the two giant fibers during development in wildtype animals, the remaining giant fiber often retained excess connections with the contralateral target that persisted into adulthood. After demonstrating that the giant fiber circuit was suitable to study synaptic rearrangement, we investigated two proteins that might mediate this process. First, we were able to prevent giant fibers from refining their connectivity by knocking out highwire, a ubiquitin ligase that prevented pruning. Second, we investigated whether overexpressing Netrin (or Frazzled), part of a canonical axon guidance system, would affect the refinement of giant fiber connectivity. We found that overexpressing Netrin (or Frazzled) pre- & postsynaptically resulted in some giant fibers forming or retaining excess connections, while exclusively presynaptic (or postsynaptic) expression of either protein had no effect. We further showed that by simultaneously reducing (Slit-Robo) midline repulsion and elevating Netrin (or Frazzled) pre- & postsynaptically, we significantly enhanced the proportion of giant fibers that formed excess connections. Our findings suggest that Netrin-Frazzled and Slit-Robo signaling play a significant role in refining synaptic circuits and shaping giant fiber circuit connectivity.
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Date Issued: 2016
PURL: http://purl.flvc.org/fau/fd/FA00004758, http://purl.flvc.org/fau/fd/FA00004758
Subject Headings: Drosophila melanogaster--Cytogenetics., Genetic transcription., Transcription factors., Cellular signal transduction., Cellular control mechanisms., Cell receptors.
Format: Document (PDF)

Title: Molecular characterization of ARID and DDT domain.
Creator: MacDonald, Emmanuel., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Transcriptional regulation of genes is vital to cell success making it an important aspect of research. Transcriptional regulation can occur in many ways; transcription factors bind to the promoter region and block transcription, disrupt an activator protein, or interact with histones to lead to higher order chromatin. Plant HomeoDomain can recognize and bind to different methylation states of histone tails. PHD proteins use other functional regions to carry out functions. Two associated...
Show moreTranscriptional regulation of genes is vital to cell success making it an important aspect of research. Transcriptional regulation can occur in many ways; transcription factors bind to the promoter region and block transcription, disrupt an activator protein, or interact with histones to lead to higher order chromatin. Plant HomeoDomain can recognize and bind to different methylation states of histone tails. PHD proteins use other functional regions to carry out functions. Two associated domains having DNA-binding capacity were characterized in this study; the ARID domains of JARID1A and JARID1C and the DDT domains of BAZ1A, BAZ1B and BAZ2A. These genes are important because of their roles in various diseases such as cancer. The consensus sequences for BAZ1A-DDT is GGACGGRnnGG, GnGAGRGCRnnGGnG, RAGGGGGRnG and CRYCGGT. Consensus sequences for BAZ1B-DDT were CGnCCAnCTTnTGGG and YGCCCCTCCCCnR. Consensus sequences for BAZ2A-DDT were TACnnAGCnY and CnnCCRGCnRTGnYY. Consensus sequence for JARID1A-ARID was GnYnGCGYRCYnCnG. Consensus sequences for JARID1C-ARID was RGGRGCCRGGY.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2705077
Subject Headings: Genetic transcription, Regulation, Transcription factors, Zinc-finger proteins, Synthesis, Cellular signal transduction, Gene expression
Format: Document (PDF)

Title: Netrin-Frazzled signaling instructs synaptogenesis and plasticity at an identified central synapse in Drosophila.
Creator: Orr, Brian, Murphey, Rodney K., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The classic guidance molecules, Netrin and its receptor Frazzled (Fra), dictate the strength of synaptic connections in the giant fiber system (GFS) of Drosophila melanogaster by regulating gap junction localization in the pre-synaptic terminal. In Netrin mutant animals the synaptic coupling between a giant interneuron and the jump motor neuron was weakened. Dye-coupling between these two neurons was severely compromised or absent. These mutants exhibited anatomically and physiologically...
Show moreThe classic guidance molecules, Netrin and its receptor Frazzled (Fra), dictate the strength of synaptic connections in the giant fiber system (GFS) of Drosophila melanogaster by regulating gap junction localization in the pre-synaptic terminal. In Netrin mutant animals the synaptic coupling between a giant interneuron and the jump motor neuron was weakened. Dye-coupling between these two neurons was severely compromised or absent. These mutants exhibited anatomically and physiologically defective synapses between the giant fiber (GF) and tergotrochanteral motor neuron (TTMn). In cases where Netrin mutants displayed apparently normal synaptic anatomy, half of the specimens exhibited physiologically defective synapses. Dye-coupling between the giant fiber and the motor neuron was reduced or eliminated, suggesting that gap junctions were disrupted in the Netrin mutants. When we examined the gap junctions with antibodies to Shaking-B Innexin (ShakB), they were significantly decreased or absent in the pre-synaptic terminal of the mutant GF. This data is the first to show that Netrin and Frazzled regulate placement of gap junctions pre-synaptically at a central synapse. In the Drosophila Giant Fiber System, we demonstrate a mechanism that ensures the monoinnervation of two homologous motor neurons by two homologous interneurons. In a scenario where both interneurons could synapse with both motor neuron targets, each interneuron exclusively synapsed with only one target and the circuit functions at normal physiological levels. This innervation pattern depended on the ratio of netrin-to-frazzled expression. When Netrin was over expressed in the system, shifting the ratio in favor of Netrin, both interneurons synapsed with both target motor neurons and physiological function was reduced. This resulted in the polyinnervationof a single target. In contrast, when Frazzled was over expressed in the system, one interneuron innervated both targets and excluded the remaining interneuron from making any synaptic contact. This resulted in a single interneuron mono-innervating both motor neurons and physiological function was mutant. The orphaned interneuron made no synaptic contact with either motor neuron target. Physiological function was only normal when the Netrin-Frazzled ratio was at endogenous levels and each GF monoinnervated one motor neuron. When we examined the gap junctions at this synapse in experimental animals, there was a significant reduction of gap junction hemichannels in the presynaptic terminal of axons that deviated from normal innervation patterns. While the synapse dyecoupled, the reduction in gap junction hemichannels reduced function in the circuit.
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Date Issued: 2013
PURL: http://purl.flvc.org/fau/fd/FA0004041
Subject Headings: Cellular control mechanisms, Cellular signal transduction, Drosophila melanogaster -- Cytogenetics, Genetic transcription, Transcription factors
Format: Document (PDF)

Title: Comprehensive study of the ZAD family of zinc finger transcription factors in Drosophila melanogaster.
Creator: Krystel, Joseph., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The zinc finger associated domain (ZAD) family of transcription factors from Drosophila melanogaster is not well described in the literature, in part because it is very difficult to study by traditional mutagenesis screens. Bioinformatic studies indicate this is due to overlapping functions remaining after a recent evolutionary divergence. I set out to use in vitro-binding techniques to identify the characteristics of the ZAD family and test this theory. I have constructed glutathione S...
Show moreThe zinc finger associated domain (ZAD) family of transcription factors from Drosophila melanogaster is not well described in the literature, in part because it is very difficult to study by traditional mutagenesis screens. Bioinformatic studies indicate this is due to overlapping functions remaining after a recent evolutionary divergence. I set out to use in vitro-binding techniques to identify the characteristics of the ZAD family and test this theory. I have constructed glutathione S-transferase (GST)-ZAD domain chimeric proteins for use in pull down protein binding assays,and GST-Zinc finger (ZnF) array domain chimera for electrophoretic mobility shift assays (EMSA). Protein binding assays indicated two putative conserved interactors, similar to the analogous KRAB system in mammals. ... Competitive bindings were carried out to show a specificity of binding conferred by the identified conserved positions. While the consensus binding sites show relatively few similarities, the predicted target genes identified by the consensus binding sites show significant overlap. The nature of this overlap conforms to the known characteristics of the ZAD family but points to a more positive selection to maintain conservation of function.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3355627
Subject Headings: Cellular signal transduction, Drosophila melanogaster, Cytogenetics, Transcription factors, Zinc-finger proteins, Synthesis, Genetic transcription, Regulation, Gene expression
Format: Document (PDF)

Title: Elucidation of the features of the zinc finger associated domain (ZAD) family of transportation factors in Drosophila melanogaster.
Creator: Krystel, Joseph., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The zinc finger associated domain (ZAD) containing family of transcription factors is not well described in the literature, in part because it is very difficult to study by mutagenesis. We used in vitro-binding techniques to identify characteristics of the ZAD family, by constructing glutathione Stransferase (GST)-ZAD domain chimeric proteins for use in protein binding assays, and GST-Zinc finger array domain chimera for binding site selections. Protein binding assays indicated a possible...
Show moreThe zinc finger associated domain (ZAD) containing family of transcription factors is not well described in the literature, in part because it is very difficult to study by mutagenesis. We used in vitro-binding techniques to identify characteristics of the ZAD family, by constructing glutathione Stransferase (GST)-ZAD domain chimeric proteins for use in protein binding assays, and GST-Zinc finger array domain chimera for binding site selections. Protein binding assays indicated a possible shared cofactor, as seen in the analogous KRAB system in mammals. DNA binding assays have provided a consensus binding sequence for five of the ZAD proteins, consistent with previously reported work on ZAD and unpublished work on mammalian transcription factors. Research is ongoing with an additional ~50 ZAD proteins to more fully map the binding characters of ZAD proteins.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/186768
Subject Headings: Cellular signal transduction, Drosophila melanogaster, Cytogenetics, Transcription factors, Zinc-finger proteins, Synthesis, Genetic transcription, Regulation, Gene expression
Format: Document (PDF)

Title: Identification of longitudinals lacking (LOLA) target genes in Drosophila melanogaster.
Creator: Qureshi, Bazila., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Longitudinals lacking gene (LOLA) is a transcription factor that is involved in a variety of axon guidance decisions in Drosophila melanogaster nervous system. Besides having a role as an epigenetic silencer and in the programmed cell death in Drosophila's ovary, this gene is also an example of complex transcription unit. LOLA is a transcription repressor and can generate 17 DNA - binding isoforms, through alternative splicing, each containing distinct zinc-finger proteins. This unique...
Show moreLongitudinals lacking gene (LOLA) is a transcription factor that is involved in a variety of axon guidance decisions in Drosophila melanogaster nervous system. Besides having a role as an epigenetic silencer and in the programmed cell death in Drosophila's ovary, this gene is also an example of complex transcription unit. LOLA is a transcription repressor and can generate 17 DNA - binding isoforms, through alternative splicing, each containing distinct zinc-finger proteins. This unique DNAbinding binding sequence to which LOLA-ZFP binds has been determined for four of the lola isoforms F, J, P and K. Also, bioinformatics' tool approach has been taken to identify the target genes that are regulated by these four LOLA splice variants. Future work will be done for the five other LOLA isoforms to categorize their putative DNA-binding sequences and subsequently their protein interactions.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2684893
Subject Headings: Transcription factors, Cellular signal transduction, Zinc-finger proteins, Synthesis, Genetic transcription, Regulation, Drosophila melanogaster, Cytogenetics, Gene expression
Format: Document (PDF)

Title: Highwire's characterization and signaling roles in Drosophila central synapse formation.
Creator: Rowland, Kimberly Diane., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The assembly and maintenance of central synapses is a complex process, requiring myriad genes and their products. Highwire is a large gene containing a RING domain, characteristic of ubiquitin E3 ligases. Highwire has been shown to restrain axon growth and control synaptogenesis at a peripheral synapse. Here I examine the roles of Highwire at a central synapse in the adult Drosophila Giant Fiber System (GFS). Highwire is indeed necessary for proper axonal growth as well as synaptic...
Show moreThe assembly and maintenance of central synapses is a complex process, requiring myriad genes and their products. Highwire is a large gene containing a RING domain, characteristic of ubiquitin E3 ligases. Highwire has been shown to restrain axon growth and control synaptogenesis at a peripheral synapse. Here I examine the roles of Highwire at a central synapse in the adult Drosophila Giant Fiber System (GFS). Highwire is indeed necessary for proper axonal growth as well as synaptic transmission in the GFS. Differences arise between the central synapse and the neuromuscular junction (NMJ), where highwire was initially characterized : expresion from the postsynaptic cell can rescue highwire synaptic defects, which is not seen at the NMJ. In addition, a MAP kinase signaling pathway regulated by highwire at the NMJ has differing roles at a central synapse. Wallenda MAPK can rescue not only the highwire anatomical phenotype but also the defects seen in transmission. Another distinction is seen here : loss of function basket and Dfos enhance the highwire anatomical phenotype while expression of dominant negative basket and Dfos suppress the highwire phenotype. As a result we have compared the signaling pathway in flies and worms and found that the NMJ in the two organisms use a parallel pathway while the central synapse uses a distinct pathway.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3352826
Subject Headings: Cellular control mechanisms, Cellular signal transduction, Cell differentiation, Gene expression, Genetic transcription, Transcription factors, Drosophila melanogaster, Cytogenetics
Format: Document (PDF)

Title: Characterization of SNAG-zinc finger protein (ZFP) transcription factors.
Creator: Chiang, Cindy Chung-Yue., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Transcriptional regulation is an important area of research due to the fact that it leads to gene expression. Transcription factors associated with the regulation can either be activators or repressors of target genes, acting directly or with the aid of other factors. A majority of transcriptional repressors are zinc finger proteins (ZFPs) which bind to specific DNA sequences. The Snail/Gfi (SNAG) domain family, with members such as Slug, Smuc, Snail, and Scratch, are transcriptional...
Show moreTranscriptional regulation is an important area of research due to the fact that it leads to gene expression. Transcription factors associated with the regulation can either be activators or repressors of target genes, acting directly or with the aid of other factors. A majority of transcriptional repressors are zinc finger proteins (ZFPs) which bind to specific DNA sequences. The Snail/Gfi (SNAG) domain family, with members such as Slug, Smuc, Snail, and Scratch, are transcriptional repressors shown to play a role in various diseases such as cancer. The SNAG transcription factors contain a conserved SNAG repression domain and DNA binding domain zinc fingers. The specific DNA sequences to which each SNAG-ZFP binds, as well as a general consensus -TGCACCTGTCCGA, have been determined. Also, putative protein-protein interactions in which the Slug domain participates has been identified via binding assays. All these results contribute to better understanding of SNAG-ZFP functions.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/186676
Subject Headings: Zinc-finger proteins, Synthesis, Metalloproteins, Synthesis, Genetic transcription, Regulation, Cellular signal transduction, Gene expression
Format: Document (PDF)

Title: A comprehensive study of mammalian SNAG transcription family members.
Creator: Chiang, Cindy Chung-Yue., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Transcriptional regulation by the family of SNAG (Snail/Gfi-1) zinc fingers has been shown to play a role in various developmental states and diseases. These transcriptional repressors have function in both DNA- and protein-binding, allowing for multiple interactions by a single family member. This work aims to characterize the SNAG members Slug, Smuc, Snail, Scratch, Gfi-1, Gfi-1B, and IA-1 in terms of both DNA-protein and protein-protein interactions. The specific DNA sequences to which the...
Show moreTranscriptional regulation by the family of SNAG (Snail/Gfi-1) zinc fingers has been shown to play a role in various developmental states and diseases. These transcriptional repressors have function in both DNA- and protein-binding, allowing for multiple interactions by a single family member. This work aims to characterize the SNAG members Slug, Smuc, Snail, Scratch, Gfi-1, Gfi-1B, and IA-1 in terms of both DNA-protein and protein-protein interactions. The specific DNA sequences to which the zinc finger regions bind were determined for each member, and a general consensus of TGCACCTGTCCGA, was developed for four of the members. Via these studies, we also reveal thebinding affinities of E-box (CANNTG) sequences to the members, since this core is found for multiple members' binding sites. Additionally, protein-protein interactions of SNAG members to other biological molecules were investigated. The Slug domain and Scratch domain have unknown function, yet through yeast two-hybrid screening, we were able to determine protein interaction partners for them as well as for other full length SNAG members. These protein-interacting partners have suggested function as corepressors during transcriptional repression. The comprehensive information determined from these studies allow for a better understanding of the functional relationship between SNAG-ZFPs and other genes. The collected data not only creates a new profile for each member investigated, but it also allows for further studies to be initiated from the results.
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Date Issued: 2012
PURL: http://purl.flvc.org/fcla/dt/3342041
Subject Headings: Cellular signal transduction, Zinc-finger proteins, Synthesis, Metalloproteins, Synthesis, Genetic transcription, Regulation
Format: Document (PDF)

Title: Highwire coordinates synapse formation and maturation by regulating both a map kinase cascade and the ability of the axon to respond to external cues in the giant fiber system of Drosophila Melanogaster.
Creator: Borgen, Melissa A., Murphey, Rodney K., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The ubiquitin ligase Highwire is responsible for cell-autonomously promoting synapse formation in the Drosophila Giant Fiber system. highwire mutants show defects in synaptic function and extra branching at the axon terminal, corresponding to transient branching that occur in the course of giant synapse formation during metamorphosis. The MAP kinase pathway, including Wallenda and JNK/Basket, plus the transcription factor Jun, act to suppress synaptic function and axon pruning in a dosage...
Show moreThe ubiquitin ligase Highwire is responsible for cell-autonomously promoting synapse formation in the Drosophila Giant Fiber system. highwire mutants show defects in synaptic function and extra branching at the axon terminal, corresponding to transient branching that occur in the course of giant synapse formation during metamorphosis. The MAP kinase pathway, including Wallenda and JNK/Basket, plus the transcription factor Jun, act to suppress synaptic function and axon pruning in a dosage sensitive manner, suggesting different molecular mechanisms downstream of the MAP kinase pathway govern function and pruning. A novel role for Highwire is revealed, regulating the giant fiber axon’s ability to respond to external cues regulated by Fos. When expression of the transcription factor Fos is disrupted in the post-synaptic TTMn or surrounding midline glia of highwire mutants, the giant fiber axons show a marked increase in axon overgrowth and midline crossing. However, synaptic function is rescued by the cell nonautonomous manipulation of Fos, indicating distinct mechanisms downstream of Highwire regulating synaptic function and axon morphology.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004081, http://purl.flvc.org/fau/fd/FA00004081
Subject Headings: Cell differentiation, Cellular control mechanisms, Cellular signal transduction, Drosophila melanogaster -- Cytogenetics, Gene expression, Genetic transcription
Format: Document (PDF)

Title: Heterologous expression and purification of cell function components -: an effort towards developing an antigen-capture ELISA diagnostics for metastatic cancers.
Creator: Irvine, Michael., Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: Metastatic cancers are problematic because they spread throughout the body. A crucial step in cancer metastasis is the separation of the cancer cells from their surrounding normal cells. This occurs due to suppression or destruction of cell adhesion molecules such as E-cadherin, occludin, and various claudins. The Snail and Slug transcription factors play a direct role in suppressing these cell adhesion molecules through their SNAG repression domain. We explored the possibility of developing...
Show moreMetastatic cancers are problematic because they spread throughout the body. A crucial step in cancer metastasis is the separation of the cancer cells from their surrounding normal cells. This occurs due to suppression or destruction of cell adhesion molecules such as E-cadherin, occludin, and various claudins. The Snail and Slug transcription factors play a direct role in suppressing these cell adhesion molecules through their SNAG repression domain. We explored the possibility of developing an ELISA diagnostics capable of detecting soluble E-cadherin, occludin, and claudin fragments in the serum of cancer patients. Using several bioinformatics tools, unique extracellular antigenic sequences were identified on claudins-1, 4, 16, occludin, and E-cadherin. These sequences were cloned as GST fusion proteins, expressed, and purified in large quantities to raise antibodies. In parallel, expression profiling of metastatic cancer cell lines was carried out to derive a correlation between Snail-Slug expression and suppression of cell adhesion molecules.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/369191
Subject Headings: Cellular signal transduction, Extracellular matrix proteins, Genetic transcription, Research, Metalloproteinases, Inhibitors
Format: Document (PDF)

Title: Molecular characterization of a subset of KRAB-ZFPs.
Creator: Chamoun, Alain., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: There are approximately 20,000 genes in the human genome. Around 2% of these genes code for transcriptional repressors known as KRAB-ZFPs. It is already known that Zinc-Finger Proteins contain two main functional domains at either end of the polypeptide. In today's database, you will find a KRAB (Kruppell-associated Box) domain at one end and a tandem array of Zinc-finger repeats at the other end. The carboxyl terminal tandem Zinc-finger repeats function as sequence-specific DNA-binding...
Show moreThere are approximately 20,000 genes in the human genome. Around 2% of these genes code for transcriptional repressors known as KRAB-ZFPs. It is already known that Zinc-Finger Proteins contain two main functional domains at either end of the polypeptide. In today's database, you will find a KRAB (Kruppell-associated Box) domain at one end and a tandem array of Zinc-finger repeats at the other end. The carboxyl terminal tandem Zinc-finger repeats function as sequence-specific DNA-binding domains. The amino terminal KRAB domain serves as a repressor domain, which will recruit a co-repressor termed KAP-1 (KRAB Associated Protein-1). Located in between these two domains is a region of uncharacterized DNA referred to as the "Linker Region". This thesis will explore the DNA-binding domains of 6 known KRAB-ZFPs, as well as utilize the linker regions to derive an evolutionary history for this superfamily.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2684313
Subject Headings: Zinc-finger proteins, Synthesis, Metalloproteins, Synthesis, Genetic transcription, Regulation, Gene expression
Format: Document (PDF)

Title: Study of the Coupling Between Transcription and mRNA Processing Utilizing a Novel Bcl-x Mini-gene.
Creator: Devanney, Sean C., Caputi, Massimo, Florida Atlantic University
Abstract/Description: The Bel family of genes are fundamental to the apoptotic mechanism. Bcl-x a member of this family, is alternatively spliced to create two main isoforms a long (Bcl-xL) and a short (Bcl-xS) variant. The long form exhibits anti-apoptotic activity, while the short form favors apoptosis. The proper balance of expression of these two isoforms is crucial for several developmental processes such as thymic selection and neural reshaping. A number of cancer types have been shown to over-express the...
Show moreThe Bel family of genes are fundamental to the apoptotic mechanism. Bcl-x a member of this family, is alternatively spliced to create two main isoforms a long (Bcl-xL) and a short (Bcl-xS) variant. The long form exhibits anti-apoptotic activity, while the short form favors apoptosis. The proper balance of expression of these two isoforms is crucial for several developmental processes such as thymic selection and neural reshaping. A number of cancer types have been shown to over-express the long form, thereby granting them some protection from apoptosis. To study the transcriptional and post-transcriptional mechanisms regulating gene expression, the Bcl-x gene has been utilized. A complex mini-gene construct has been create in order to monitor the effects that promoter sequences, 5'UTR and 3'UTR's have on mRNA splicing, RNA export, stability and translation. Abundant evidence exists indicating that RNA processing events such as transcription, splicing and export are coupled, yet the mechanisms and factors involved in regulating these processes are poorly understood. The mini-gene is identical to the endogenous gene with the exception of a deletion to the 50Kb intron and the addition of a tag to differentiate the mini-gene product from the endogenous mRNA and protein. This novel system allows for the study of transcriptional and post-transcriptional mechanisms regulating gene expression from RNA biogenesis on to the protein level.
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Date Issued: 2007
PURL: http://purl.flvc.org/fau/fd/FA00000741
Subject Headings: Genetic transcription, Proteins--Synthesis, Messenger RNA, Gene expression, Oncogenes--Research
Format: Document (PDF)

Title: Identification and characterization of mutations in the Drosophila mitochondrial translation elongation factor iconoclast.
Creator: Trivigno, Catherine F., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Mitochondrial disorders resulting from defects in oxidative phosphorylation are the most common form of inherited metabolic disease. Mutations in the human mitochondrial translation elongation factor GFM1 have recently been shown to cause the lethal pediatric disorder Combined Oxidative Phosphorylation Deficiency Syndrome (COXPD1). Children harboring mutations in GFM1 exhibit severe developmental, metabolic and neurological abnormalities. This work describes the identification and extensive...
Show moreMitochondrial disorders resulting from defects in oxidative phosphorylation are the most common form of inherited metabolic disease. Mutations in the human mitochondrial translation elongation factor GFM1 have recently been shown to cause the lethal pediatric disorder Combined Oxidative Phosphorylation Deficiency Syndrome (COXPD1). Children harboring mutations in GFM1 exhibit severe developmental, metabolic and neurological abnormalities. This work describes the identification and extensive characterization of the first known mutations in iconoclast (ico), the Drosophila orthologue of GFM1. Expression of human GFM1 can rescue ico null mutants, demonstrating functional conservation between the human and fly proteins. While point mutations in ico result in developmental defects and death during embryogenesis, animals null for ico survive until the second or third instar larval stage. These results indicate that in addition to loss-of-function consequences, point mutations in ico appear to produce toxic proteins with antimorphic or neomorphic effects. Consistent with this hypothesis, transgenic expression of a mutant ICO protein is lethal when expressed during development and inhibits growth when expressed in wing discs. In addition, animals with a single copy of an ico point mutation are more sensitive to acute hyperthermic or hypoxic stress. Removal of the positively-charged tail of the protein abolishes the toxic effects of mutant ICO, demonstrating that this domain is necessary for the harmful gain-of-function phenotypes observed in ico point mutants., Further, expression of GFP-tagged constructs indicates that the C-terminal tail enhances ectopic nuclear localization of mutant ICO, suggesting that mislocalization of the protein may play a role in the antimorphic effects of mutant ICO. Taken together, these results illustrate that in addition to loss-of-function effects, gain-of-function effects can contribute significantly to the pathology caused by mutation in mitochondrial translation elongation factors.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2705081
Subject Headings: Drosophila melanogaster, Cytogenetics, Mutation (Biology), Mitochondrial DNA, Cell metabolism, Cellular signal transduction, Oxidation, Physiological, Genetic transcription, Regulation
Format: Document (PDF)

Title: The RNA Binding Protein SRSF1 modulates Immune and Cancer pathways by regulating MyD88 transcription.
Creator: Ritchie, Anastasia, Caputi, Massimo, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Medicine
Abstract/Description: Serine/Arginine splicing factor 1 (SRSF1), a member of the Serine/Arginine rich (SR) RNA-binding proteins (RBPs) family, regulates mRNA biogenesis at multiple steps and is deregulated in cancer and autoimmune diseases. Preliminary studies show that members of the SR protein family play a role in cellular transcription. We investigated SRSF1’s role in cellular gene transcription utilizing time-course RNA-Seq and nuclear run-on assays, validating a subset of genes transcriptionally regulated...
Show moreSerine/Arginine splicing factor 1 (SRSF1), a member of the Serine/Arginine rich (SR) RNA-binding proteins (RBPs) family, regulates mRNA biogenesis at multiple steps and is deregulated in cancer and autoimmune diseases. Preliminary studies show that members of the SR protein family play a role in cellular transcription. We investigated SRSF1’s role in cellular gene transcription utilizing time-course RNA-Seq and nuclear run-on assays, validating a subset of genes transcriptionally regulated following SRSF1 overexpression. Pathway analysis showed that genes in the TNF/IL17 pathways were enriched in this dataset. Furthermore, we showed that MyD88, a strong activator of TNF transcription through transcription factors NF-κB and AP-1, is a primary target of SRSF1’s transcriptional activity. We propose that SRSF1 activates the transcription factors NF-κB and AP-1 through MyD88 pathway. SRSF1 overexpression regulates several genes that are deregulated in malignancies and immune disease, suggesting a role for SRSF1’s transcriptional activity in oncogenesis and immune response regulation.
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Date Issued: 2020
PURL: http://purl.flvc.org/fau/fd/FA00013569
Subject Headings: RNA-Binding Proteins, Serine-Arginine Splicing Factors, Cancer, Autoimmune diseases, Transcription, Genetic, RNA, Messenger, Myeloid Differentiation Factor 88.
Format: Document (PDF)

Title: Presynaptic Determinants of Synaptic Strength and Energy Efficiency at Drosophila Neuromuscular Junctions.
Creator: Lu, Zhongmin, Macleod, Gregory, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Changes in synaptic strength underlie synaptic plasticity, the cellular substrate for learning and memory. Disruptions in the mechanisms that regulate synaptic strength closely link to many developmental, neurodegenerative and neurological disorders. Release site probability (PAZ) and active zone number (N) are two important presynaptic determinants of synaptic strength; yet, little is known about the processes that establish the balance between N and PAZ at any synapse. Furthermore, it is...
Show moreChanges in synaptic strength underlie synaptic plasticity, the cellular substrate for learning and memory. Disruptions in the mechanisms that regulate synaptic strength closely link to many developmental, neurodegenerative and neurological disorders. Release site probability (PAZ) and active zone number (N) are two important presynaptic determinants of synaptic strength; yet, little is known about the processes that establish the balance between N and PAZ at any synapse. Furthermore, it is not known how PAZ and N are rebalanced during synaptic homeostasis to accomplish circuit stability. To address this knowledge gap, we adapted a neurophysiological experimental system consisting of two functionally differentiated glutamatergic motor neurons (MNs) innervating the same target. Average PAZ varied between nerve terminals, motivating us to explore benefits for high and low PAZ, respectively. We speculated that high PAZ confers high-energy efficiency. To test the hypothesis, electrophysiological and ultrastructural measurements were made. The terminal with the highest PAZ released more neurotransmitter but it did so with the least total energetic cost. An analytical model was built to further explore functional and structural aspects in optimizing energy efficiency. The model supported that energy efficiency optimization requires high PAZ. However, terminals with low PAZ were better able to sustain neurotransmitter release. We suggest that tension between energy efficiency and stamina sets PAZ and thus determines synaptic strength. To test the hypothesis that nerve terminals regulate PAZ rather than N to maintain synaptic strength, we induced sustained synaptic homeostasis at the nerve terminals. Ca2+ imaging revealed that terminals of the MN innervating only one muscle fiber utilized greater Ca2+ influx to achieve compensatory neurotransmitter release. In contrast, morphological measurements revealed that terminals of the MN inner vating multiple postsynaptic targets utilized an increase in N to achieve compensatory neurotransmitter release, but this only occurred at the terminal of the affected postsynaptic target. In conclusion, this dissertation provides several novel insights into a prominent question in neuroscience: how is synaptic strength established and maintained. The work indicates that tension exists between energy efficiency and stamina in neurotransmitter release likely influences PAZ. Furthermore, PAZ and N are rebalanced differently between terminals during synaptic homeostasis.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004519, http://purl.flvc.org/fau/fd/FA00004519
Subject Headings: Drosophila melanogaster--Nervous system., Drosophila melanogaster--Cytogenetics., Fruit-flies--Development., Fruit-flies--Nervous system., Genetic transcription., Transcription factors., Cellular signal transduction., Cellular control mechanisms., Myoneural junction.
Format: Document (PDF)

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Florida Atlantic University (7)	+ -
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