Recursos de colección

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Biology - Master's degree

Mostrando recursos 1 - 20 de 72

  1. BiTEs and CAR-Ts : immunotherapy in childhood B-cell acute lymphoblastic leukemia

    Besada, Rana Hany
    B-cell acute lymphoblastic leukemia is the most common pediatric cancer, responsible for the most cancer-related deaths in children. Advances in chemotherapy over the past half-century have steadily increased the remission and survival of children with B-cell acute lymphoblastic leukemia to nearly 90%. However, the problems of minimal residual disease and relapsed and refractory disease persist. Personalized, targeted therapies have improved outcomes among the minority of patients for whom chemotherapy is ineffective. Immunotherapy, specifically bispecific T-cell engaging antibody therapy and chimeric antigen receptor T-cell therapy, has proven an effective treatment for relapsed and refractory B-cell acute lymphoblastic leukemia in children. These...

  2. Interpreting the genome physically in-silico

    Borges-Rivera, Diego (Diego Ramon)
    by Diego Borges-Rivera.

  3. Illuminating the function of a master regulator of Caulobacter crescentus gene expression

    Yuan, Andy H. (Andy Han)
    Bacteria must allocate cellular resources required for transcription in a manner that accommodates the temporally regulated expression of functionally specialized gene products and the constitutive synthesis of stable RNAs required for ribosome biogenesis and translation. The Caulobacter crescentus cell cycle has been well-characterized and represents a powerful model system for studying the regulation of global gene expression patterns and "just-in-time" transcription. Here, we provide evidence that the Caulobacter GcrA protein directly regulates transcription at active promoters of highly expressed genes, particularly those encoding stable RNAs. Furthermore, we demonstrate that GcrA chromosome occupancy is dynamic and subject to epigenetic regulation. Our...

  4. mRNA stability in soma and neurites of cultured neuronal cells

    Srinath, Chetan
    Neurons rely on mRNA localization and local protein synthesis in neurites to regulate synaptic plasticity, axonogenesis and neural signaling. The local regulation of mRNA stability in neurites is poorly understood. To determine mRNA decay rates, we analyzed the subcellular transcriptomes of neural projections and soma of mouse neuronal cells following inhibition of transcription with actinomycin-D. Less stable transcripts were enriched for GU-rich elements in their 3' UTRs. Around 12% of alternative splicing isoform pairs differed in stability, and cassette alternative ("skipped") exons that negatively impact stability are enriched for A-rich sequences. Overall, decay rates were similar across soma and neurites....

  5. mRNA stability in soma and neurites of cultured neuronal cells

    Srinath, Chetan
    Neurons rely on mRNA localization and local protein synthesis in neurites to regulate synaptic plasticity, axonogenesis and neural signaling. The local regulation of mRNA stability in neurites is poorly understood. To determine mRNA decay rates, we analyzed the subcellular transcriptomes of neural projections and soma of mouse neuronal cells following inhibition of transcription with actinomycin-D. Less stable transcripts were enriched for GU-rich elements in their 3' UTRs. Around 12% of alternative splicing isoform pairs differed in stability, and cassette alternative ("skipped") exons that negatively impact stability are enriched for A-rich sequences. Overall, decay rates were similar across soma and neurites....

  6. Genetic screens in vivo using the CRISPR/Cas9 system

    Ellis, Donald Christian
    An unmet and paramount need in the field of cancer research is to rapidly translate basic biological findings to clinically relevant therapeutics for cancer patients. Recent technological advances have generated many innovative applications to cancer biology and in a short time have yielded a wealth of information about putative vulnerabilities across a range of cancers. The proposed work involves the development of a technique to quickly probe potential cancer-specific vulnerabilities in vivo adopting methods used in genetic screens. By harnessing the information obtained from large datasets in vitro and the utility of cutting-edge endogenous mouse models, the general aim of...

  7. Generating single-domain antibodies against fibronectin splice variants

    Peterson, Alexis W
    Here, I describe the process of generating single-domain antibodies which bind to splice variants of fibronectin containing EIIIA or EIIIB. Alpacas were immunized with either purified antigen cocktails, or from the ECM of tumor samples, and antibody libraries were generated. Using these libraries to pan against, I selected for VHH which bind to EIIIA and EIIIB. Since these splice variants are upregulated in tumor angiogenesis and are rarely seen elsewhere in adult tissues, antibodies targeting EIIIA or EIIIB may be of use for imaging tumors and metastases.

  8. teashirt is required for head-versus-tail regeneration polarity in planarians

    Owen, Jared H. (Jared Huntsman)
    Regeneration requires that the identities of new cells are properly specified to replace missing tissues. The Wnt signaling pathway serves a central role in specifying posterior cell fates during planarian regeneration. We identified a gene encoding a homolog of the Teashirt family of zinc finger proteins in the planarian Schmidtea mediterranea to be a target of Wnt signaling in intact animals and at posterior-facing wounds. Inhibition of Smed-teashirt (teashirt) by RNA interference (RNAi) resulted in the regeneration of heads in place of tails, a phenotype previously observed with RNAi of the Wnt pathway genes [beta]-catenin-1, wntl, Dvl-1/2, or wntless. teashirt...

  9. Conformation and dynamics of the mammalian chromosome

    Zhang, Lyndon N. (Lyndon Nuoxi)
    The control of transcription represents a fundamental, initial mechanism by which the regulation of gene expression is implemented. However, while much research has been done on the biochemistry and cellular function of transcription, comparatively little is known on the dynamics of transcriptional mechanisms, their impact on chromatin structure, and concomitant functional consequences. Employing chromatin immunoprecipitation measurements, we report progress towards this goal. We characterize the ensemble chromosome conformation in mouse embryonic stem cells, by measuring interaction, or contact, probabilities between distal genomic loci. We map and describe chromosome loops, consisting of two interacting CTCF sites co-bound by cohesin, that maintain...

  10. Exploring the functional conservation of muscleblind (Mbl) proteins

    Oddo, Julia C. (Julia Christine)
    Muscleblind (Mbl) is an evolutionarily conserved family of proteins involved in many aspects of RNA metabolism, including alternative splicing. Disruption of Muscleblind in several animals lends to a variety of defects and disease, including the multi-systemic disorder Myotonic Dystrophy (DM). Though much is known about the involvement of Muscleblind in DM, there is much basic knowledge of the protein's function to be discovered. We approach this problem by exploring the functional conservation of a diverse subset of Muscleblind homologs. The functions of Muscleblinds from a basal metazoan, Trichoplax adhaerens, a primitive chordate, Ciona intestinalis, and the model organisms, Drosophila melanogaster...

  11. Analysis of NusA's roles in DNA repair and damage tolerance pathways in Escherichia coli

    Zhao, Yimin, S.M. Massachusetts Institute of Technology
    NusA has long known to be a bona fide transcription factor that functions in both termination and antitermination. However, its role in DNA repair and damage tolerance has not been explored until recently. Cohen et al. proposed for the first time that NusA functions as a coupling factor in transcription-coupled translesion synthesis (TC-TLS) and nucleotide excision repair (TCR) processes. A very recent paper by Nudler's lab further supports Cohen's NusA-dependent TCR model. The objectives of the work described here are to gain a deeper understanding of the precise mechanism NusA uses to facilitate DNA repair and damage tolerance.

  12. Structural studies on the LINC complex and Fic-1

    Guo, Xuanzong
    LINC complexes span the nuclear envelope and connect the nucleoskeleton to the cytoskeleton. In 2012, our lab solved the first LINC complex structure, that of SUN domain of human SUN2 bound with KASH1 or KASH2 peptides. In this project testes-specific human SUN proteins (SUN3, SPAG4, and SUNS) were compared to ubiquitously-expressed SUN2. Secondly, fission and budding yeast LINC complexes differ from human ones and were analyzed as well. I was able to confirm SUN-KASH interaction in human and yeast. For structural analysis I explored various expression strategies. Fic-1 is a C. elegans Fic-domain protein with diverse cellular functions. As a...

  13. A flow cytometry-based method for gene expression profiling of CNS cell types

    Luo, Tewei
    In this thesis, I present a technique for profiling gene expression of specific cell types in the central nervous system (CNS), called fluorescence activated nuclei sorting (FANS). FANS utilizes flow cytometry to isolate cell nuclei from CNS subtypes and microarray analysis of nuclear mRNA. When compared to an existing technique, translating ribosome affinity purification, it was found that FANS was able to detect differentially expressed genes between two types of medium spiny neurons in the striatum with similar or higher sensitivity, using transgenic mice with fluorescence proteins labeling the desired cell types. Immunofluorescence experiments were also performed to label cell...

  14. Examination of the nematostella vectensis holobiont by comparative bacterial genomics and metatranscriptomics

    Helbig, Timothy J. (Timothy James)
    Previous work has shown that similar microbial populations are associated with the starlet sea anemone Nematostella vectensis over distinct temporal and geographic locations; however, the functions these bacteria may be performing within their anemone hosts and the mechanisms with which the bacteria may be using to adapt are unknown. To address these issues comparative genomic analysis of ten newly sequenced bacterial isolates from four bacterial populations (Pseudomonas oleovorans, Agrobacterium tumefaciens, Limnobacter thiooxidans and Stappia stellulata) that are associated with Nematostella in the laboratory and/or its natural salt marsh habitat was performed and whole metatranscriptomes of lab-raised N. vectensis were sequenced...

  15. Protein dissection of the Ebola virus glycoprotein

    Schneider, Brian J. (Brian Joseph), 1973-
    by Brian J. Schneider.

  16. Effects of cell growth and a mobile genetic element on propagation of the phages SP16 and SP-beta in Bacillus subtilis

    England, Eleina M. (Eleina Helen Maria)
    Two studies were performed on Bacillus subtilis phages SP16 and SP-beta to characterize the effects of growth and an integrative conjugative element, ICEBs1, respectively. I found that B. subtilis strains are significantly more susceptible to SP16 infection early in the growth phase and less susceptible during exponential growth and as cells approach stationary phase. SP16 makes plaques of different sizes. I found that this variegated plaque size did not seem to breed true. That is, phage from large plaques gave rise to both large and small plaques. On the other hand, phage were difficult to recover from small plaques, indicating...

  17. A computational model for the isothermal assembly of tiled DNA nanostructures

    Steele, Benjamin (Benjamin Craig)
    Complex DNA nanostructures have proven difficult to assemble from starting materials. Inefficient nanostructure assembly constitutes a barrier to the widespread use of DNA nanotechnology and is difficult to investigate experimentally due to the complicated nature of the assembly. This work introduces a type of tile assembly model, the isothermal tile assembly model (iTAM). The iTAM seeks to capture the behavior of assembling DNA tile nanostructures to identify design factors and reaction conditions which improve assembly yields. Simulations using the iTAM model explain the experimental observation that only a narrow range of temperatures permit optimal isothermal assembly of tile-based DNA nanostructures....

  18. CD8⁺ T Cell Response to Influenza Virus

    Doty, Daniel, S.M. Massachusetts Institute of Technology
    The flu is an extremely prevalent and potentially devastating disease, especially dangerous to the very young, the elderly, and to people with compromised immune systems. Influenza has a characteristic course of infection, and is often effectively dispatched by the immune system. The cell-mediated lysis of infected cells is a particularly important step in clearing the infection. Antigen specific CD8+ T lymphocytes are selected and activated in the mediastinal lymph node, proliferate and gain effector function, then migrate to the lungs, where they selectively destroy infected cells. The CD8+ effector population pool undergoes a phase of contraction, when most effector cells...

  19. Investigation of the role of Platelet-Derived Growth Factor (PDGF) in the development of breast carcinomas

    Griffin, Christina Michele
    by Christina Michele Griffin.

  20. Identification and characterization of fullback, a novel posteriorly-expressed Xenopus gene : master's thesis submitted

    Hick, M. Elizabeth, 1974-
    by M. Elizabeth Hick.

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