Dissertations / Theses on the topic 'Drosophila models'
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Zhang, Yan. "Implementation of anti-apoptotic peptide aptamers in cell and "in vivo" models of Parkinson's disease." Thesis, Lyon, École normale supérieure, 2012. http://www.theses.fr/2012ENSL0788.
Full textParkinson’s disease is considered as the second most common neurodegenerative disease. Although the cause of the progressive cell loss of PD remains unclear to date, programmed cell death, inflammation and autophagy due to oxidative stress, gene mutations or protein aggregations within DA neuron have been suggested as potential causes. Peptide aptamers are small combinatorial proteins, with a variable loop inserted into a scaffold protein, human thioredoxin, hTRX. They are used to facilitate dissection of signaling networks by modulating specific protein interactions and functions. Two peptide aptamers were identified by functional selection which inhibit Bax-dependent cell death in mammalian models. One peptide aptamer (Apta-32) is binding two paralogues involved in endocytotic trafficking T32. The second peptide aptamer (Apta-34) is binding to a target "T34", a pro-apoptotic protein mediating apoptosis emanating from the nucleus. The work of my PhD thesis aimed to investigate the anti-apoptotic function of our two peptide aptamers in different PD models including cell model (in vitro), brain tissue slice and D. melanogaster (in vivo) ; in particular their impact on neuron survival after exposure to specific toxins. Two major toxins were applied in this work, 6-hydroxindopamine (6-OHDA) and Paraquat, a commonly used pesticide. Our observations indicated that Drosophila expressing Apta-32 in all neurons showed more resistance 48h after treatment with Paraquat, compared to drosophila expressing Apta-34 or TRX. Another study revealed a defect in phagocytosis of apoptotic bodies in drosophila embryo’s expressing Apta-32 in macrophage, suggesting Apta-32 could be involved in, and perhaps interfere with, the process of autophagy. This suggests that Apta-32 could protect against paraquat induced autophagy in neurons
Hobani, Yahya Hasan. "Metabolomic analyses of Drosophila models for human renal disease." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3222/.
Full textVargas, Miguel. "Nutrient response and aging in invertebrate models." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/nutrient-response-and-aging-in-invertebrate-models(3fccf140-7906-4fad-9892-b8957dc44a04).html.
Full textSnigdha, Kirti. "Study of Tumor Development Using Drosophila melanogaster Models." University of Dayton / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1591210557481631.
Full textXun, Zhiyin. "Understanding Parkinson's disease through proteome analyses of Drosophila melanogaster models." [Bloomington, Ind.] : Indiana University, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3344612.
Full textTitle from PDF t.p. (viewed Oct. 7, 2009). Source: Dissertation Abstracts International, Volume: 70-02, Section: B, page: 0993. Adviser: David E. Clemmer. Includes supplementary digital materials.
Michel, Claire Hélène Marie. "Investigating inflammation in a Drosophila model of Alzheimer's disease." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608998.
Full textGirard, Victor. "Understanding lipid droplet biogenesis in the central nervous system of Drosophila models of Parkinson's disease." Thesis, Lyon, 2020. http://www.theses.fr/2020LYSEN083.
Full textNeurodegenerative disorders are a worldwide leading cause of disability. Several neurodegenerative disorders including Parkinson's disease (PD) are associated with lipid storage dysregulation in the brain. In particular, the storage of lipids in cytoplasmic organelles, called lipid droplets (LDs), has recently emerged as important mechanism of the stress response. Several labs including ours, found that LD accumulation in glia may promote neuronal survival in condition of oxidative stress. Interestingly, in the context of neurodegeneration, neurons can also accumulate LDs. The contribution of neuronal and glial cells LDs to neurodegeneration remains a topic of debate. During my PhD, I investigated the mechanisms and consequences of LD accumulation in neurons and glia in two Drosophila models of PD. PD is characterized by the accumulation of misfolded alpha-synuclein (aSyn) in neuronal cytoplasmic inclusions. Interestingly, aSyn contains a lipid-binding domain that shares structural similarities with LD-binding proteins such as perilipins and aSyn can bind synthetic LD in vitro and induces LD accumulation in yeast by a mechanism that remains unclear. I found that expression of aSyn in association with perilipin impairs LD homeostasis leading to accumulation of LDs in Drosophila photoreceptor neurons. Interestingly, I observed that aSyn co-localizes with perilipins on LD surface in both Drosophila photoreceptor neurons and human neuroblastoma cells. I thus proposed that aSyn by associating with perilipins stabilize LD and by this mean promote LD accumulation. Finally, modulating LD content in photoreceptor impacts aSyn resistance to proteinase K suggesting that LDs are involved in pathological conversion of aSyn. Glial cells are early sensor of central nervous system injuries that accumulate LDs in response to neuronal stress to protect neurons from damages associated with lipid peroxidation. We found that Split-ends (Spen), an RNA binding protein previously identified as a glial pro-survival factor during development, maintains LD homeostasis in adult glial cell. In addition, expression of spen was associated with resistance to paraquat-induced neurotoxicity, a pesticide associated with increased risk of PD in human epidemiologic studies. These results suggest that Spen-mediated lipid metabolism functions is important for neuroprotection in PD.Collectively the results of my thesis provide new evidences for the formation of LDs in both neurons and glial cells and their contribution in the progression of PD pathology
Ferlito, Valentina Claudia. "Evaluating the potential for neurodegenerative disease models in juvenile Drosophila melanogaster." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28834.
Full textPage, Richard Mark Donald. "Pathways of amyloid-β neurotoxicity in a Drosophila model of Alzheimer's disease." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612858.
Full textMacLeod, Ian. "A Drosophila model of familial encephalopathy with neuroserpin inclusion bodies." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611439.
Full textNehrkorn, Johannes [Verfasser], and Andreas [Akademischer Betreuer] Herz. "Olfactory learning in Drosophila : learning from models / Johannes Nehrkorn. Betreuer: Andreas Herz." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/108250498X/34.
Full textLimmer, Stéfanie. "Study of host pathogen relationships in intestinal infection models of Drosophila melanogaster." Strasbourg, 2010. http://www.theses.fr/2010STRA6103.
Full textS. Marcescens fed to the fly are killing in 6-8 days. To better understand the host factors implicated in the infection process we performed an ill vivo genome-wide RNAi (RNA interference) screen. This screen was realized in collaboration with the Penninger lab (Vienna). A secondary screen on the candidate genes that have vertebrate homolgs (mouse or human) was carried out using a midgut-specific driver to express the RNAi hairpin constructs. Amongst the genes that showed, in addition to the primary screen, a phenotype in the intestine specific screen, were several members of the JAK-STAT pathway. We were able to show that the JAK-STAT pathway is needed to control the level of compensatory proliferation of ISCs during the infectious process. P. Aeruginosa kills the flies within 8-\0 days upon ingestion. A strong proliferation of the bacteria in the hemolymph induces the two pathways of the humoral systemic immune response, Toll and Immune Deficiency (IMD). Phagocytosis is also needed for host defense. Bacteria mutant for the gene rhIR are less virulent. RhIR mutant bacteria just regain their virulence in flies deficient for phagocytosis. Our results show that RhIR is needed to counteract the cellular immune response, but not the humoral immune response
Afzal, Mahmood Qurat-ul-ain. "Investigation of the effects of MFN2 mutations in cellular and Drosophila models." Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/10760/.
Full textIrving, Andrew David. "General methods for large biological networks applied to fruit fly models." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/general-methods-for-large-biological-networks-applied-to-fruit-fly-models(5eb3812e-f2dc-488b-bba4-fa0f094d4776).html.
Full textKrench, Megan Attardo. "Investigating toxicity in Drosophila models of Huntington's Disease and Huntington's Disease-Like 2." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/103211.
Full textCataloged from PDF version of thesis.
Includes bibliographical references (pages 247-264).
The polyglutamine diseases are the most common form of inherited neurodegenerative disorders. Each of the polyglutamine diseases stems from the same underlying cause: a CAG expansion mutation in the coding region of a gene. This gives rise to a protein with an expanded glutamine repeat stretch. Despite the fact that all polyglutamine diseases are caused by the same type of mutation, the CAG expansion in different genes gives rise to different diseases, with differentially vulnerable neuronal populations and distinct pathologies. One of the most well-known polyglutamine disorders is Huntington's disease (HD), which results from a CAG repeat expansion in the huntingtin (Htt) gene. HD is characterized by psychiatric symptoms, cognitive decline, and movement disturbances, especially chorea. Interestingly, some presumed HD patients exhibited HD-like symptoms and characteristic striatal degeneration, but did not harbor a mutation in Htt. This led to the discovery of the Huntington's disease-like (HDL) disorders. One such disorder is Huntington's disease-like 2 (HDL2). Recent studies identified a specific polyglutamine protein hypothesized to contribute to HDL2 pathology. Given the similarities between HD and HDL2 patients, I used Drosophila to model these two genetically distinct disorders to compare polyglutamine-induced toxicity. This work represents the first time HDL2 has been modeled in Drosophila, and the first characterization of HDL2 polyglutamine protein pathology. My investigation highlights many distinctions between expanded Htt and HDL2 polyglutamine proteins. Importantly, my research demonstrates that nuclear localization of the polyglutamine protein is critical to disease pathogenesis in HDL2, but not HD. I also present the results from an in vivo RNAi screen to search for novel suppressors of toxicity in our HD and HDL2 models. Analyzing top RNAi suppressors from both models indicates different pathogenic pathways are at play in these two polyglutamine diseases, but some mechanisms may be shared. We conclude that while HD and HDL2 have similar clinical profiles, distinct pathogenic mechanisms contribute to the two neurodegenerative disorders.
by Megan Krench.
Ph. D. in Neuroscience
Moens, Thomas Grover. "Molecular mechanisms of pathogenesis in Drosophila models of C9orf72 mutation associated ALS/FTD." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10046295/.
Full textPolo, Carla Cristina 1987. "Caracterização molecular de domínios funcionais de miosinas de drosophila melanogaster." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314549.
Full textDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-20T10:58:02Z (GMT). No. of bitstreams: 1 Polo_CarlaCristina_M.pdf: 4286137 bytes, checksum: cf12a2b67d90255468d1906d719759a3 (MD5) Previous issue date: 2012
Resumo: As miosinas pertencem a uma família de proteínas motoras que através da hidrólise de ATP são capazes de se movimentarem pelas fibras de actina. Sua estrutura é dividida em três domínios principais: motor, responsável pela hidrólise do ATP; regulador, envolvido na ligação de cadeias leves de calmodulina e a cauda, que tem papel essencial na mediação de interações com cargas celulares, como organelas, ácidos nucleicos e outras proteínas. O organismo modelo para insetos, Drosophila melanogaster, possui 11 miosinas pertencentes a 8 classes sendo que informações funcionais e bioquímicas são escassas, e estruturais, inexistentes. Apesar dos grandes avanços obtidos nos estudos de miosinas humanas, as miosinas de inseto ainda são pouco caracterizadas não havendo estudos comparativos, como por exemplo, para a determinação de conservação de parceiros moleculares entre os diferentes filos da classificação de Lineu. Neste contexto, foram selecionados os seguintes domínios de inseto para caracterização molecular: quinase da miosina III, cauda globular da miosina V e FERM da miosina XV. A partir do cDNA da pupa e adulto do inseto foram amplificados os fragmentos de genes de interesse e clonados em vetor de clonagem, pGEM T-easy, e posteriormente de expressão, pET28a e pET28aSUMO. Após testes em diversas condições no sistema bacteriano, as construções cauda globular da miosina V (GLOB_2 e GT-f) e domínio FERM-f da miosina XV foram obtidos na fração solúvel e com rendimento suficiente para estudos estruturais. O protocolo de expressão em larga escala assim como de purificação foram estabelecidos para cada uma dessas construções. Estudos biofísicos por aSEC, DLS, CD e SAXS foram realizados para a proteína GT-f da miosina V, mostrando a proteína monomérica com alto conteúdo de hélices-alfa corroborando as análises in silico e com as caudas globulares de miosinas ortólogas já descritas. Além disso, sua termoestabilidade foi avaliada com Tm de 46 ºC e que sua estabilidade é alterada pela adição de alguns ligantes, mas não pela força iônica como verificado para a cauda globular da miosina Va humana. A estrutura a baixa resolução da GT-f foi determinada pelos experimentos de SAXS, mostrou uma proteína monomérica com forma alongada (Dmax =100 Å). Para a construção FERM-f, apesar do sucesso alcançado no protocolo de expressão e purificação, a amostra permaneceu polidispersa e com uma estrutura random coil, inviabilizado futuros experimentos. Acredita-se que a ausência do domínio MyTH4, gerou a perda de estabilidade do domínio FERM-f e será necessária a clonagem dos dois domínios fusionados para garantir a estabilidade estrutural e funcional
Abstract: Myosins belong to a motor protein superfamily that uses the ATP hydrolysis to move along actin filaments. Its structural architecture comprises three main domains: motor, responsible for ATP hydrolysis; regulator, which binds calmodulin light chains; and tail, responsible for cellular cargoes binding. Drosophila melanogaster, an insect model, has 11 myosins belonging to 8 different myosin classes; however functional and biochemical data are scanty, and, structural, absent. Although the great advances on investigating human and yeast myosins with the elucidation of molecular partners and molecular mechanisms involved in signaling, there are no comparative studies among different phyla. Therefore, in order to gain insights into insect myosins, in silico analysis were performed and some domains like kinase (myosin III), globular tail (myosin V), and FERM (myosin XV) were selected for biophysical and structural studies. From pupa and adult cDNAs, the target genes were amplified and cloned into pGEM- T-easy, pET28a and pET28aSUMO vectors. After expressions tests, the myosin V globular tail constructs, GLOB_2 and GT-f, and myosin XV FERM-f were obtained in soluble fraction and in sufficient amounts for structural studies. aSEC, DLS, CD e SAXS biophysical studies were performed to myosin V GT-f, showing that the protein is monomeric with predominance of alpha-helix in accordance with the in silico atomic model. The stability of GT-f was assessed with a Tm of 46 ºC and some molecules are able to increase the stability, while the ionic strength has no difference like was observed for the human globular tail of myosin Va. The low resolution structure determined by SAXS experiments confirmed the monomeric state and its elongated molecular shape (Dmax = 100 Å). The FERM-f construct, although the purification and expression protocol were standardized, the sample remained polydisperse with a random coil structure, disabling other biophysical experiments. It is supposed that the absence of the MyTH4 domain in the FERM-f domain results in loss of stability, and cloning and expression of fused domains will be necessary to guarantee structural and functional stability
Mestrado
Bioquimica
Mestre em Biologia Funcional e Molecular
Laurent, Stefan. "Statistical inference of complex demographic models in Drosophila melanogaster and two wild tomato species." Diss., lmu, 2011. http://nbn-resolving.de/urn:nbn:de:bvb:19-126410.
Full textMartinez, Zarate A. "Parkinson's disease-associated proteins : studying their role in mitophagy with cellular and Drosophila models." Thesis, University of Liverpool, 2017. http://livrepository.liverpool.ac.uk/3007480/.
Full textSolomon, Daniel Adam. "Mechanisms of G4C2 derived dipeptide repeat protein toxicity in Drosophila models of C9ALS/FTD." Thesis, King's College London (University of London), 2018. https://kclpure.kcl.ac.uk/portal/en/theses/mechanisms-of-g4c2-derived-dipeptide-repeat-protein-toxicity-in-drosophila-models-of-c9alsftd(fe890a3c-a4a0-42c7-b2fc-7780889fc2b9).html.
Full textVarga, Scott J. "An Analysis of the Potential Rescue Effects of Optogenetic Approaches in Drosophila Models of Parkinson's Disease." Ohio University Honors Tutorial College / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1366924643.
Full textWaghmare, Indrayani. "Investigation of Altered Cell-Cell Interactions and Signaling Mechanisms in Drosophila Tumor Models." University of Dayton / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1467810236.
Full textSchindler, Franziska [Verfasser]. "Analysis of mutant huntingtin aggregation and toxicity in Drosophila models of Huntington’s disease / Franziska Schindler." Berlin : Freie Universität Berlin, 2017. http://d-nb.info/1127046225/34.
Full textDulcis, Davide. "The Drosophila and Manducahearts as models for studying the role of innervation in cardiac function." Diss., The University of Arizona, 2004. http://hdl.handle.net/10150/280603.
Full textNerelius, Charlotte. "Protein misfolding and amyloid formation : strategies for prevention /." Uppsala : Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, 2009. http://epsilon.slu.se/200941.pdf.
Full textFluegel, Megan L. "Establishment of a Drosophila model of Niemann-Pick type C disease /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/5065.
Full textBaldwin, Katie. "A survey of axonal transport function and motor behaviour in Drosophila models of amyotrophic lateral sclerosis." Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/12248/.
Full textLuheshi, Leila Mohamed. "Mutational analysis of the aggregation and toxicity of the amyloid beta peptide in a Drosophila model of Alzheimer's Disease." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612965.
Full textLiu, Beinan. "Iron mediated amyloid beta toxicity and oxidative stress in a Drosophila melanogaster model of Alzheimer's disease." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608978.
Full textStapper, Zeenna A. [Verfasser], and Bernd [Akademischer Betreuer] Bukau. "The role of redox homeostasis in Drosophila models of Aß aggregation / Zeenna A. Stapper ; Betreuer: Bernd Bukau." Heidelberg : Universitätsbibliothek Heidelberg, 2019. http://d-nb.info/1181106125/34.
Full textLin, Ivy Carmen. "The Effects of Various Pharmacological Agents on the Sleep and Locomotor Activity of Drosophila Models of ALS." Thesis, The University of Arizona, 2013. http://hdl.handle.net/10150/297689.
Full textAl, Zamal Faiyaz. "Relating the expression-based and sequence-based estimates of regulation in the gap gene system of Drosophila melanogaster." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112321.
Full textYong, Li [Verfasser]. "Adrenergic signaling in the fruit fly Drosophila melanogaster : establishment and analysis of models for obesity and diabetes / Li Yong." Kiel : Universitätsbibliothek Kiel, 2018. http://d-nb.info/116965276X/34.
Full textFetherson, Rebecca A. "An experimental and genomic approach to the regulation of alternative pre-mRNA splicing in Drosophila rnp-4f." Connect to this document online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=miami1114713461.
Full textTitle from first page of PDF document. Document formatted into pages; contains [1], ix, 75 p. : ill. Includes bibliographical references (p. 69-75).
Bergkvist, Liza. "Amyloid-β and lysozyme proteotoxicity in Drosophila : Beneficial effects of lysozyme and serum amyloid P component in models of Alzheimer’s disease and lysozyme amyloidosis." Doctoral thesis, Linköpings universitet, Kemi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-137452.
Full textDureau, Maxime. "Characterization and simulation of the mechanical forces that control the process of Dorsal Closure during Drosophila melanogaster embryogenesis." Thesis, Lyon, École normale supérieure, 2015. http://www.theses.fr/2015ENSL0999/document.
Full textThe work presented here aims at characterizing and simulating the mechanical forces involved in the process of Dorsal Closure in the organism Drosophila melanogaster, an embryonic process. In particular, Dorsal Closure participates in the acquisition of the final form of the embryo. Therefore, the work presented here aims at fathoming our knowledge on tissues mechanics, as well as their role in the acquisition of shape. The tissues involved in Dorsal Closure are the epidermis and the amnioserosa. At this stage of development, the epidermis surrounds almost all the embryo. Nevertheless, the amnioserosa still covers a large area of the dorsal side called dorsal hole. Hence, Dorsal Closure aims at shutting this hole and joining the lateral sides of the epidermis, in a process similar to wound healing. In order to fuse the two sides of the epidermis on the dorsal line, the epidermis must be drawn dorsalward. This movement is driven by the amnioserosa on the one hand, and by the dorsalmost row of the epidermis (called Leading Edge cells) on the other hand. The latter first form a transcellular Actin Cable around the dorsal hole. The cable, contracting, will reduce the area of the dorsal hole, covered by the amnioserosa. Second, the Leading Edge cells emit protrusions that will attach to the opposite Leading Edge and drag it toward themselves, untill the two sides of the epidermis fuse. These protrusions have a limited range, hence the dragging and fusion only take place at the ends of the dorsal hole (called canthi), where the distance between the two Leading Edges is small enough. The Amnioserosa also drags the epidermis toward the dorsal line. Its cells produce a contractile network. Interstingly, Amnioserosa cells see the area of their top side (apical side) vary in a periodic way. Although these variations have been widely studied, their role in Dorsal Closure remains unknown. This PhD aims at improving our knowledge of the mechanical concepts involved in these oscillations, and to build a physical model representing these movements. The work presented here also studies the movements of the Leading Edge cells, in order to understand the effect of the Actin Cableon the dynamics of Dorsal Closure. In order to study the cells movements and the role of the tissues involved in Dorsal Closure, an algorithm was developped, allowing to detect the cells edges, their position, as well as those of their vertices (multiple junction between three or four cells) and to track them over time. A user interface was also developped, in order to facilitate the adjustment of the parameters allowing the detection, as well as the correction of possible errors. Various dynamical models were then built following the lagrangian approach. The systems of equations deriving from the Euler-Lagrange equations were numerically solved, and their predictions compared to the biological data extracted thanks to the algorithm presented earlier, following the least square approach. The model validation was performed thanks to the autocorrelation function test. Finally, the Leading Edge dynamics was studied characterising the cellular movements at the interface between the epidermis and the amnioserosa. Wild type embryos dynamics were compared to those of mutated embryos showing specific defects in the Actin Cable formation. The results presented in this manuscript allow a better understanding of the processes involved in in Amnioserosa cells oscicllations. They also give clues on their biological characteristics. Finally, they assess the role of the actin cable in this process similar to wound healing
Haye, Alexandre. "Modélisation de l'évolution temporelle de l'expression des gènes sur la base de données de puces à ADN: application à la drosophile." Doctoral thesis, Universite Libre de Bruxelles, 2011. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209904.
Full textPremièrement, l’observation des données d’expression utilisées nous a conduits à approfondir l’étude des phénomènes survenant lors des changements de stades de développement de la drosophile. Dans ce but, deux méthodes de détection automatique de ces changements ont été développées et appliquées aux données temporelles disponibles sur le développement d’eucaryotes supérieurs. Elles ont également été appliquées à des données temporelles relatives à des perturbations externes de bactéries. Cette étude à montré qu’une formulation mathématique simple permettait de retrouver les instants expérimentaux où une perturbation ou un changement de stade de développement est observé, à partir uniquement des profils d’expression. Par ailleurs, la réponse à une perturbation externe s’avère non distinguable d’une succession de stades de développement, sur la base des seuls profils temporels d’expression.
Deuxièmement, en raison des dimensions du problème constitué par les données d’expression de plusieurs milliers de gènes et de l’impossibilité de distinguer le rôle dans la régulation des gènes qui présentent des profils d’expression similaires, il s’est avéré nécessaire de classifier les gènes selon leurs profils d’expression. En nous basant sur les résultats obtenus lors de la détection des stades de développement, la démarche suivie est de regrouper les gènes qui présentent des profils temporels d’expression aux comportements similaires non seulement au cours de la série temporelle complète, mais également dans chacun des stades de développement. Dans cette optique, trois distances ont été proposées et utilisées dans une classification hiérarchique des données d’expression de la drosophile.
Troisièmement, des structures de modèles linéaires et non linéaires ainsi que des méthodes d’estimation et de réduction paramétriques ont été développées et utilisées pour reproduire les données d’expression du développement de la drosophile. Les résultats de ce travail ont montré qu’avec une structure de modèle linéaire simple, la reproduction des profils expérimentaux était excellente et que, dans ce cas, le réseau de régulation génique de la drosophile pouvait se contenter d’une faible connectivité (en moyenne 3 connexions par classe de gènes) et ce, sans hypothèse a priori. Toutefois, les modèles linéaires ont ensuite sérieusement été remis en question par des analyses de robustesse aux perturbations paramétriques et de stabilité des profils après extrapolation dans le temps. Dès lors, quatre structures de modèles non linéaires et cinq méthodes de réduction paramétrique ont été proposées et utilisées pour concilier les critères de reproduction des données, de robustesse et de stabilité des réseaux identifiés. En outre, ces méthodes de modélisation ont été appliquées à un sous-ensemble de 20 gènes impliqués dans le développement musculaire de la drosophile et pour lesquels 36 interactions ont été validées expérimentalement, ainsi qu’à des profils synthétiques bruités. Nous avons pu constater que plus de la moitié des connexions et non-connexions sont retrouvées par trois modèles non linéaires. Les résultats de cette étude ont permis d’éliminer certaines structures de modèle et méthodes de réduction et ont mis en lumière plusieurs directions futures à suivre dans la démarche de modélisation des réseaux de régulation génique.
Doctorat en Sciences de l'ingénieur
info:eu-repo/semantics/nonPublished
Smith, Aaron. "Vertex model approaches to epithelial tissues in developmental systems." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:4d19f232-764c-4e27-bca9-d2ede0ec2db9.
Full textNiehus, Sebastian. "Développement d’un modèle d’étude génétique des relations hôtes- parasites entre un parasite intracellulaire obligatoire, la microsporidie Tubulinosema ratisbonensis et l’organisme modèle Drosophila melanogaster." Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAJ137.
Full textMore than 150 years of Microsporidia research led to a basic understanding of many aspects of microsporidial biology, yet little is known about the genetic basis and molecular mechanisms of the intimate host-parasite relationship that govern Microsporidia infections.Here, I first report on the detection, prophylaxis, and eradication measures against microsporidial infestations with Tubulinosema ratisbonensis, infecting cultures of Drosophila melanogaster. To date,knowledge about Drosophila host defense against obligate intracellular parasites remained incomplete for lack of good infection models.To this end, I have developed infection models of Drosophila by the microsporidian T. ratisbonensis,both in cell lines and in adults. The work on the cellular infection model encompasses transcriptomics and metabolomics approaches, which aim to attempt both sides of the host-pathogen equation. Finally, I report on the biological roles of glycosylphosphatidyl inositols of Toxoplasma gondii
Plantié, Émilie. "Utilisation d'un modèle drosophile pour l'identification de marqueurs moléculaires responsables des symptômes musculaires et cardiaques de la maladie de Steinert." Thesis, Clermont-Ferrand 1, 2016. http://www.theses.fr/2016CLF1MM19/document.
Full textThe most common muscular dystrophy found in adults, Steinert disease or Myotonic Dystrophy Type 1 (DM1) is caused by an unstable CTG repeat expansion in the 3’ untranslated region of the Dystrophia Myotonica Protein Kinase (DMPK) gene. This multisystemic disease, affecting particularly skeletal muscles and the heart, is called a spliceopathy because it involves the sequestration of the MBNL1 splicing factor by the expanded CUG-carrying transcripts and the stabilization of the CELF1 splicing factor. The misbalance of these two factors is responsible for splicing defects that cause most of the disease symptoms, like myotonia, conduction defects and arrhythmia but also insulin resistance, respectively associated to missplicing of Clcn1, SCN5A and IR. Moreover, DM1 toxicity is also associated to splice-independent deregulations but their link to disease symptoms remain poorly understood. To identify transcriptional deregulations independent of splicing and associated to disease progression and severity, we generated new DM1 Drosophila models with increasing number of CTG repeats. These larval models recapitulated the main DM1 muscular symptoms such as hypercontractility and foci formation and allowed us identifying gene deregulations independent of splicing. Among them, Gbe1 coding for a glycan branching enzyme is attenuated in the DM1 context in a CTG-repeat dependant manner and could participate in the severity of muscle phenotypes. To better understand the causes of cardiac symptoms that represent the second cause of death and affecting 80% of DM1 patients, we took advantage of our DM1 inducible Drosophila model and performed phenotypic analyses on the heart of adult flies expressing: 960 CTG specifically in the heart (Hand>DM1 960 ), a RNAi for the Drosophila MBNL1 orthologue (Muscleblind, Mbl) or overexpressing the CELF1 orthologue (Bruno-3, Bru3). These DM1 adult models display conduction abnormalities, arrhythmicity (fibrillation) and dilated cardiomyopathy (DCM). Thus, these three pathogenic contexts recapitulated collectively the main DM1 cardiac symptoms and prompted us to perform transcriptional profiling to identify symptom’s-associated gene deregulations. To identify new molecular actors responsible for the DM1 associated heart defects, we performed cardiac cell-specific transcriptional analyses by RNA-sequencing, using TU-tagging technique. Then, we selected deregulated candidate genes that could be linked to the particular observed phenotypes and ranked depending on their conservation and deregulation level. Among them, increased expression of Straightjacket (Stj), the CACNA2D4 orthologue, encoding a subunit of voltage- dependent calcium channel results in fibrillation and conduction defects, thus mimicking cardiac symptoms found in DM1 960 and Bru-3 gain of function contexts in which it was up- regulated. Whether identified candidates are deregulated in DM1 patients displaying cardiac abnormalities remains to be tested
Badji, Aisha. "A PCOS-like Drosophila Melanogaster model." Thesis, Högskolan i Skövde, Institutionen för hälsa och lärande, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-17845.
Full textSarkar, Ankita. "Drosophila Eye Model to Study Neurodegeneration." University of Dayton / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1537311159395439.
Full textGupta-Bosch, Tripti. "Deciphering intrinsic and extrinsic machinery underlying collective glia migration using Drosophila as a model organism." Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ009/document.
Full textThe remarkable ability of neurons and glia to undergo long distance and collective migration ensures the final architecture and function of the brain. This is an extremely dynamic process that not only depends on cell interactions, but also on the presence of specific transcription factors in the migrating cells. Adhesion molecules such as classic cadherins and chemoattractants/repellants are known to regulate directional migration, however, how are these pathways regulated is largely unknown. While the role of these molecules controlling cell interactions has been extensively investigated, the signaling cascades that trigger chemotropism are not understood. During the course of my PhD I have analyzed the role of an adhesion molecule and the impact of a chemoattractant receptor regulated by an early transcription factor in the process. The glial chain in a developing Drosophila wing provides an excellent tool to study the molecular pathway underlying collective migration
Voght, Stephen P. "Establishment of a Drosophila model of intestinal sterol absorption and trafficking /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/10303.
Full textMartorell, Aleman Òscar. "Modelling colorectal cancer in Drosophila = Establiment d'un model de càncer colorectal a Drosophila." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/145376.
Full textUn dels càncers més comuns als països desenvolupats és el càncer colorectal (CRC). El terme CRC inclou totes aquelles lesions tumorals que ocorren a l’intestí gros, el recte i l’apèndix. Aquests càncers ocorren per l’acumulació de mutacions al llarg de la vida del pacient. Més d’un 90% de CRC tenen alteracions a la via de Wnt i la seva activació és considerada un dels primers esdeveniments en la progressió del CRC. La segona via de senyalització més alterada durant la progressió del CRC és la via de RTK-RAS amb alteracions activadores de la via presents en un 60% dels casos de CRC (E. R. Fearon, 2011). L'objectiu principal d'aquesta tesi ha estat establir i caracteritzar un model de CRC a Drosòfila per comprendre millor els processos tumorals i alhora identificar nous gens implicats en la progressió del CRC. Per a generar el model de càncer colorectal a l’intestí mig adult vam induir clons mutants pel gen Apc i sobreexpresant la forma activada de Ras, activant així de forma simultània la via de Wnt i EGFR en les mateixes cèl•lules de l’intestí adult de Drosophila. (clons Apc-Ras). Els clons Apc-Ras mostren característiques tumorals tals com: falta de diferenciació, hiperproliferació, falta de polaritat cel•lular. A més a més els clons Apc-Ras mostren un silenciament transcripcional de la via de senyalització de Dpp. Aquest silenciament és essencial per a la progressió dels clons Apc-Ras degut al paper citostàtic de la via de senyalització Dpp. A més a més aquest treball també ha identificat el factor repressor responsable del silenciament de la via de Dpp, el factor de transcripció Mirror. Mitjançant l’expressió de Mirror les cèl•lules Apc-Ras reprimeixen transcripcionalment diversos components de la via de Dpp i evadeixen així el rol citostàtic d’aquesta via. Finalment aquest treball demostra que les proteïnes IRO (homòlogues a Mirror en humans) podrien exercir un rol de similar a Mirror, reduint la resposta a TGF-β/Dpp per part de les cèl•lules tumorals durant la progressió del CRC
Picchio, Lucie. "Mise en place, caractérisation phénotypique et transcriptomique d'un modèle de Drosophilie de la Dystrophie Myotonique de type 1." Thesis, Clermont-Ferrand 1, 2013. http://www.theses.fr/2013CLF1MM15/document.
Full textMyotonic Dystrophy Type 1 (DM1) or Steinert's disease is the most common genetic neuromuscular disorder affecting 1 out of 8000 people worldwide. This multisystemic disease affects particularly the skeletal muscles (myotonia, muscle weakness and wasting) and the heart, which can exhibit various symptoms like conduction disturbances and arrhythmia (auricular fibrillation and flutter). DM1 is caused by an unstable CTG repeat expansion in the 3' non-translated region of the DMPK gene. In healthy individuals, the number of CTG repeats ranges from 5 to 37 whereas DM1 patients carry from 50 to thousands repeats. It is well established that when expanded non-coding repeats aggregate into foci within muscle nuclei and sequester the MBNL1 splicing factor. However, the involvement of the stabilization and accumulation of CUGBP1 following PKC hyper-phosphorylation in the disease is a controversial matter in the DM1 community. Lately, in addition to the disruption of the balance between MBNL1/CUGBP1, several mechanisms were identified as part of the DM1 pathogenesis. Among them, transcription factors perturbations, altered maturation of miRNA, kinases activation… each of them leading eventually to transcriptomic alterations. In order to investigate the effect of toxic repeat expression on phenotypic and transcriptomic alterations, we generated three inducible site-specific Drosophila lines expressing 240, 600 and 960 triplet repeats. We worked in parallel on a mbl (MBNL1 orthologue) knocked-down line and two bru-3 (CUGBP1 orthologue) gain of function lines. When expressed in somatic muscles, CTG repeats lead to altered motility, fiber splitting, reduced fiber size and affected myoblast fusion process in a Mbl and Bru-3 dependent manner. In addition, toxic repeats cause fiber hyper-contraction in a Mbldependentmanner due to dSERCA mis-splicing. Comparative transcriptional profiling performed on larval muscles of different conditions show that mbl attenuation reproduces 70-82% of DM1 transcriptomic deregulations whereas bru-3 gain of function represents 32-53% of transcritomic alterations. Thus Mbl appears as a key factor of transcripts deregulations observed in DM1 muscles. On the contrary, physiologic analyses performed on adult hearts suggest that Bru-3 is a key factor for cardiac phenotypes. Indeed, on one hand, mbl attenuated flies display dilated cardiomyopathy, a symptom barely diagnosed in patients. On the other hand, bru-3 gain of function line and DM1 lines display fibrillation, which evolves withage or repeat size into a phenotype reminiscent of heart insufficiency in patients
Brunk, Kathrin. "A Drosophila model for MCPH1 primary microephaly." Thesis, University of Leeds, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.530842.
Full textPokrzywa, Malgorzata. "A Drosophila Disease-Model for Transthyretin-associated Amyloidosis." Doctoral thesis, Umeå : Umeå University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1677.
Full textLee, Wyan-Ching Mimi. "Characterization of a Drosophila model of Huntington's disease." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/34571.
Full textThis electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references.
Huntington's disease (HD) is an autosomal dominant neurological disorder caused by a polyglutamine (polyQ) repeat expansion in the huntingtin (Htt) protein. The disease is characterized by neurodegeneration and formation of neuronal intracellular inclusions primarily in the striatum and cortex, leading to personality changes, motor impairment, and dementia. To date, the molecular mechanisms that underlie the neurodegenerative process remain to be defined. Development of transgenic Drosophila HD models may facilitate dissection of molecular and cellular pathways that lead to disease pathology and suggest potential strategies for treatment. To explore mutant Htt-mediated mechanisms of neuronal dysfunction, we generated transgenic Drosophila that express the first 548 amino acids of the human Htt gene with either a pathogenic polyglutamine tract of 128 repeats (Htt-Q128) or a nonpathogenic tract of 0 repeats (Htt-QO). Characterization of these transgenic lines indicates formation of cytoplasmic and neuritic Htt aggregates in our Drosophila HD model that sequester other non-nuclear polyQ-containing proteins and block axonal transport.
(cont.) To further explore axonal transport defects in Huntington's disease, we generated Drosophila transgenic strains expressing 588 aa or exon 1 N-terminal fragments of human huntingtin encoding pathogenic (HttQ138) or nonpathogenic (HttQ15) proteins tagged with mRFP and/or eGFP. These transgenic lines enable in vivo imaging of Htt aggregation and trafficking in live Drosophila, providing a unique resource for tracking Htt in real time. Our findings indicate that expression of mutant Htt may impair axonal transport through both aggregate-dependent and -independent means. Finally, to assay the therapeutic effect of expression of an intracellular antibody (intrabody) against Htt, we generated double transgenic lines coexpressing pathogenic Htt (mRFP-HttQ138) with the V12.3 intrabody. Intrabody expression caused suppression of aggregation in both neuronal and non-neuronal cell types, but failed to rescue mutant Htt-mediated cellular dysfunction. In summary, our Drosophila HD model provides an ideal in vivo system for examination of mutant Htt-mediated cellular defects, particularly impairment of axonal transport, and may facilitate rapid development and validation of potential treatments for Huntington's disease.
b y Wyan-Ching Mimi Lee.
Ph.D.
Pratt, Metta. "Drosophila melanogaster as a model to study ciliogenesis." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:09fa66c3-0be0-424e-a02d-8c72377ebc91.
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