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Mushakoji, Sumiko. "The process of knowledge construction : a triple parallel wrighting of science, sociology of scientific knowledge and a candidate PhD thesis." Thesis, Loughborough University, 1999. https://dspace.lboro.ac.uk/2134/27066.
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This thesis is an inquiry into the 'process of knowledge construction' in three research domains. These domains are the research into endothelin (a potent vasoconstrictive peptide identified in 1988) in bio-medical science, Sociology of Scientific Knowledge (henceforth, SSK) and the SSK-oriented research of the 'process of knowledge construction' pursued by the Candidate PhD student. The thesis is pursued with a recognition of the self-referential character of itself, that is, reflexivity. Namely, the Candidate's research, including the writing/reading of this thesis, is itself a process of knowledge construction. This recognition is displayed in and through a series of experimental textual forms, 'New Literary Forms (henceforth, NLFs) developed in SSK. Through NLFs, the thesis aims to make itself a wrighting, which connotes "'writing', 'righting' (correcting), and 'wright-ing' (making and working)" (Ashmore 1985, 1989), of the triple parallel process of knowledge construction.
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Gliddon, Judith P. "The processing and interpretation of feedback by PhD candidates." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2007. https://ro.ecu.edu.au/theses/312.
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This study takes a close look at the characteristics of the feedback received by PhD candidates and explores how they then interpret that feedback. Over 200 PhD candidates participated in the study by providing data over a six month period using a custom-built Internet-interfaced database. Each candidate completed a self-concept test both at the beginning and again at the end of this period. In between, they completed an 'e-diary' in which they recorded data about every feedback interaction that they experienced over the six months. From the data collected, the Researcher developed a model showing how feedback is processed and the effect that this process has on PhD candidates.
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Skotvoll, Anniken. "A Study of the Adjustment Process of International PhD Candidates." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for voksnes læring og rådgivningsvitenskap, 2014. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-25950.
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During the adjustment process of a doctor of philosophy (PhD) education, it is understood that international PhD candidates are facing more obstacles than host nationalities, due to arriving to a new culture and without having a relational base in the appurtenant country. The research question to be addressed in this study is: How do international PhD candidates experience the adjustment process in their new research environment during the first semester? Also I will bring in the perspectives of what they expected before arrival. I have proposed a new model; "The Adjustment Process Relation Model", that includes important factors to consider during the adjustment process. The model is based on my own experiences when working at NTNU, Q2S1 and supported by the literature. Analysis on four international PhD candidates is used to show the applicability of the model. The model can be used to raise the awareness of interaction when working among international employees.
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Hardegger, Daniel. "PhD candidates at the University of Berlin and at Columbia University, New York, from 1871 to 1913." Thesis, London School of Economics and Political Science (University of London), 2018. http://etheses.lse.ac.uk/3725/.
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This thesis describes and analyses the PhD candidates in the Humanities at the Friedrich-Wilhelms-Universität zu Berlin and at Columbia University, New York, from 1871 to 1913 as well as the reforms related to the PhD programs at said institutions. The thesis uses primary sources such as the theses and curriculum vitaes of the PhD candidates but also the reports of the universities, statistics released, census records of government institutions as well as newspapers and biographical collections. The goal is to compare the PhD candidates at these two universities according to their numbers, age, gender, religion, place of birth and social background. It further includes a comparison of the reforms and transformation of the two universities with a focus on those which most affected PhD candidates. Instead of focusing on the careers of PhD candidates after they acquired their degree (as in most other studies), this thesis focuses on the background and the life of PhD candidates before they received their degree from their university. By doing so, this thesis will contribute to the understanding of the development of the universities and societies in the late 19th and early 20th centuries, taking into account the debates regarding the German Sonderweg, the professionalisation of education and cross-border exchange among academics wherever possible.
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Evans, Matthew Darold. "Drug candidate discovery by high-throughput virtual screening of protein binding sites /." Diss., Digital Dissertations Database. Restricted to UC campuses, 2006. http://uclibs.org/PID/11984.
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Farahani, Poupak. "Identification of novel candidate obesity genes in hepatic lipase knockout BSB mice /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2003. http://uclibs.org/PID/11984.
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Simpson, Louise. "Epigenetics and breast cancer : a candidate gene association study." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=225333.
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Sognstrup, Larsen Uffe. "New methods for simple and selective tritium labelling of drug candidates & synthetic studies towards crisamicin A /." Cph. : Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences : Department of Isotope Chemistry, Novo Nordisk A/S, 2005. http://www.dfh.dk/phd/defences/UffeSognstrupLarsen.htm.
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Mehrotra, Pankaj. "Immunological and morphological characterization of Candida albicans and Candida haemulonii." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=210107.
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During the infection process Candida albicans has to respond to various stresses imposed by host environment including oxidative and osmolarity stress generated by phagocytic cells such as macrophages and neutrophils. Exposure to caspofungin and other antifungal antibiotics also imposes stress on the C. albicans cell wall. These various stress responses are orchestrated through the activation of multiple stress pathways including the cAMP-PKA, several MAPK pathways and the Ca2+-calcineurin pathway which influence cell wall shape and composition. Such changes were predicted to influence recognition of C. albicans by innate immune cells. During my Ph.D. studies I primarily investigated the effect of the activation or inhibition of these pathways on the interaction with the innate immune cells by examining phagocytosis, the cytokine profile induced by mononuclear and polynuclear cells of the innate immune system. I found that the activation and inhibition of these pathways plays an important role in remodeling of cell wall and hence the immunological profile. Inactivation of cAMP, Calcium signaling pathway by the deletion of TPK1 and CNA1 resulted in marked reduction in pro-inflammatory cytokine production. Inactivation of MAPK pathway by deletion of HOG1 altered major pro-inflammatory cytokine secretion. Cytokine production was also affected by exposure of C. albicans signaling mutants to Calcofluor White, caspofungin, oxidative and osmotic inducing stresses. Cytokine stimulation was also affected by deletion of URA3, exposure of C. albicans to rifmapicin and antimycin A. These results suggest that stress signaling pathways act to regulate collateral changes in the cell wall, which in turn affects the immune reactivity. Pro and anti-inflammatory cytokine and antifungal profiles of Candida haemulonii was also found to be highly variable. Thus regulation and exposure to different microenvironments significantly modifies immunological signature of fungal cells, suggesting that responses to local stresses make the fungal cell surface a moving target for immunological surveillance.
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Matula, Katarzyna Monika. "Evaluation of chemoresistance in oesophagogastric cancers : identification of candidate novel therapeutic targets." Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=201696.
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Development of resistance is the major hindrance to successful chemotherapy treatment in oesophago-gastric (OEG) cancers. Platinum based chemotherapy prolong the survival however only 20 - 30 % of patients survive 5- years since diagnosis of the disease. Therefore understanding of the mechanisms that underlie this phenomenon and identification of novel biomarkers/targets that could predict the response to the treatment and sensitize these tumours to current therapy is needed. We established a panel of human cancer cell lines of oesophagus (OE21 and OE33) and gastric cardia (AGS) resistant to oxaliplatin, cisplatin and docetaxel. To study mechanisms of drug resistance we performed gene expression profiling on resistant and parental lines and differentially expressed genes involved in sphingolipids / lysosomes metabolism have been shown as associated with drug resistance. Selected markers were validated on mRNA and protein levels among the panel of OEG cell lines and clinical specimens. Cellular levels of sphingolipid species were determined in drug sensitive and resistant lines using mass spectrometry. This study revealed a positive correlation between over-expression of sphingosine kinase 1 (SPHK1) and increased levels of sphingosine -1-phosphate (S1P) associated with drug resistance in gastric cancer cell lines. Moreover it showed the predictive value of SPHK1 as high level of this protein correlates with poor survival of OEG cancer patients treated with cisplatin based chemotherapy, in contrast to those patients that received surgery alone. Additionally, lipidomic profiling data showed possibly distinct mechanisms of drug resistance between gastric and oesophageal tumours, indicating that mechanisms of drug resistance are likely cell type, rather than drug specific. In conclusions, this study proofs the clinical relevance of our in vitro experimental models to study mechanisms of drug resistance in OEG tumours and provides the source of novel biomarkers for targeted therapy strategies in this disease.
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Abubakar, Zainab Adamu. "Aquaporins as candidate genes for drought avoidance QTL on rice chromosome 7." Thesis, University of Aberdeen, 2015. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=228563.
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De, La Torre Guadalupe Xavier. "Selection from a social distance theory perspective : superintendents' perceptions of equally qualified candidates /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2003. http://uclibs.org/PID/11984.
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Thesis (Ph. D.)--Joint Doctoral Program in Educational Leadership (California State University, Fresno and University of California, Davis).<br>Typescript. Includes bibliographical references. Also available via the World Wide Web. (Restricted to UC campuses).
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Yue, Yujuan. "Characterization of potential rhesus cytomegalovirus vaccine candidates : glycoprotein B and phosphoprotein 65-2 /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2004. http://uclibs.org/PID/11984.
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Pasdar, Alireza. "Genetics of stroke : a study of phenotyping and identifying candidate genes for ischaemic stroke." Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=185655.
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Stroke is the leading cause of disability and the third leading cause of death in the UK. Ischaemic stroke is the commonest form of stroke and has a highly complex risk factor profile and phenotype making it difficult to unravel the genetic background. For the purpose of clinical or genetic studies, being able to correct for stroke subtype in the analysis strengthens the validity and generalisability of outcomes. Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria for classification of stroke patients have been used and validated in this study. Disordered lipid metabolism may predispose to stroke or stroke subtypes. This thesis investigates important polymorphisms of genes involved in lipid metabolism such as PONs (PON1, 2 and 3) and ABCA1, and their relationships with lipid profile and with stroke in our control and ischaemic stroke populations. Data shows that although individual variations of PON genes (PON1-Q192R, PON1-L55M, PON2-C311S, PON2-A148G and PON3 SNPs) do not have any significant effect on ischaemic stroke, combination of these SNPs (haplotypes) may infer some degree of protection or risk of ischaemic stroke. Variations in ABCA1 gene including R219K can also influence the lipid profile. Furthermore, analysis of the effect of FLAP gene polymorphisms, taking into account possible confounders, suggests a role for HapA in stroke caused by large vessel disease (LVD). We then address DNA pooling as a method for global genotyping and report the results of screening SNPs of further genes involved in lipid metabolism and vascular rheology including CETP, LCAT and Cx37 (GJA4). This study suggests a role for Cx37 gene in our ischaemic stroke population. In conclusion, while some associations have been found, further work should concentrate on very large well phenotyped cohorts in order to further dissect the role of genetics in predisposing to ischaemic stroke.
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Langham, James J. "Discovering drug candidates in virtual chemical libraries : a novel graph-based method for virtual screening /." Diss., Digital Dissertations Database. Restricted to UC campuses, 2006. http://uclibs.org/PID/11984.
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O'Donnell, Raymond William. "Chitinolytic enzymes of Candida albicans." Thesis, University of Aberdeen, 1991. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=158392.
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It has been envisaged that lytic enzymes may be crucial in determining the morphology and growth of fungi, and may therefore represent a target for antifungal agents. The chitinolytic system of <i>Candida albicans</i> was investigated using a range of 4-methylumbelliferyl glycosides as model substrates, and its potential as a target for antibiotics has been assessed. Maximum hydrolysis was obtained with substrates having monomer and tetramer chain lengths, being attributed to <i>N</i>-acetylglucosaminidase and endochitinase respectively. Activities were investigated in cell fractions, vacuoles, and also in whole cell preparations. The characteristics of both chitinase and <i>N</i>-acetylglucosaminidase were examined, including pH and temperature optima and Km values. Chitinase was semi-purified on Fast Protein Liquid chromatography system and activity could be located after native polyacrylamide gel electrophoresis. Analysis of chitinase activity during the growth of the yeast morphology of <i>C.albicans</i> revealed maximal activities during the logarithmic phase, suggesting a relationship of chitinase levels to active growth of the pathogen. It was found that the antibiotic allosamidin was a potent inhibitor of chitinase activity of <i>C.albicans</i>, but not of <i>N</i>-acetylglucosaminidase. Conversely, an analogue of <i>N</i>-acetylglucosamine was found to be a potent inhibitor of <i>N</i>-acetylglucosaminidase but not of chitinase. Treatment of yeast suspensions with allosamidin resulted in an increased chain length. No cell death, or discernible pattern of change in the radiolabelling was observed in the presence of either allosamidin or <i>N</i>-acetylglucosamine analogue. Similarly no consistent change in the optical density of cultures was observed in the presence of either inhibitor. Even in the presence of the membrane permeabilising agent amphotericin no effects were observed above those achieved with amphotericin alone. Comparative studies were carried out upon the chitinolytic activity of <i>Kluyveromyces lactis</i> toxin and bovine serum. The chitin synthetic system of <i>Benjaminiella poitrasii</i> was compared to that of <i>C.albicans</i>.
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Heinz, Werner J. "Identifikation und Charakterisierung von PHR3, einem zu der PHR-GAS-Familie homologen Gen bei Candida albicans." Doctoral thesis, [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=964401614.
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Sartini, Becky Lynn. "Characterization of boar sperm plasma membrane candidate oocyte membrane fusion proteins and investigation of oocyte membrane binding sites in boar sperm populations /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2002. http://uclibs.org/PID/11984.
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Thomson, Darren David. "The exploratory behaviour of Candida albicans hyphae." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=206607.
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Cells that grow by apical extension, such as neurons, pollen tubes, root hairs and fungal hyphae, orient their growth in response to tip contact with physical cues in the environment (thigmotropism). I use Candida albicans, an opportunistic human fungal pathogen, as a model to assess tip re-orientation growth responses after contact. Thigmotropism is associated with virulence (Brand et al., 2008), therefore this thesis aims to characterise the responses that C. albicans displays after contact events in an enclosed chamber featuring various obstacles and shapes. It was found that hyphae grow along surfaces in a nose-down manner, presumably to identify and exploit gaps in the substrate. Further, hyphae preferentially grow nose-down on softer surfaces when given the option of two contrasting surfaces, implying novel substrate sensing mechanisms. Contact-dependent hyphal responses are outlined, where perpendicular contact with an obstacle induced various growth responses after re-orientation. Further, important cytoskeletal regulators of thigmotropism were identified, which subsequently regulate substrate indentations. The applied force generated by hyphal tips was quantified, which was enough to penetrate mammalian membranes without the need of hydrolytic enzymes, and this was modulated by a change in environmental carbon source. This thesis describes several new exploratory behaviours in C. albicans, which may apply to hyphae in general, since behaviours described here have also been observed in other filamentous fungi. Further, the role of septins as regulators of directional growth is discussed. The first chapter describes contact-dependent behaviours that support the ability of hyphae to be opportunistic and exploit their topographical environment to invade surfaces. The second chapter presents a detailed description of how the fungus responds to perpendicular contact events. Finally, the third chapter identifies cytoskeletal regulators important for thigmotropism. Together, this thesis brings together multiple aspects of cell biology and biophysics that apply during polarised tip growth, which adds knowledge to the narrative of why hyphae are such successful space invaders.
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Rumaiz, Abdul K. "Cobalt doped titanium dioxide, a possible candidate for dilute magnetic semiconductor." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 149 p, 2008. http://proquest.umi.com/pqdweb?did=1459915881&sid=3&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Rohr, Lia. "Candidate sex and preferred issue agendas : the gendering of campaign websites /." Available to subscribers only, 2008. http://proquest.umi.com/pqdweb?did=1594498581&sid=12&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Stewart, Ashley Estelle. "The Lived Experiences of Black Doctoral Students: Institutional Racism and Race-Based Traumatic Stress." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1546541858892271.
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Sandai, Doblin Anak. "The regulation of carbon assimilation in Candida albicans." Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=203832.
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The main objective of this thesis was to study the effects of glucose on the regulation central carbon metabolic functions in the human fungal pathogen Candida albicans (C. albicans). The virulence of C. albicans is dependent upon fitness attributes as well as virulence factors. These attributes include robust stress responses and metabolic flexibility (Brown, 2005). The assimilation of carbon sources is fundamentally important for growth in all organisms and essential for the establishment of infections by pathogens, such as C. albicans in their human host. The C. albicans PCK1 and ICL1 genes, which encode the gluconeogenic and glyoxylate cycle enzymes phosphoenolpyruvate carboxykinase and isocitrate lyase are required for growth on non-fermentable carbon sources such as lactate and oleic acid. This thesis examines the impact of glucose upon the assimilation of secondary carbon sources such as lactate and oleic acid by C. albicans. The addition of 2% glucose repressed the CaPCK1 and CaICL1 genes. However, the enzymes CaIcl1 and CaPck1 were not destabilised by glucose and they retained at high levels following glucose addition. As a result, C. albicans cells continued to assimilate lactate and oleic acid in the presence of glucose. In contrast, the ScPck1 and ScIcl1 proteins were degraded rapidly in S. cerevisiae, and lactate and oleic acid assimilation was repressed in response to glucose. Therefore, while C. albicans and S. cerevisiae display similar responses to glucose at the transcriptional level, their responses at post-transcriptional and metabolic level diverge significantly. As a result, C. albicans can assimilate both glucose and alternative carbon sources at the same time. Next, the molecular apparatus that triggers the destabilisation of target proteins in response to glucose in C. albicans was studied. The expression of C. albicans the ICLI ORF in S. cerevisiae suggested that CaIcl1 has lost the molecular signal that triggers destabilisation in response to glucose, as CaIcl1 was not degraded in response to glucose in S. cerevisiae. However, when ScIcl1 was expressed in C. albicans ScIcl1 was rapidly degraded in response to glucose indicating that C. albicans has retained the molecular apparatus for glucose-accelerated degradation of target proteins. ScIcl1 degradation was slowed in C. albicans ubi4/ubi4 mutants. Furthermore, the addition of a putative of S. cerevisiae ubiquitination site carboxy terminus of CaIcl1 led to glucose-accelerated degradation of this protein in C. albicans cells. Therefore, glucose triggers accelerated degradation of target proteins in C. albicans via a ubiquitin-dependent process.
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McKenzie, Christopher Gordon Jemison. "Candida albicans recognition by and escape from macrophages." Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=167784.
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Disruption of <i>N-</i>mannosylation and <i>O</i>-mannosylation on the <i>C. albicans</i> outer cell wall increased the rate by which <i>C. albicans</i> is ingested by macrophages. Conversely, disruption of phosphomannosylation reduced the rate of <i>C. albicans</i> is phagocytosis. Alterations to the outer cell wall and genetic or chemical inhibition of hyphal morphogenesis in <i>C. albicans</i> resulted in significantly abrogated macrophage killing <i>in vitro</i>. Disruption of <i>C. albicans </i>ability to tolerate oxidative stresses also perturbed its ability to escape from and kill macrophages. The engagement of specific receptors on the macrophage surface is an essential component of <i>C. albicans</i> recognition and clearance. In the presence of serum, blocking pattern recognition receptors associated with specific fungal cell wall epitopes (Mannose Receptor, Dectin 1 and CD16/32) resulted in an initial decrease in phagocytosis and decreased macrophage killing. Blocking macrophage pattern recognition receptors using soluble components of the<i> C. albicans</i> cell wall resulted in decreased phagocytosis under serum free conditions of <i>O-</i>linked mannans only, and reduced macrophage killing for macrophages pre-exposed to <i>N-</i>mannan and laminarin. The presence of serum increased the rate of uptake for macrophages pre-exposed to <i>N-</i>mannan and laminarin, and had no affect upon macrophage killing. The interaction of <i>C. albicans</i> cell wall epitopes with macrophage pattern recognition receptors, coupled with <i>C. albicans</i> ability to respond to stresses encountered after ingestion are critical determinants of the macrophage’s ability to ingest and process <i>C. albicans.</i>
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Tilliman, Anna Theresa. "Nitrosative and combinatorial stress responses in Candida albicans." Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=192303.
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Fungal nitrosative stress responses are understudied and poorly understood. Also, while the responses of the pathogen Candida albicans to individual oxidative and cationic stresses have been characterised relatively well, the responses of this pathogen to simultaneous combinations of these and nitrosative stresses have not been elaborated. Yet, C. albicans is exposed to these combinatorial stresses during disease progression. Therefore, the overall aim of this project was to characterise the "Nitrosative and Combinatorial Stress Responses in Candida albicans". The first objective was to elucidate nitrosative stress response mechanisms in C. albicans at a cellular, transcriptional and post-translational level. Genetic screens revealed that the Hog1 and Mkc1 signalling pathways contribute to nitrosative stress adaptation in addition to Cta4 signalling. The next objective was to characterise responses to combinatorial nitrosative, oxidative and/or cationic stresses with respect to the relevant signal transduction pathways. Unexpectedly, combinatorial stresses did not activate classical nitrosative (Cta4) and oxidative (Cap1) signalling mechanisms. Instead, Hog1 signalling was found to play a significant role in the combinatorial stress adaptation. Dramatic changes in the GSH redox potential were observed in response to both single and combinatorial stresses. Thus, GSH redox regulatory mechanisms were explored in more detail. BLAST searches of the C. albicans genome were performed, revealing genes encoding a putative NADPH-dependent glutathione reductase (Glr1) and a GSH-dependent S-nitrosoglutathione reductase (Fdh3). We confirmed that both conserved enzymes are involved in the maintenance of redox homeostasis and hence are crucial for C. albicans adaptation during host-pathogen interactions. This was achieved by showing that inactivation of Glr1 or Fdh3 disturbs GSH redox homeostasis, confers oxidative and formaldehyde stress sensitivity and attenuates virulence.
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Mukaremera, Liliane. "Morphogenesis in Candida albicans : shaping the cytokine signature." Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=202132.
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Leach, Michelle D. "Impact of post-translational modifications during stress adaptation in Candida albicans." Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=167804.
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Organisms exist in complex and dynamic environments. Facing numerous challenges, microorganisms must continuously monitor environmental changes and adapt to these if they are to survive. For example, the major fungal pathogen of humans, Candida albicans experiences diverse stresses, including temperature fluctuations, oxidative stress and enzymic processes, that cause molecular damage. Post-translational modifications such as phosphorylation play major roles in stress adaptation, for example through activation of MAP kinase pathways and transcription factors such as the heat shock transcription factor, Hsf1. However, other post-translational modifications such as ubiquitination and sumoylation have been relatively understudied. Nevertheless, they are believed to play crucial regulatory roles in many cellular processes including stress adaptation. Therefore, in this study the roles of ubiquitin and SUMO (small ubiquitin-like modifier) have been investigated in C. albicans. Proteomics was used to identify ubiquitination and sumoylation targets, and this was combined with molecular analyses of the UBI4 and SMT3 genes, which encode polyubiquitin and SUMO, respectively. Both ubiquitination and sumoylation were shown to play important roles in morphogenesis, cell division and stress adaptation in C. albicans, including adaptation to heat and oxidative stresses. In addition, the dynamics of heat shock adaptation were examined in C. albicans using a systems biology approach. Hsf1 is known to activate HSP90. In this study, Hsf1 was found to be transiently phosphorylated in response to heat shock, and Hsp90 was found to down-regulate this Hsf1 phosphorylation. This led to the identification of an autoregulatory loop that controls thermal adaptation in C. albicans. A mathematical model of heat shock regulation (constructed in collaboration with Katarzyna Tyc and Edda Klipp) provided novel insights into the regulation of this evolutionarily conserved environmental response and the significance of thermal adaptation during systemic Candida infection.
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Nather, Kerstin. "Dynamics and heterogeneity of Candida albicans cell surface proteins." Thesis, University of Aberdeen, 2010. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=158587.
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Candida albicans is the major fungal pathogen of humans and its cell surface mannoproteins play important roles in adhesion, interactions with the host and signal transduction. Most of the covalently attached mannoproteins are linked to the cell surface by glycosylphosphatidylinositol (GPI) anchors. Over 100 putative GPI-proteins have been identified in silico in the C. albicans genome, yet the majority remain uncharacterised with regards to their function and regulation. This study uses different approaches to define the role and regulation of selected GPI-protein genes. Expression analyses demonstrated transcriptional regulation of these genes in response to membrane and wall stresses including antifungal drugs. We propose that these genes encode proteins with important roles in cell wall remodelling. One protein, Pga54 was selected for further analysis. Null mutant and reintegrant strains were constructed and phenotypically analysed. The mutant phenotype was for the greatest parts inconclusive, but it showed a minor virulence defect in a mouse model of systemic infection. Using a tagged version of Pga54 the protein could be detected in the GPI fraction of the cell wall in wild type C. albicans cells and was shown to be higher expressed in cells subjected to stress. To establish whether they play a role in adhesion to host cells selected uncharacterised GPI proteins were heterologously expressed in the non-adherent yeast Saccharomyces cerevisiae. The newly generated S. cerevisiae strains did not show any differences in adhesion to human buccal epithelial cells. Further, the examination of tandem repeat variation in genes encoding GPI anchored proteins in different C. albicans strains indicates that this is could be a further means of creating diversity and heterogeneity at the cell surface. This study employs different methods to study the role and the dynamics of cell surface proteins. In future studies these approaches could be applied to all identified GPI proteins to obtain a comprehensive picture of cell surface diversity in Candida albicans.
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Moorhouse, Alexander James. "Population structure of Candida species : spatio-temporal distribution of strain types and association with ancient Hominins." Thesis, University of Aberdeen, 2016. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=229378.
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Cruz, e. Almeida Mariana. "The role and regulation of Pxl1 in the hyphal steering of Candida albicans." Thesis, University of Aberdeen, 2017. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=232370.
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Ene, Iuliana V. "Impact of host carbon sources in the pathobiology of Candida albicans." Thesis, University of Aberdeen, 2012. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=189402.
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Candida albicans is the most common systemic fungal pathogen of humans. Virulence factors, fitness attributes and the host immunity ultimately determine the ability of C. albicans to reside as a commensal organism or an opportunistic pathogen in its human host. C. albicans displays a high level of flexibility in adapting to and infecting diverse niches in its human host. Generally occupying glucose-poor niches, C. albicans often depends upon alternative carbon sources to grow and establish infections. However, most cellular and molecular investigations of this pathogen have been performed on glucose-grown cells, and the relationship between physiological nutrients and drug resistance or virulence has not been studied. The main objective of this thesis was to study the effects of host carbon sources upon C. albicans cell biology and how this in turn affects the stress and drug resistance, immune recognition and virulence of this fungus. Growth on this physiologically relevant alternative carbon source was shown to influence the cell wall architecture of C. albicans and alter its resistance to a variety of stresses and antifungal drugs. Differences in stress resistance were less dependent on the key stress signalling pathways than on major architectural changes in the C. albicans cell wall that influenced its biochemical and biophysical properties. It was also shown that carbon source has a major impact upon C. albicans pathogenicity, altering cell adhesion and host virulence, in both systemic and vaginal infections. Considering the different niches that Candida can colonise in the body, these findings have the potential to change our views about the interactions that occur between the fungus and its human host. Taken together, the results of this project demonstrate that differential nutrient availability within diverse host niches influences the ability of pathogenic Candida species to counteract local chemical insults and pharmacological interventions.
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Bohovych, Iryna M. "Impact of glucose on oxidative stress resistance in Candida albicans." Thesis, University of Aberdeen, 2012. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=186766.
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Candida albicans, a successful human pathogen, displays the phenomenon of glucoseenhanced oxidative stress resistance (Rodaki et al., 2009), which is not observed in other yeast species tested. The molecular bases of the phenomenon are not clear. It was suggested that glucose signalling might play a major role. Therefore, the impact of specific C. albicans mutations was tested to determine which of three known major glucose signalling pathways are required for glucose-enhanced oxidative stress resistance. Two major glucose signalling pathways were found to contribute to the phenomenon (the glucose repression pathway and the cAMP pathway), and a third pathway (the SRR pathway) is not essential for this response. The next step was to identify targets of these pathways that might contribute to the phenotype. First, it was tested whether known oxidative stress systems contribute to the GEXSR. The selected targets represented almost all main systems involved in redox control and ROS detoxification (catalase, superoxide dismutases, thiredoxins, and glutathione peroxidases) which seemed to contribute not significantly to the GEXSR. The exceptions to this were glutathione reductase (Glr1) and glutaredoxin (Grx2/Ttr1), inactivation of which affected manifestation of the phenomenon. This reinforced the view that the GSH/GSSG balance plays a key role in the GEXSR. Second, comparative analyses of transcriptomic profiles of C. albicans glucose- and lactategrown cells in response to oxidative stress and glucose treatment correspondingly revealed a small set of commonly up-regulated genes: UCF1, RNR22, MOH1, orf19.3302, and HSP21/orf19.822 (Enjalbert et al., 2006; Rodaki et al., 2009). Each potential GEXSR-specific gene appeared to be regulated in a distinct manner by the major glucose signalling pathways. The ectopic expression of potential GEXSR targets did not provide any experimental evidence to support their roles in this response. That might be related to inefficient expression from ACT1 promoter under the experimental conditions tested, and also caused by other effects.
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Walker, Louise. "Dynamic responses of the fungal cell wall to stress and antifungal treatment." Thesis, University of Aberdeen, 2010. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=136783.
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The main aim of this project was to determine the potential of increased chitin content as a mechanism of resistance to caspofungin in different fungal pathogens. <i>C. albicans</i> wild-type cells were pre-grown with a combination of CaCl<sub>2</sub> and CFW prior to caspofungin treatment. This result sin a three-fold increase in cell wall chitin. Wild-type cells, which had elevated chitin content, were less susceptible to caspofungin. Priming cells to activated chitin synthesis was also able to compensate for the loss of the normally essential <i>CaCHS1</i>, through formation of three novel forms of salvage septa. In the absence of both <i>Ca</i>Chs1 and <i>Ca</i>Chs3, which are typically involved in septum formation, the class I chitin synthases, <i>Ca</i>Chs2 and <i>Ca</i>Chs8, could be stimulated to synthesise a proximally offset salvage septum. When <i>Ca</i>Chs3 was the only remaining chitin synthase, treatment with CaCl<sub>2</sub> and CFW, led to the formation of thick chitin-rich salvage septa. <i>Ca</i>Chs2<i> </i>and <i>Ca</i>Chs3 could be stimulated by treatment with CaCl<sub>2</sub> and CFW to synthesise a thin salvage septum similar to the septum of wild-type cells. All three salvage septa were capable of restoring viability and cell division in <i>C. albicans.</i> The compensatory increase in chitin content in response to caspofungin treatment was not specific to <i>C. albicans</i> because clinical isolates of <i>C. tropicalis, C. parapsilosis </i>and <i>C. guilliermondii</i> and the filamentous fungus, <i>A. fumigatus</i>, also demonstrated an increase in chitin content after treatment with caspofungin. Isolates of <i>C. glabrata</i> and <i>C. krusei</i> showed no change in chitin content when exposed to caspofungin. The results of this thesis highlight the potential for using chitin synthase inhibitors in combination therapy with the echinocandins.
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Sood, Prashant. "Tools to study the transition from fungal commensalism to systemic infection." Thesis, University of Aberdeen, 2019. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=240695.
Full textAbstract:
Candida albicans colonizes the gastrointestinal tract of up to 75 % healthy individuals. It usually cohabits the gut as an innocuous commensal. But in critically ill patients whose gut barrier, immune system and normal gut microbiota are compromised, C. albicans often transmigrates the gut barrier, transforms into an invasive pathogen and causes fatal systemic infections. The genetic transitions that drive this transformation in C. albicans have been a major focus of research and have led to the identification of key transcription factors that regulate this commensal-to-pathogen transition. However, the current challenge lies in identifying the downstream pathways and effectors that bring this transition into effect. This thesis addressed this challenge by developing 11 new bioinformatics tools, including 6 comprehensive databases, 4 novel software packages and 1 analysis framework. These databases included a comprehensive topological map of the mammalian gut biogeography, a C. albicans microarray database comprising of 3,091 publically available microarray transcript profiles, C. albicans RNA-seq gene expression and small variant databases extracted from 1,177 publically available RNA-seq samples, a C. albicans gene alias database comprising of 113,297 gene aliases representing the 6,735 open reading frames of C. albicans, and a C. albicans gene ontology slim comprising of 1,194 C. albicans-specific gene ontology terms. These databases were accompanied by a robust analysis framework which brought together these resources for quality control, batch correction and weighted gene co-expression network analysis. All these tools were finally employed in a pilot exploration of the C. albicans gut commensal-to-pathogen transition, which demonstrated the effectiveness of these bioinformatics resources. The analysis unveiled known regulators, uncharacterized gene networks, pathways and effectors potentially crucial for the C. albicans gut commensal-topathogen transition. These resources are a step towards a better understanding of this transition and can also be utilized for examining various other aspects of C. albicans biology.
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Preechasuth, Kanya. "Regulation and cell biology of chitin synthesis in Candida albicans." Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=202781.
Full textAbstract:
Chitin biosynthesis in the fungal cell wall is essential for cell viability. Chitin play roles in maintaining cellular integrity and up regulation of chitin synthesis helps protect the cell from cell wall stresses or cell wall damaging antifungal agents such as caspofungin. In Candida albicans chitin is synthesised by four chitin synthases (Chs), Chs1, Chs2, Chs3, and Chs8. The biological function of Chs2 and Chs8 (class I chitin synthases) is less well understood. The major objective of this thesis was to understand the biological function of the class I chitin synthases. Chs2-YFP and Chs8-YFP showed a dynamic localisation at septation sites, which were first visualised as a bar which then contracted to a spot. This spot then separated into two spots, one on each sides of the septum. These two spots remained there until yeast cell separation, and remained at this location throughout several subsequent hyphal cell cycles. Chs2-YFP also localised to hyphal tips. The phenotype of a chs2Δchs8Δ double mutant was re-investigated using the propidium iodide. Intact dead germ tubes and hyphal tip lysis was observed in a chs2Δchs8Δ mutant cells. This suggested that Chs2 and Chs8 play a major role in the maintenance of hyphal tip integrity and polarised growth and perhaps a minor role in septum formation. Studies were also performed to assess whether phosphorylation regulated the localisation of Chs2-YFP. It was shown that the localisation of Chs2-YFP to septation sites was regulated by phosphorylation on S222. A version of Chs2-YFP that could not be phosphorylated (Chs2S222A-YFP) localised at the septa in lower amounts than the Chs2-YFP, and a version of Chs2-YFP that mimicked constitutive phosphorylation (Chs2S222E-YFP) localised normally. This suggested that phosphorylation of Chs2 on S222 facilitates the localisation of Chs2-YFP at septation sites, and that dephosphorylation is not required for this cellular localisation. In the presence of cell wall stresses (CaCl2/CFW) and caspofungin, more Chs2-YFP was observed and the average intensity of fluorescence of Chs2-YFP was higher in the presence of these stresses than in untreated cells.
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Rudkin, Fiona. "Isolation and functional characterisation of human anti-Candida antibodies for fungal immunodiagnostics and immunotherapy." Thesis, University of Aberdeen, 2015. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=227986.
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Andronico, Luca Alfio <1990>. "Investigation of the Thermochemiluminescent (TCL) phenomenon as innovative detection technique for (bio)analytical applications: from the synthesis of new TCL candidates to the realization of TCL-based probes for immunoassays." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2018. http://amsdottorato.unibo.it/8530/1/PhD%20thesis_Luca%20Alfio%20Andronico.pdf.
Full textAbstract:
In the present PhD thesis, thermochemiluminescence (TCL) phenomenum as a new
promising tool for development of innovative (bio)analytical detection methods has been
investigated. The first part of this work was focused on the synthesis of new TCL
candidates, aiming the optimization of the TCL properties in terms of lower decomposition temperatures and higher fluorescence quantum yields of
the generated excited fragments. Moreover, through a chemometric
approach, both the structural and electronic molecular descriptors for each molecule
were analysed and used to elaborate a model able to predict the olefin photooxygenation
outcome. Moving forward, the focus was shifted to the realization of TCL-based nanosensors for immunoassay applications. In particular, the fabrication of both molecular and nanometric-scale probes was performed, linking the TCL substrate (1,2-dioxetane) directly to universal biomarker
or encapsulating it within a polymeric nanoshell. Concerning the molecular probe, acridin 1,2-dioxetane was functionalized with biotin in order to create a TCL sensor for detection of streptavidin-based targets. TCL process was, then, combined with the semiconductive polymer dots (Pdots) technology to realize ultrabright thermo-responsive nanoparticles able to detect biotinylated compounds of interest. In particular, the FRET mechanism occurring between the polymeric matrix of Pdots and TCL substrate has been exploited to both enhance the light generation and shift the emission towards longer wavelengths. Furthermore, TCL-Pdots were tested in a noncompetitive sandwich-type immunoassay for detection of Immunoglobuline G (IgG). The last part of this work was focused on the realization of a home-made portable device to combine TCL-based detection technique with smartphone technology. All the different items constituting the apparatus have been fabricated exploiting a 3D printing process and acrylonitrile-butadiene-styrene (ABS), as starting material. The device was tailored to the camera of a Nokia Lumia 1020 exploiting, thus, the performance of the complementary Metal Oxide
Semiconductor sensor of the smartphone’s camera.
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Bedekovic, Tina. "Regulation of the Rsr1 GTPase during polarized growth in Candida albicans." Thesis, University of Aberdeen, 2018. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=235973.
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Lee, Keunsook Kathy. "Echinocandin resistance of Candida albicans due to elevated cell wall chitin." Thesis, University of Aberdeen, 2012. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=210190.
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Whibley, Natasha. "The role of effector and regulatory helper T cells in a murine model of systemic Candida albicans infection." Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=192231.
Full textAbstract:
Diseases caused by fungi are increasing worldwide and are often associated with high mortality rates. In particular, the normally harmless commensal Candida albicans can cause serious disease if immunological and physiological barriers are perturbed, leading to systemic infection, which is fatal in up to 45% of cases. The adaptive immune response is believed to be important in protection against systemic candidiasis, however, the roles of different helper T (Th) cell subsets, particularly Foxp3+ regulatory T (Treg) cells, remain largely unexplored. The aims of this study were to adapt a mouse model of systemic C. albicans infection to test whether the numbers of Th1, Th2, Th17 and Foxp3+ Treg cells increase in mice with systemic C. albicans infection, and determine their contribution to disease. C. albicans drove the expansion of Th1, Th2 and Th17 cells, as well as multiple Foxp3+ populations that displayed characteristics of natural Treg, induced Treg, Th17 and Th1 cells in vitro and in vivo. The expanded Foxp3+ T cells inhibited Th1 and Th2, but promoted Th17, responses to C. albicans antigens in vitro and exacerbated disease, since their depletion in vivo reduced kidney fungal burden and inflammatory lesions. Furthermore, systemic infection with a weakly virulent C. albicans strain was associated with reduced Treg responses compared to those induced during lethal systemic infection. These data lead to a model for systemic candidiasis whereby Treg expansion promotes Th17 responses that drive pathology, and have implications for future immunotherapy.
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Okai, Blessing. "The role of Rab14 in the maturation of macrophage phagosomes containing Candida albicans." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=214847.
Full textAbstract:
The virulence of the opportunistic fungal pathogen Candida albicans is in part due to its ability to switch between a yeast and hyphal form; permitting physical rupture and escape from macrophages after phagocytosis. This interesting feature makes C. albicans a good model organism to study in the context of phagosome maturation and in particular, the role of the small GTPase Rab14 in this process. Rab14 is recruited to bacterial phagosomes containing Chlamydia trachomatis (Capmany & Damiani, 2010) and Mycobacterium bovis BCG (Kyei et al, 2006) and aids their survival in macrophages but its role in phagosomes containing fungal pathogens is not known. Here, an important role for Rab14 in protecting macrophages against hyphal mediated lysis by C. albicans is demonstrated. Macrophages were transfected to express eGFP-Rab14, or dominant negative variants (eGFP-Rab14 S25N and eGFP-Rab14N124I); or were transfected with anti-Rab14 siRNA; then infected with live C. albicans and observed using sophisticated live cell imaging and analysis tools. Phagosomes containing live C. albicans became transiently Rab14-positive within 2 minutes following engulfment. Interestingly, a prolonged retention of Rab14 on phagosomes depended on C. albicans morphology. Phagosomes containing hyphal forms retained Rab14 for twice as long as for phagosomes containing the yeast form. Depletion of endogenous Rab14 did not affect macrophage migration towards C. albicans, the rate of engulfment or acquisition of markers of early phagosome maturation to phagosomes containing C. albicans. Furthermore, reduced Rab14 expression did not influence the kinetics of Rab5 localisation to phagosomes in macrophages that were co-transfected. Importantly, partially depleting Rab14 delayed the appearance of late phagosome maturation indicators LAMP1 and activated cathepsin in phagosomes containing live C. albicans.Rab14 knockdown was associated with a significant increase in macrophage killing by C. alibica The data presented in this thesis demonstrate the dynamic relationship between host and pathogen which can be visualised in real time at the level of individual phagosomes. Rab14 plays an important role during phagosome maturation which impacts on the later stages of phagosome maturation and is important for phagocyte survival after phagocytosis of C. albicans.
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Drummond, Rebcca Anne. "The role of C-type lectin receptors in Candida albicans specific immunity." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=211412.
Full textAbstract:
Candida albicans is a human fungal pathogen responsible for superficial mucosal infections and life-threatening systemic disease. Despite the availability of potent antifungal drugs, mortality rates of systemic candidiasis remain high. Alternative therapies and vaccines are therefore desirable; however their generation depends on a comprehensive understanding of antifungal immunity. Innate recognition of fungi by the immune system is primarily mediated by a class of myeloid-expressed molecules termed the C-type lectin receptors (CLRs). CLRs mediate a variety of functions including phagocytosis, fungal killing, initiation of inflammation, and the generation of adaptive immunity. Adaptive responses are required for long-term memory and are shaped by the initial innate immune response controlled by CLR-expressing myeloid cells, yet the influence of CLRs on fungal-specific adaptive immunity is not well understood. In this thesis, the generation of C. albicans-specific T-cell immunity, particularly the CD4+ T-cell response, was investigated using OT.II transgenic T-cells and an ovalbumin-expressing strain of C. albicans. Using this model system, a novel role for the CLR, Dectin-1, was found in controlling CD4+ T-cell viability and recruitment to the GI tract. No roles for Dectin-1, or the related CLR Dectin-2, were found in controlling T-cell responses in the C. albicans infected kidney. However, it was found that, surprisingly, antigen-specific CD4+ T-cells did not migrate into the kidney during infection. Artificial restoration of this defect using immunoliposomes could significantly protect against infection, thus highlighting the importance of these lymphocytes to antifungal immunity. Furthermore, this thesis also explores the generation of better tools to study C. albicans-specific T-cell responses, and the roles of uncharacterised CLRs in the generation of adaptive immunity. Collectively, this research provides new insights into the generation and regulation of antigen-specific CD4+ T-cell immunity during C. albicans infections.
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Lyall, Natalie. "The role of RAB2 in the maturation of macrophage phagosomes containing Candida albicans." Thesis, University of Aberdeen, 2018. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=238253.
Full textAbstract:
Phagosome maturation is a dynamic process involving the engulfment and degradation of pathogens by phagocytic cells. However, several pathogens have employed mechanisms that facilitate their survival and escape from the phagosome. The fungal pathogen, Candida albicans, is capable of switching from yeast to hyphal form to facilitate its pathogenicity and escape from the phagosome. Rab GTPases are key regulators in phagosome maturation by mediating interactions with the endocytic pathway and leading to biogenesis of the phagolysosome. The temporal localisation dynamics of Rab2 on maturing phagosomes containing live C. albicans was investigated. Live-cell imaging revealed green fluorescent protein (GFP)-tagged Rab2 was recruited to C. albicans-containing phagosomes. Rab2 appeared on phagosomes within 2 min following complete engulfment of C. albicans. Rab2 persisted transiently on macrophage phagosomes and this correlated with the length of C. albicans hyphae at the time of uptake, suggesting C. albicans morphology modulates Rab2 localisation dynamics. Expression of dominant negative or dominant active Rab2 did not affect macrophage migration, the rate of engulfment or phagosome acidification during the early stages of phagosome maturation. Furthermore, altered expression of Rab2 did not interfere with C. albicans ability to escape from and kill macrophages, suggesting Rab2 is not involved in the outcome of the host-pathogen interaction. However, altered expression of Rab2 reduced the acquisition of the late-stage phagosome maturation markers, cathepsin B and LAMP1, suggesting Rab2 impacts upon phagosome-lysosome fusion. Finally, the uptake of other particles by macrophages revealed Rab2 recruitment, as well as localisation dynamics on phagosomes, may be cargo-dependent. Through the use of live-cell imaging, real-time dynamics of phagosome biogenesis in live cells was examined, offering unique insight at the host-pathogen interface.
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De, Almeida Nogueira Maria Filomena. "Candida albicans signalling pathways and the regulation of cell wall biosynthesis under stress." Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=203748.
Full textAbstract:
The main aim of this project was to study Candida albicans cell wall biosynthesis in response to stress. The role of the MAPK, Ca2+/calcineurin and cAMP/PKA signal transduction pathways in regulating the C. albicans cell wall stress response was investigated. A library of mutants lacking receptors, signalling elements and transcription factors were screened for alterations in their ability to respond to a range of cell wall stressing agents, including CaCl2, Calcofluor White and caspofungin. Pretreatment of wild-type cells with CaCl2 and CFW, activates the Ca2+/calcineurin and PKC pathways, leading to an increase in chitin content, and reduced susceptibility to caspofungin. Although elevation of cell wall chitin content often resulted in decreased sensitivity to caspofungin, I show here that some strains with increased chitin levels remained sensitive to caspofungin. The results show that elevation of chitin is a common property of a range of mutants that are affected in coordinating cell wall stress pathways, but that multiple mechanisms are likely to operate in maintaining the robustness of the C. albicans cell wall. Some of the mutant strains of the MAPK, Ca2+/calcineurin and cAMP signalling pathways showed evidence of paradoxical growth, whereby less inhibition was achieved by higher concentrations of antifungal drug. The role of chitin-related genes and stress signalling pathways in regulating C. albicans paradoxical growth was also investigated. Based on these results, more detailed analyses were performed to investigate the correlations between sensitivity and resistance to caspofungin, in relation to paradoxical growth. The MAPK-Mkc1 and the calcineurin pathways played major roles in the paradoxical growth effect. There was a proportional relationship between echinocandin concentration and the chitin content of the cell wall although the chitin content did not continue to be upregulated by the highest echinocandin concentration. Different echinocandins, carbon source, cell morphology and medium composition influenced the extent of paradoxical growth effect. The existence of paradoxical growth in resistant strains such as Fks1 also highlights association of paradoxical growth with resistance mechanisms.
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Kastora, Stavroula. "Novel regulators that control the adaptation of a major fungal pathogen to combinations of host signals." Thesis, University of Aberdeen, 2015. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=228983.
Full textAbstract:
One of the major aims of this thesis was to identify novel regulators that drive C. albicans adaptation during growth under different nutrient and temperature conditions. The classical stress response cascades have been previously characterised under standardized, but physiologically irrelevant growth conditions (YPD at 30°C). In this study these pathways and other regulators were examined under more physiologically relevant inputs because metabolic plasticity and thermo-tolerance have been shown to affect stress adaptation (Arguelles et al., 1999; Brown et al., 2014; Cowen, 2009; Diezmann et al., 2014). In this study, we characterized 18.5% of the functional C. albicans ORFeome under 144 different stress conditions by employing a standardized system of robotic screening (Chapter 3). These screens highlighted extensive carbon and temperature-conditional regulators in C. albicans. We identified carbon-conditional contributions of the transcriptional regulators Sfp1 and Rtg3 to stress adaptation in this pathogenic fungus (Chapter 4). Sfp1 was found to regulate the expression of key stress regulators during growth on glucose, whereas Rtg3 induced the expression of these stress genes during growth on lactate. Our screens also revealed a distinct set of transcription factors, Hap43, Swi4, Sfp1, Cap1 and Zcf31, that control regulators of cell wall integrity and that promote antifungal drug resistance in a temperature dependent and yet Hsp90- independent manner. The screens also provided new information about a relatively obscure group of transcriptional regulators in C. albicans; the zinc cluster proteins with focus on Zcf3 and Zcf18 which we further pursued with RNA-sequencing to establish them as modulators of cell cycle, stress resistance and virulence in C. albicans. Lastly, our screens reveal a network of regulators that are homologous to human oncogenes and control fungal growth via modulation of TOR signaling. In conclusion, this thesis has revealed many novel targets for possible antifungal drug development and highlighted the extensive and intricate cross-talk between stress response modules facilitated by physiologically relevant nutrient sources and ambient temperatures.
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Lader, Eric Scott. "Tctex-1 : a candidate gene family for a mouse t-complex distorter (tcd-1) locus /." Access full-text from WCMC, 1989. http://proquest.umi.com/pqdweb?did=744576221&sid=1&Fmt=2&clientId=8424&RQT=309&VName=PQD.
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Bezayiff, Nate. "Mass estimate of black hole candidates GRS 1758-258 and GX 339-4 based on a transtion layer model of the accretion disk and a search for X-ray jets in GRS 1758-258 /." Diss., Digital Dissertations Database. Restricted to UC campuses, 2006. http://uclibs.org/PID/11984.
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Ibe, Chibuike. "Understanding the role of stress induced cell wall proteins in C. albicans cell wall compensatory response and pathogenicity." Thesis, University of Aberdeen, 2019. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=240548.
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Orkwis, Brianne. "Novel acid phosphatase in Candida glabrata suggests dynamic selective pressures on the phosphate starvation response." Click here for download, 2009. http://proquest.umi.com.ps2.villanova.edu/pqdweb?did=1934097791&sid=1&Fmt=2&clientId=3260&RQT=309&VName=PQD.
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Pettit, Michele L. "An assessment of health risk behaviors, values, and experiences among college students and GED candidates /." Available to subscribers only, 2006. http://proquest.umi.com/pqdweb?did=1196415421&sid=9&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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