To see the other types of publications on this topic, follow the link: Identification of novel genes.
Dissertations / Theses on the topic 'Identification of novel genes'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Identification of novel genes.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Travis, Kristina. "Identification of Novel Developmental Genes in Streptomyces Coelicolor." Otterbein University Distinction Theses / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=otbndist16204640123321.
Full text
2
Kotian, Shweta. "Identification of Novel Genes in BRCA1-Regulated Pathways." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366341897.
Full text
3
Archacki, Stephen R. "MOLECULAR IDENTIFICATION OF NOVEL GENES ASSOCIATED WITH ATHEROSCLEROSIS." Cleveland State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=csu1310652996.
Full text
4
Hu, Xiao Ping. "Identification and characterisation of novel cellulolytic genes using metagenomics." Thesis, University of the Western Cape, 2010. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_9293_1308049102.
Full textAbstract:
Metagenomics has been successfully used to discover novel enzymes from uncultured microorganisms in the environment. In this study, metagenomic DNA from a Malawian hot spring soil sample was used to construct a fosmid library. This metagenomic library comprised of more than 10000 clones with an average insert size of 30 kb, representing more than 3.0 x 108 bp of metagenomic DNA (equivalent to approximately 100 bacterial genomes). The library was screened for cellulase activity using a Congo red plate assay to detect zones of carboxymethylcellulose hydrolysis. This yielded 15 positive fosmid clones, of which five were further characterised for activity and thermostability using the 3, 5-dinitrosalicylic assay. Two of the five fosmids (XP008C2 and XP026G5) were selected for DNA pyrosequencing. The full sequence of the XP008C2 (29800bp) fosmid insert is presented in this study and genes thereon were chosen for further study.
5
Bennetts, Jennifer. "The identification and characterisation of novel genes in development /." [St. Lucia, Qld.], 2006. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe19375.pdf.
Full text
6
Looser, Jens. "Identification of two novel CVC domain-containing homeobox genes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1995. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ45845.pdf.
Full text
7
Haviland, Rachel. "Identification of Novel STAT3 Target Genes Associated with Oncogenesis." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3729.
Full textAbstract:
Cytokine and growth factor signaling pathways involving STAT3 are frequently constitutively activated in many human primary tumors, and are known for the transcriptional role they play in controlling cell growth and cell cycle progression. However, the extent of STAT3's reach on transcriptional control of the genome as a whole remains an important question. We predicted that this persistent STAT3 signaling affects a wide variety of cellular functions, many of which still remain to be characterized.
We took a broad approach to identify novel STAT3 regulated genes by examining changes in the genome-wide gene expression profile by microarray, using cells expressing constitutively-activated STAT3. Using computational analysis, we were able to define the gene expression profiles of cells containing activated STAT3 and identify candidate target genes with a wide range of biological functions. Among these genes we identified Necdin, a negative growth regulator, as a novel STAT3 target gene, whose expression is down-regulated at the mRNA and protein levels when STAT3 is constitutively active. This repression is STAT3 dependent, since inhibition of STAT3 using siRNA restores Necdin expression. A STAT3 DNA-binding site was identified in the Necdin promoter and both EMSA and chromatin immunoprecipitation confirm binding of STAT3 to this region. Necdin expression has previously been shown to be down-regulated in a melanoma and a drug-resistant ovarian cancer cell line. Further analysis of Necdin expression demonstrated repression in a STAT3-dependent manner in human melanoma, prostate and breast cancer cell lines.
These results suggest that STAT3 coordinates expression of genes involved in multiple metabolic and biosynthetic pathways, integrating signals that lead to global transcriptional changes and oncogenesis. STAT3 may exert its oncogenic effect by up-regulating transcription of genes involved in promoting growth and proliferation, but also by down-regulating expression of negative regulators of the same cellular processes, such as Necdin.
8
Chu, Youngmin. "Identification of Novel Genes Involved in Female Mating Choice." Case Western Reserve University School of Graduate Studies / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1364923180.
Full text
9
Vyas, Aditi. "Identification of Novel Stat92E Target Genes in Drosophila Hematopoiesis." Ohio University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1450868635.
Full text
10
Gregorio-King, Claudia C., and mikewood@deakin edu au. "The Identification of novel genes differentially expressed in Haemopoietic progenitor cells." Deakin University. School of Health Sciences, 2001. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20051111.113037.
Full textAbstract:
The biochemical and molecular processes that maintain the stem cell pool, and govern the proliferation and differentiation of haemopoietic stem/progenitor cells (HSPCs) have been widely investigated but are incompletely understood. The purpose of this study was to identify and characterise novel genes that may play a part in regulating the mechanisms that control the proliferation, differentiation and self-renewal of human HSPCs.
Reverse transcription differential display polymerase chain reaction (dd-PCR) was used to identify differences in gene expression between a HSPC population defined by expression of the CD34 phenotype, and the more mature CD34 depleted populations. A total of 6 differentially expressed complementary deoxyribonucleic acid (cDNA) sequences were identified. Four of these transcripts were homologous to well characterised genes, while two (band 1 and band 20) were homologous to unknown and uncharacterised partial gene sequences on the GenBank database and were thus chosen for further investigation.
The partial cDNA sequences for band 1 and band 20 were designated ORP-3 and MERP-1 (respectively) due to homologies with other well-characterised gene families. Differential expression of the ORP-3 and MERP-1 genes was confirmed using Taqman™ real-time polymerase chain reaction (PCR) with 3 - 4-fold and 4-10 -fold higher levels in the CD34+ fractions of haemopoietic cells compared to CD34- populations respectively. Additionally, expression of both these genes was down regulated with proliferation and differentiation of CD34+ cells further confirming higher expression in a less differentiated subset of haemopoietic cells.
The full coding sequences of ORP-3 and MERP-1 were elucidated using bioinformatics, rapid amplification of cDNA ends (RACE) and PCR amplification. The MERP-1 cDNA is 2600 nucleotides (nt) long, and localizes by bioinformatics to chromosome 7.. It consists of three exons and 2 introns spanning an entire length of 31.4 kilobases (kb). The MERP-1 open reading frame (ORF) codes for a putative 344 amino acid (aa) type II transmembrane protein with an extracellular C-terminal ependymin like-domain and an intracellular N-terminal sequence with significant homology to the cytoplasmic domains of members of the protocadherin family of transmembrane glycoproteins. Ependymins and protocadherins are well-characterised calcium-dependant cell adhesion glycoproteins. Although the function of MERP-1 remains to be elucidated, it is possible that MERP-1 like its homologues plays a role in calcium dependent cell adhesion. Differential expression of the MERP-1 gene in haemopoietic cells suggests a role in haemopoietic stem cell proliferation and differentiation, however, its broad tissue distribution implies that it may also play a role in many cell types. Characterization of the MERP-1 protein is required to elucidate these possible roles.
The ORP-3 cDNA is 6631nt long, and localizes by bioinformatics to chromosome 7pl5-p21. It consists of 23 exons and 22 introns spanning an entire length of 183.5kb. The ORP-3 ORF codes for a putative 887aa protein which displays the consensus sequence for a highly conserved oxysterol-binding domain. Other well-characterised proteins expressing these domains have been demonstrated to bind oxysterols (OS) in a dose dependant fashion. OS are hydroxylated derivatives of cholesterol Their biological activities include inhibition of cholesterol biosynthesis and cell proliferation in a variety of cell types, including haemopoietic cells. Differential expression of the ORP-3 gene in haemopoietic cells suggests a possible role in the transduction of OS effects on haemopoietic cells, however, its broad tissue distribution implies that it may also play a role in many cell types.
Further investigation of ORP-3 gene expression demonstrates a significant correlation with CD34+ sample purity, and 2-fold higher expression in a population of haemopoietic cells defined by the CD34+38- phenotype compared to more mature CD34+38+ cells. This finding, taken together with the previous observation of down-regulation of ORP-3 expression with proliferation and differentiation of CD34+ cells, indicates that ORP-3 expression may be higher in a less differentiated subset of cells with a higher proliferative capacity. This hypothesis is supported by the observation that expression of the ORP-3 gene is approximately 2-fold lower in differentiated HL60 promyelocytic cells compared to control, undifferentiated cells.
ORP-3 expression in HL60 cells during normal culture conditions was also found to vary with expression positively correlated with cell number. This indicates a possible cell cycle effect on ORP-3 gene expression with levels highest when cell density, and therefore the percentage of cells in G(0)/G(1) phase of the cell cycle is highest. This observation also correlates with the observation of higher ORP-3 expression in CD34+38-cells, and in CD34+ and HL60 cells undergoing OS induced and camptothecin induced apoptosis that is preceded by cell cycle arrest at G(0)/G(1). Expression of the ORP-3 gene in CD34+ HSPCs from UCB was significantly decreased to approximately half the levels observed in control cells after 24 hours incubation in transforming growth factor beta-1 (TGFâl). As ≥90% of these cells are stimulated into cell cycle entry by TGFâl, this observation further supports the hypothesis that ORP-3 expression is highest when cells reside in the G(0)/G(1) phase of the cell cycle. Data obtained from investigation of ORP-3 gene expression in synchronised HL60 cells however does not support nor disprove this hypothesis.
Culture of CD34+ enriched HSPCs and HL60 cells with 25-OHC significantly increased ORP-3 gene expression to approximately 1.5 times control levels. However, as 25-OHC treatment also increased the percentage of apoptotic cells in these experiments, it is not valid to make any conclusions regarding the regulation of ORP-3 gene expression by OS. Indeed, the observation that camptothecin induced apoptosis also increased ORP-3 gene expression in HL60 cells raises the possibility that up-regulation of ORP-3 gene expression is also associated with apoptosis,
Taken together, expression of the ORP-3 gene appears to be regulated by differentiation and apoptosis of haemopoietic progenitors, and may also be positively associated with proliferative and G(0)/G(1) cell cycle status indicating a possible role in all of these processes.
Given the important regulatory role of apoptosis in haemopoiesis and differential expression of the ORP-3 gene in haemopoietic progenitors, final investigations were conducted to examine the effects OS on human HSPCs. Granulocyte/macrophage colony forming units (CFU-GM) generated from human bone marrow (ABM) and umbilical cord blood (UCB) were grown in the presence of varying concentrations of three different OS - 7keto-cholesterol (7K-C), 7beta-hydroxycholesterol (7p-OHC) and 25-hydroxycholesterol (25-OHC). Similarly, the effect of OS on HL60 and CD34+ cells was investigated using annexin-V staining and flow cytometry to measure apoptosis. Reduction of nitroblue tetrazolium (NBT) was used to assess differentiative status of HL60 cells. CFU-GM from ABM and HL60 growth was inhibited by all three OS tested, with 25-OHC being the most potent. 25-OHC inhibited ≥50% of bone marrow CFU-GM and ≥95% of HL60 cell growth at a level of 1 ug/ml. Compared to UCB, CFU-GM derived from ABM were more sensitive to the effects of all OS tested. Only 25-OHC and 7(5-OHC significantly inhibited growth of UCB derived CFU-GM. OS treatment increased the number of annexin-V CD34+ cells and NBT positive HL60 cells indicating that OS inhibition of CFU-GM and HL60 cell growth can be attributed to induction of apoptosis and differentiation.
From these studies, it can be concluded that dd-PCR is an excellent tool for the discovery of novel genes expressed in human HSPCs. Characterisation of the proteins encoded by the novel genes ORP-3 and MERP-1 may reveal a regulatory role for these genes in haemopoiesis. Finally, investigations into the effects of OS on haemopoietic progenitor cells has revealed that OS are a new class of inhibitors of HSPC proliferation of potential relevance in vivo and in vitro.
11
Song, Gwon Hwa. "Identification of novel implantation-related genes in the ovine uterus." Texas A&M University, 2003. http://hdl.handle.net/1969.1/5782.
Full textAbstract:
The peri-implantation period in mammals is critical with respect to survival of
the conceptus and establishment of pregnancy. During this period of pregnancy,
reciprocal communication between ovary, conceptus, and endometrium is required for
successful implantation and placentation. Therefore, studies were conducted to indentify
and characterize novel endometrial genes important for implantation and conceptus
development in the ovine uterus.
The first and second studies defined the uterine expression of seven members of
the cathepsin (CTS) family of lysosomal proteases, and a secreted inhibitor of CTSL
called cystatin C (CST3) during the peri-implantation period. In addition, regulation of
CTS and CST3 by progesterone (P4) and interferon tau (IFNT) was evaluated. CTSL
was the most abundant CTS in the ovine ovine uterus and was also coordinately
expressed with CST3 in the endometrial epithelia and conceptus trophectoderm. CTSL
and CST3 were found to be novel P4-induced and IFNT-stimulated genes in the luminal
epithelial cells of the ovine endometrium.
The third study identified radical S-adenosyl methionine domain containing 2
(RSAD2) and interferon-induced with helicase C domain 1 (IFIH1) in the ovine uterus.
Results of this study indicated that IFNT induces RSAD2 and IFIH1 in a P4-independent
manner in the stroma, immune cells, and glands of the ovine endometrium. These two
genes are proposed to have biological roles in the establishment of uterine receptivity to
the conceptus during implantation.
The fourth study characterized endometrial expression of stanniocalcins (STC)
during pregnancy. STC1 appeared in the endometrial glands on Day 18 of pregnancy, increased from Days 18 to 80, and remained abundant through Day 120 of gestation. In
addition, this study demonstrated that STC1 is induced by P4 and increased by placental
hormones, such as placental lactogen (CSH1) and growth hormone (GH), in the ovine
endometrial glands.
Collectively, these studies identified genes that are expected to be critical to
unraveling the mechanism(s) of reciprocal fetal-maternal interactions required for
successful implantation and pregnancy. A more complete understanding of these genes
will be important for developing therapeutic strategies to prevent, treat and/or diagnose
infertility in domestic animals and humans, because they are biomarkers of P4 and/or
IFN effects.
12
Tse, Ka-yu. "Identification of novel methylated genes in patients with endometrial cancers /." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38284893.
Full text
13
Tse, Ka-yu, and 謝嘉瑜. "Identification of novel methylated genes in patients with endometrial cancers." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B45011473.
Full text
14
McGregor, Nathaniel Wade. "The identification of novel susceptibility genes involved in anxiety disorders." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/95859.
Full textAbstract:
Thesis (PhD)--Stellenbosch University, 2014.ENGLISH ABSTRACT: The etiology of anxiety disorders remains incompletely understood. Clear evidence for a genetic component has been proposed; however, there is also an increasing focus on environmental factors and the interaction between these and the genetic components that may mediate (anxiety) disorder pathogenesis. No single gene or genetic component has been explicitly identified as being involved in the development of anxiety disorders. This is most likely due to a number of reasons, which include, for example, the heterogeneity of anxiety disorders, the contribution of environmental factors and methodological limitations (e.g. small sample size) of research studies. Until now, genetic association studies usually focused on one particular psychiatric disorder at a time. However, with the difficulty in identifying susceptibility genes and/or loci in heterogeneous disorders like obsessive-compulsive disorder and other conditions in the anxiety spectrum, it is perhaps timely to consider multivariate genetics and epidemiological studies in a number of disorders sharing a core characteristic – such as anxiety. In addition to genetic underpinnings, a number of environmental variables have also been identified as risk factors for pathological anxiety, including adverse life events like childhood physical and sexual abuse. The hypothesis for this project is that a pre-existing genetic vulnerability (or genetic risk) interacts with the impact of adverse life events to result in the development of one or more anxiety disorder(s). Considering phenotypic overlap amongst the anxiety disorders, it is likely that diverse networks of genes and/ or interacting pathways are responsible for the phenotypic manifestations observed. Sprague Dawley rats exhibiting behaviours indicative of anxiety in the context of environmental stressors (maternal separation and restraint stress) were used as model for the identification of novel susceptibility genes for anxiety disorders in humans. The striatum has previously been implicated as a candidate in the brain architecture of anxiety pathogenicity, and is also a site exhibiting a high degree of synaptic plasticity. The synaptic plasticity pathway was investigated using the dorsal striatum of the rat brain and several genes were identified to be aberrantly expressed in “anxious” rats relative to controls (Mmp9, Bdnf, Ntf4, Egr2, Egr4, Grm2 and Arc). In humans, it was found that the severity of early adversity was significantly and positively associated with the presence of an anxiety disorder in adulthood. When the human homologues of the susceptibility candidate genes that were identified using the animal model were screened in a human cohort of patients with obsessive-compulsive disorder (OCD), panic disorder (PD) or social anxiety disorder (SAD) (relative to controls), five single nucleotide polymorphisms (SNPs) were found to be significantly associated with these conditions. Four of these SNPs were also found to significantly interact with the severity of childhood trauma. Haplotype analysis of variants within the identified susceptibility candidates revealed novel haplotype associations, four of which are located in the MMP9 gene. Notably, this the first study to link these particular mutations in the MMP9 gene with anxiety disorders and this finding is consistent with previous work suggesting that MMP9 is involved in conditions like cardiovascular disease and cancer which have been associated with increased prevalence of anxiety disorders. In conclusion, this project yielded important findings pertaining to the etiology of anxiety disorders. The use of a combined anxiety disorders cohort (OCD, PD and SAD) may suggest that the associations found here may hold true for anxiety disorders in general and not only for a particular clinically delineated condition. Childhood trauma was confirmed as an increased susceptibility risk for anxiety disorders. Also, this research contributed several novel susceptibility genes (MMP9, EGR2, EGR4, NTF4, and ARC), five significant SNP associations, four significant SNP-environment interactions and five haplotype associations (within MMP9 and BDNF) as candidates for anxiety pathogenicity. The identified polymorphisms and haplotypes were demonstrated to be associated with susceptibility to anxiety disorders in a gene-environment correlation and gene-environment interaction.
AFRIKAANSE OPSOMMING: Die oorsake van angssteurings word steeds nie volledig verstaan nie. Daar is duidelike bewyse vir 'n genetiese komponent, maar daar is ook toenemende fokus op omgewingsfaktore en die interaksie tussen hierdie omgewingsfaktore en genetiese komponente by angssteurings. Geen enkele geen of genetiese komponent is al geïdentifiseer as diè wat betrokke is by die ontwikkeling van angssteurings nie. Dit is waarskynlik weens 'n aantal redes, wat byvoorbeeld, die heterogeneïteit van angssteurings, die bydrae van omgewingsfaktore en metodologiese beperkings (bv. klein steekproef) van die navorsingstudies, insluit. Verder het genetiese assosiasiestudies tot nou toe gewoonlik net op een spesifieke psigiatriese versteuring op 'n slag gefokus. Maar, gegewe die uitdaging om vatbaarheidsgene en / of loci in heterogene steurings soos obsessief – kompulsiewe steuring (OKV) en ander toestande op die angsspektrum te identifiseer, is dit tyd om genetiese en kliniese studies in ‘n aantal steurings - met ‘n oorvleuende kern-element soos angs -, gesamentlik te oorweeg. Bykomend tot die genetiese boustene, is ‘n aantal omgewingsveranderlikes soos traumatiese lewenservarings tydens die kinderjare as risikofaktore vir patologiese angs geidentifiseer. Die hipotese vir hierdie projek is dat daar 'n interaksie tussen genetiese kwesbaarheid (of genetiese risiko) en traumatiese lewensevarings is en dat dit tot die ontwikkeling van 'n / veelvoudige angssteuring(s) kan lei. Inaggenome die fenotipiese oorvleueling tussen die angssteurings, is dit waarskynlik dat diverse netwerke van gene en / of interaktiewe geen-paaie vir die manifestasie van hierdie toestande verantwoordelik is. Sprague Dawley-rotte met gedragswyses aanduidend van angs, in die konteks van omgewingstressore (d.i. skeiding van die ma-rot en bedwang-stres [restraint stress]), is as model gebruik vir die identifisering van nuwe vatbaarheidsgene vir angssteurings in mense. Die striatum is voorheen as ‘n kandidaat in die brein-argitektuur van patologiese angs voorgehou, en is ook ‘n plek met ‘n hoë mate van sinaptiese plastisiteit. Die sinaptiese plastisiteit is ondersoek deur te fokus op die dorsale striatum van die rotbrein en daar is verskeie gene gevind wat anders is in “angstige” rotte in vergelyking met kontroles (Mmp9, Bdnf, Ntf4, Egr2, Egr4, Grm2 en Arc). In mense is daar gevind dat die ernstigheidsgraad van vroeë trauma beduidend en positief met die teenwoordigheid van ‘n angssteuring tydens volwassenheid verband hou. Toe die menslike ekwivalente van die vatbaarheidsgene wat met die dieremodel geïdentifiseer is in ‘n mens-kohort met obsessief-kompulsiewe steuring (OKS), panieksteuring (PS) en sosiale angssteuring (SAS) ondersoek is, is gevind dat daar 5 enkele nukleotied polimorfismes (ENPs) is wat met die toestande verband hou. Daar is ook gevind dat vier van hierdie ENPs beduidend verband hou met die ernstigheidsgraad van trauma tydens die kinderjare. Haplotipe analise van variante binne die geïdentifiseerde vatbaarheidsgene het op nuwe haplotipe assosiasies – waarvan 4 op die MMP9-geen geleë is – gedui. Hierdie is dus die eerste studie wat gevind het dat dié spesifieke mutasies van die MMP9-geen met angssteurings verband hou. Hierdie bevinding strook met vorige werk wat daarop dui dat die MMP9-geen by toestande soos kardiovaskulêre siekte en kanker wat ook met verhoogde voorkoms van angssteurings verband hou, betrokke is. Ter afsluiting kan ons sê dat hierdie projek belangrike bevindinge oor die oorsake van angssteurings gemaak het. Die gebruik van ‘n gekombineerde angssteurings-kohort (OKS. PS en SAS) kan moontlik suggereer dat die assosiasies wat ons hier gevind het, waar is vir alle angssteurings en nie net vir ‘n spesifieke afgebakende toestand nie. Traumatiese ervarings tydens die kinderjare is ook bevestig as ‘n risiko vir die ontwikkeling van angssteurings. Hierdie navorsing het ook verskeie nuwe vatbaarheidsgene (MMP9, EGR2, EGR4, NTF4, en ARC), 5 beduidende ENP assosiasies, 4 beduidende ENP-omgewings-interaksies en 5 haplotipe assosiasies (by MMP9 en BDNF) geïdentifiseer as moontlike kandidate wat ‘n rol speel by die ontstaan van patologiese angs. Daar is ook gevind dat die geïdentifiseerde polimorfismes en haplotipes met vatbaarheid vir angssteurings in ‘n geen-omgewing- korrelasie en geen-omgewing- interaksie verband hou. Stellenbosch University http://scholar.sun.ac.za
15
Coler, Rhea Nadine. "Identification and characterization of novel antigen genes of Mycobacterium tuberculosis /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/9281.
Full text
16
Almutairi, Mikhlid Hammad. "Identification of novel human cancer-testis-antigen genes in cancers." Thesis, Bangor University, 2014. https://research.bangor.ac.uk/portal/en/theses/identification-of-novel-human-cancertestisantigen-genes-in-cancers(015fda5b-5bd3-42c1-a610-811f0acde19a).html.
Full text
17
Cabral, Vitor Hugo. "Identification of novel Candida albicans genes involved in biofilm formation." Paris 7, 2012. http://www.theses.fr/2012PA077224.
Full textAbstract:
Candida albicans est une levure polymorphe pathogène commensale ou opportuniste, causant des infections des muqueuses ou même des infections systémiques souvent mortelles. C. Albicans est capable de former des biofilms (cellules de levure, pseudohyphes et hyphes incluses dans une matrice polymère extracellulaire) qui se développent sur les surfaces biotiques ou abiotiques et présentent des traits phénotypiques spécifiques (haute résistance aux drogues). L'architecture des biofilms dépend des transitions levure-hyphe et des protéines de surface qui permettent les interactions hyphe-hyphe et confèrent la cohésion à la structure. Le but principal de mon projet de thèse a été d'identifier et caractériser les régulateurs additionnels de la formation de biofilm qui peuvent devenir des cibles pour prévenir la formation des biofilms ou les éliminer. J'ai construit une collection de souches de surexpression de C. Al bicans et l'ai examinée dans un modèle médium throughput afin d'identifier les gènes dont la surexpression influence la formation de biofilm. Un groupe de souches, chacune surexprimant un gène codant une protéine glycosylphosphatidylinositol (GPI-)ancrée (PGAs), présentait une augmentation de l'occupation dans le biofilm formé par toutes les souches de surexpression. J'ai étudié ces gènes et montré qu'ils utilisent des mécanismes différents pour la formation des biofilms. Cette étude montre qu'une collection ORFeome peut être utilisée pour étudier le rôle de quelques gènes et des familles de gènes dans la formation de biofilmsCandida albicans is a polymorphic fungus that exists as either a commensal or an opportunistic pathogen, causing mucosal infections and even life-threatening systemic infections. C. Albicans is able to form biofilms (yeast, pseudohyphal and hyphal cells embedded in an extracellular polymeric matrix) that grow on biotic or abiotic surfaces and display specific phenotypic traits (as a high résistance to drugs). Biofilm architecture depends on the yeast-to-hypha transition and surface proteins that mediate hypha-hypha interactions and confer cohesiveness. The main aim of my thesis project will be to identify and characterize additional regulators of biofilm formation that may become targets for preventing or eliminating biofilms. A collection of C albicans over-expression strains, was established and screened using medium throughput biofilm models from which genes whose over-expression alters biofilm formation were identified. Notably, a subset of strains, each overexpressing a gène encoding for glycosylphosphatidylinositol (GPI)-anchored proteins (PGAs), showed increased occupancy of a biofilm formed by a pool of ail thé overexpression strains. We have focused our study on PGA genes that have an effect on biofilm formation and shown that, despite the common higher strain occupancy on a multi-strain biofilm as a result of their overexpression, the mechanisms by which they reach this end differ. This study acts as a proof-of-principle that the ORFeome collection is a useful tool to study biofilm formation, providing insights into the contribution of individual genes as well as complete or partial gene families
18
Guo, Ling. "Identification of novel SLE susceptibility genes by microarray analysis and candidate gene association study." Oklahoma City : [s.n.], 2008.
Find full text
19
Sanhueza, Cubillos Mario Andrés. "Identification of novel genes interacting with DVAP, the causative gene of ALS8 in humans." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/21080.
Full textAbstract:
Amyotrophic lateral sclerosis (ALS) is a major neurodegenerative disease caused by the death of motor neurons leading to paralysis. Mechanisms underlying the pathogenesis of the disease remain unknown but with the identification of causative genes from ALS patients, some processes have been linked to the disease. One of these genes is VAPB, a highly conserved protein involved in lipid transfer, vesicle metabolism and synaptic morphology. We modeled in Drosophila the disease-linked P56S mutation (DVAP-P58S) and observed with the expression of this allele neurodegeneration in the eye and loss of motor performance. These phenotypes provide an excellent opportunity to use fly’s genetics to find novel genetic interactors of DVAP and understand ALS pathomechanism. Therefore, we carried out a large scale genetic screen by crossing the ALS model with a collection of P-element overexpression lines. After the analysis of 1183 lines, we obtained 71 modifier lines that suppress DVAP-induced neurodegeneration and 14 lines that enhance this phenotype, decreasing furthermore the eye size and viability of the offspring. To confirm that the effect of modifier lines was caused by a specific gene, we validated them with independent alleles of those genes. Using different sources, we were able to confirm the effect of 63 of the 85 modifiers, providing a strong confirmation of their effect. When we studied the effect of the modifier genes co-expressed with DVAP-P58S in the nervous system, we detected that 46 lines presented the same modifying effect in adult viability and 58 in the motor performance of the adult offspring. Considering the stronger readouts, we obtained 42 genes as novel high confidence DVAP genetic interactors. To understand furthermore the way they are affecting DVAP neurodegeneration, we carried out a series of bioinformatic analyses using Drosophila and human databases. Lipid droplets, vesicle metabolism and cell proliferation appear as the most important categories found in the screen, all processes conserved when analysed with human orthologs of the modifiers. Further characterisation of the endocytosis-linked modifier Rab5 and the predicted DVAP-interactors Rab7 and Rab11, showed that the suppression effect is not only confirmed in vivo but is also conserved in human tissue from ALS patients. These data validate our genetic screen and at the same time open novel opportunities to understand ALS mechanisms and find possible therapeutic targets.
20
Ganea, Karin. "Identification and characterisation of novel antidepressant-responsive genes in mouse brain." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-99940.
Full text
21
Sadler, Amanda J. "Identification of novel genes associated with endocrine resistance in breast cancer." Thesis, University of Reading, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485503.
Full textAbstract:
The overall aims of this project were to identify rnRNAs overexpressed or underexpressed as MCF7 human breast cancer cells progress to growth pathways independent of oestrogen and resistant to the antioestrogen, fulvestrant. Growth of oestrogen maintained and long-term oestrogen deprived MCF7,cells with or without la-8M l7p-oestradiol for 7 days enabled the comparison of expression profiles to identify a number of oestrogen regulated genes, in addition to a number of genes differentially expressed in long-term oestrogen deprived cells compared to cells which had been deprived of oestrogen for just? days. Comparison of expression profiles for oestrogen maintained and oestrogen deprived cells following long-term exposure to fulvestrant revealed large alterations in a number of gene expression levels, particularly in the oestrogen maintained cells. Adrenomedullin may have a role in tumour survival and angiogenesis and consistent upregulation of adrenomedulin mRNA was observed during progression to oestrogen insensitivity in duplicate microarray experiments. Real-time RTPCR was able to confirm the increase in mRNA levels in long-term oestrogen deprived cells. Immunofluorescent staining using a monoclonal antibody specific for adrenomedullin showed an increase in the amount of protein in long-term oestrogen deprived cells. Following short and long-term treatment with tamoxifen and fulvestrant the abundance of adrenomedullin rnRNA was increased in oestrogen maintained cells but not in the long-term oestrogen deprived cells. Real time RT-PCR analysis of the GAiA family of transcription factors revealed a reciprocal relationship between GATA3 and GATA6 in ER positive cells and ER negative cells where GATA6 showed highest expression in the ER negative cells and GATA3 was highly expressed in the ER positive cells. Changes were observed in levels of all six of the GATA factors following long-term oestrogen deprivation indicating a functional role for these transcription factors in progression to endocrine resistance. Many potential targets have been identified by the use of microarrays but further validation of cell lines and tumour samples is required to examine the importance of these as possible markers of endocrine resistance in breast tumours.
22
Horpaopan, Sukanya [Verfasser]. "Identification of Novel Causative Genes for Colorectal Adenomatous Polyposis / Sukanya Horpaopan." Bonn : Universitäts- und Landesbibliothek Bonn, 2015. http://d-nb.info/1077289529/34.
Full text
23
Lefebvre, Valerie. "Identification of Novel Parkinson’s Disease Genes Involved in Parkin Mediated Mitophagy." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/30222.
Full textAbstract:
Mitochondrial dysfunction has been implicated as one of the primary causes of Parkinson's disease (PD). The proteins PINK1, a serine-threonine kinase, and Parkin, an E3 ubiquitin ligase, are mutated in many genetic cases of PD. In healthy individuals, Parkin is recruited to damaged mitochondria and leads to autophagic degradation of mitochondria in a process termed mitophagy. Following depolarization of the mitochondrial membrane, PINK1 is stabilized on the outer mitochondrial membrane, and triggers Parkin translocation from the cytosol to mitochondria. Precisely how this phenomenon is regulated is still unclear. We employed RNA interference (RNAi) technology in a 384-well format to identify novel genes that are required for Parkin recruitment to mitochondria. We identified ATPase inhibitory factor 1 (IF1) as the strongest hit required for Parkin recruitment following treatment with the protonophore CCCP. We show that IF1 is upstream of PINK1 and Parkin, and required to sense mitochondrial damage by allowing the loss of membrane potential. In cells treated with CCCP, the absence of IF1 permits the ATP synthase to run freely in reverse, consuming ATP to maintain potential across the inner mitochondrial membrane, thus blocking PINK1 and Parkin activation. Interestingly, Rho0 cells, that lack mitochondrial DNA, have downregulated endogenous expression of IF1 in order to maintain mitochondrial function. Overexpression of IF1 in Rho0 cells results in the depletion of mitochondrial membrane potential and the initiation of mitophagy. These data demonstrate a unique role for IF1 in the regulation of mitochondrial quality control that has not been explored in the etiology of PD.
24
Labermaier, Christiana. "Identification of novel candidate genes involved in individual antidepressant treatment response." Diss., Ludwig-Maximilians-Universität München, 2015. http://nbn-resolving.de/urn:nbn:de:bvb:19-179575.
Full text
25
Groet, Jurgen. "Physical mapping and identification of novel genes in human chromosome 21q11." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312003.
Full text
26
Davies, Andrea. "Identification of novel p53-dependent genes in etoposide-treated gastrointestinal cells." Thesis, University of Liverpool, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.422990.
Full text
27
Smith, Shavannor Michelle. "Identification and characterization of Rp1 genes with novel phenotypes in maize /." Search for this dissertation online, 2004. http://wwwlib.umi.com/cr/ksu/main.
Full text
28
Eve, A. M. J. "Identification and functional analyses of novel genes involved in haemovascular development." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1473223/.
Full textAbstract:
Characterising the transcriptome of the haemangioblast is of therapeutic interest. By profiling the precursor to both blood and endothelial cells, important candidate genes can be identified for further study, and contribute to our understanding of vascular development and disease. Using previously generated RNA-sequencing data, novel genes with roles in haemovascular development were functionally characterised. Previously, the Wnt signalling antagonist Tmem88a was shown to be necessary for primitive erythropoiesis. Using qPCR and in situ hybridisation the expression profile of tmem88a was characterised. Morpholino knockdown of tmem88a in the zebrafish reduces the number of erythrocytes and myelocytes, according to qPCR and histological stains. Erythro-myelopoiesis was rescued by small molecule inhibition of the Wnt signalling pathway. In addition, a tmem88a mutant line was generated using TALENs, and the tmem88a mutant did not phenocopy tmem88a knockdown embryos. Although the tmem88a mutant is yet to be validated as a genetic knockout at the protein level, this may be an example of off-target effects from morpholino injection. Future work will validate the mutant and investigate discrepancies between morphant and mutant phenotypes. A morpholino knockdown screen showed that laminin γ3 is necessary for zebrafish para- chordal chain development. Use of the CRISPR-Cas9 system in F0 embryos also caused the same lymphatic phenotype, although a homozygous knockout line was not generated. The expression profile of lamc3 was characterised using in situ hybridisation and qPCR. Single-blastomere injections determined that γ3 was required in a non-cell autonomous fashion. Analyses using morpholino knockdown showed that γ3-deficient embryos had improper migration of the rostral primary motor neurons, preventing formation of the parachordal chain and thoracic duct. Furthermore, Netrin-1 protein was delocalised in lamc3 knockdown embryos, explaining the latter phenotypes. Here, I suggest a model whereby γ3 binds Netrin-1 to facilitate migration of motor neurons, and lymphatic endothelial cells.
29
Lornage, Xavière. "Identification and functional characterization of novel genes implicated in congenital myopathies." Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ067.
Full textAbstract:
Les myopathies congénitales sont des maladies génétiques sévères caractérisées par une faiblesse musculaire très invalidante de début infantile. Afin d’identifier de nouvelles causes génétiques, nous avons séquencé les exomes de patients myopathes qui ne disposaient pas de diagnostic moléculaire et leur analyse a mis en évidence deux nouveaux gènes de myopathie. MYPN et ACTN2 codent pour deux protéines structurales du sarcomères appelées myopalladine et alphaactinine-2. Afin d’étudier l’impact des mutations sur la fonction de la protéine et sur la physiologie du muscle, des analyses moléculaires et fonctionnelles ont été réalisées en modèles cellulaires et animaux. Les mutations dans MYPN induisent une perte de la protéine, et dans les muscles de souris, l’alpha-actinine-2 mutée conduit à une faiblesse musculaire et génère des défauts structuraux similaires à ceux retrouvés chez les patients. Ces résultats ont un impact direct sur la prise en charge des patients et sur le conseil génétique, sur la compréhension de voies de signalisation fondamentales pour la physiologie musculaire, et mettent en évidence de nouvelles cibles thérapeutiquesCongenital myopathies are severe genetic muscle diseases characterized by a disabling early-onset muscle weakness. In order to identify new genetic causes, we sequenced the exomes of molecularly undiagnosed congenital myopathy patients, and their analysis highlighted two novel myopathy genes. MYPN and ACTN2 encode two structural sarcomeric proteins called myopalladin and alphaactinin-2. To evaluate the impact of the mutations on the protein function and on muscle physiology, molecular and functional analyses were performed in cell and animal models. The MYPN mutations resulted in loss of myopalladin expression, and in mouse muscles, mutated alpha-actinin-2 led to muscle weakness and structural defects similar to those observed in the patient muscles. These results have a direct impact on the disease management of the patients and on genetic counselling, provide a better understanding of the signaling pathways required for muscle physiology, and highlight novel therapeutic targets
30
Warner, Adam Dennis. "Identification of novel genes affecting body wall muscle in Caenorhabditis elegans." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31429.
Full textAbstract:
Muscular diseases affect many people worldwide. While we have learned much
about the sarcomere, the basic building block of muscle cells, there are still numerous
questions that remain to be answered. In fact, all of the proteins involved in the formation
and maintenance of the sarcomere have yet to be catalogued and studied. We must learn
more about proteins expressed in muscle and how they interact so that better treatments for
myopathies can be produced. In this thesis, several novel sarcomeric proteins have been
identified using Caenorhabditis elegans as a model organism.
A list of genes expressed in muscle cells was compiled using available Serial
Analysis of Gene Expression (SAGE) and microarray data. By eliminating or severely
reducing the expression of each gene using RNA interference (RNAi), we were able to
determine which genes were required for proper myofilament organization. Of 23 genes
known to affect muscle, 16 were identified using this methodology. In total 119 genes were
found to be necessary for proper myofilament organization, 103 of which are genes without a
previously characterized role in muscle.
In addition, a bioinformatics based screen that utilized tissue specific SAGE data in
C. elegans yielded a number of potential candidate muscle affecting genes, and one,
C28H8.6 was further studied. C28H8.6 consists of both an ' a ' and a ' b ' isoform, one of
which, C28H8.6a has 4 LIM domains and bears striking sequence similarity to the focal
adhesion protein paxillin. In animals homozygous for a mutation that knocks out both
isoforms of C28H8.6, movement is uncoordinated and development is arrested at the first
larval stage. We have demonstrated using isoform specific RNAi that knocking down
expression of C28H8.6b has no observable effect on development, while C28H8.6a is
required for proper larval growth and movement. Further study on this isoform verified that
C28H8.6a co-localizes to dense bodies with a- actinin and is required for proper organization
of myofilaments within the sarcomere.Medicine, Faculty of
Medical Genetics, Department of
Graduate
31
Weraarpachai, Woranontee. "Identification and characterization of novel genes involved in cytochrome c oxidase deficiencies." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107626.
Full textAbstract:
In mitochondria, ATP is generated by oxidative phosphorylation (OXPHOS), a process that requires five multimeric enzyme complexes. Electrons are passed along the first four enzyme complexes (complex I-IV) that make up the mitochondria respiratory chain, releasing energy that is stored in the form of a proton gradient across the mitochondrial inner membrane, and is subsequently used by the ATP synthase (complex V) to produce ATP. Complex IV or cytochrome c oxidase (COX) is the terminal enzyme in the mitochondrial respiratory chain, catalyzing the oxidation of cytochrome c by molecular oxygen. It contains 13 structural subunits in mammals, 3 of which are encoded by mitochondrial DNA. Cytochrome c oxidase deficiencies can be caused by mutations in either mitochondrial or nuclear DNA. COX deficiency can result from mutations in the structural subunits or factors necessary for the assembly of the enzyme complex. In this thesis, two novel genes mutated in two subjects with COX deficiency have been identified. First, we identified a specific defect in the synthesis of the mtDNA-encoded COX subunit 1 (COX I) in a pedigree segregating late-onset Leigh Syndrome and COX deficiency. We mapped the defect to chromosome 17q by microcell-mediated chromosome transfer and identified a homozygous single base pair insertion causing a premature stop in CCDC44, renamed TACO1 for translational activator of COX I. TACO1 is a member of a large family of hypothetical proteins containing a conserved DUF28 domain that localizes to the mitochondrial matrix. Expression of the wild-type cDNA restored TACO1 protein and rescued the translation defect. TACO1 is the first specific mitochondrial translational activator identified in mammals. Respiratory competence, mitochondrial translation and COX activity were normal in yeast strain deleted for the orthologue YGR021w, suggesting that TACO1 has evolved a novel function in mammalian mitochondrial translation. Secondly, we studied a family in which the subject presented with severe congenital lactic acidosis and dysmorphic features associated with a COX assembly defect and a specific decrease in the synthesis of COX I. Using a combination of microcell mediated chromosome transfer, homozygosity mapping, and transcript profiling we mapped the gene defect to chromosome 12, and identified a homozygous missense mutation causing an amino acid change from methionine to isoleucine in C12orf62, a gene apparently restricted to the vertebrate lineage. Expression of the wild-type cDNA restored C12orf62 protein levels, and rescued the COX I synthesis and COX assembly defect. C12orf62 is a very small (6 kDa), uncharacterized, single transmembrane protein that localizes to mitochondria. COX I, II and IV subunits co-immunoprecipitated with an epitope-tagged version of C12orf62, and 2D BN-PAGE analysis of newly synthesized mitochondrial COX subunits in subject fibroblasts showed that COX assembly was impaired, and the nascent enzyme complex unstable. We conclude that C12orf62 is required for coordinating the early steps of COX assembly with the synthesis of COX I.Dans les mitochondries, l'ATP est généré par la phosphorylation oxydative (PHOSOX), un processus qui nécessite cinq complexes enzymatiques multimériques. Le transport des électrons le long des quatre premiers complexes enzymatiques (complexes I-IV) libère l'énergie qui est stockée sous la forme d'un gradient de protons à travers la membrane interne mitochondriale et est ensuite utilisée par l'ATP synthétase (complexe V) pour produire de l'ATP. Le complexe IV ou cytochrome C oxydase (COX) est l'enzyme terminale de la chaîne respiratoire mitochondriale, catalysant l'oxydation du cytochrome c par l'oxygène moléculaire. Il contient 13 sous-unités structurelles chez les mammifères, dont 3 sont codées par l'ADN mitochondriale. Les déficiences en cytochrome C oxydase peuvent être causées par des mutations dans l'ADN mitochondriale ou l'ADN nucléaire. Les carences en COX peuvent être liées à des mutations dans les sous-unités structurelles ou à des mutations dans des facteurs nécessaires à l'assemblage du complexe enzymatique. Dans cette thèse, deux nouveaux gènes mutés ont été identifiés et caractérisés dans deux patients présentant un déficit en COX. Premièrement, nous avons identifié un défaut spécifique dans la synthèse de la sous-unité COX 1 de l'ADN mitochondriale (COX I) dans un pedigree présentant une apparition tardive du syndrome de Leigh et une carence en COX. Nous avons cartographié le défaut génétique au chromosome 17q par la technique de transfert de chromosomes à médiation microcellulaire. Nous avons, par la suite, identifié une mutation homozygote, une insertion d'une base causant l'apparition prématurée d'un codon stop qui entraîne l'arrêt de la synthèse de la protéine CCDC44, renommé TACO1 pour activateur de la traduction de la COX I. TACO1 est membre d'une famille de protéines contenant un domaine conservé à fonction inconnue, nommé DUF28, qui se localise à la matrice mitochondriale. L'expression de l'ADN complémentaire de type sauvage de TACO1 compense le défaut de traduction de COX I. TACO1 est le premier activateur spécifique de la traduction mitochondriale à être identifié chez les mammifères. Il a été observé que l'absence (knock-down) du gène codant l'orthologue de TACO1 chez la levure, le YGR021w, ne perturbait pas la compétence des voies respiratoires, la traduction mitochondriale, ni l'activité de COX. Ceci suggère que TACO1 a évolué et a acquérit une nouvelle fonction dans la traduction mitochondriale chez les mammifères. Deuxièmement, nous avons étudié une famille dans laquelle le sujet présentait une acidose lactique congénitale et dysmorphie associée à un défaut d'assemblage et une diminution de l'activité enzymatique de la COX due à un défaut spécifique dans la traduction de COX I. En utilisant une combinaison de techniques dont le transfert de chromosomes à médiation microcellulaire, la cartographie d'homozygotie et le profilage de transcription, nous avons cartographié le gène défectueux sur le chromosome 12. Nous avons identifié une mutation faux sens à l'état homozygote provoquant un changement d'acide aminé de méthionine en isoleucine dans le gène C12orf62, un gène qui semble restreint à la lignée des vertébrés. L'expression de l'ADN complémentaire de type sauvage de C12orf62 a restauré la synthèse de COX I et le défaut d'assemblage de la COX. C12orf62 est une très petite protéine transmembranaire (6 kDa), non caractérisée, qui se localise aux mitochondries. Les sous-unités COX I, II et IV co-immunoprécipitent avec un épitope marqué de la protéine C12orf62. Les analyses de bleu d'électrophorèse sur gel de polyacrylamide natif (BN-PAGE) en deux dimensions pour les sous-unités nouvellement synthétisées de la COX mitochondriale ont démontré que la COX assemblée est altérée et que le complexe enzymatique naissant est instable dans les fibroblastes du patient atteint. Nous concluons que C12orf62 est nécessaire pour coordonner les étapes précoces de l'assemblage de la COX et de la synthèse de COX I.
32
Chikkaballi, Anne Gowda Deepak. "Identification of novel Salmonella virulence genes involved in invasion and intracellular survival /." Berlin : Mbv, 2009. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=018885733&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
Full text
33
Maibaum, Michael Anthony. "The identification of novel susceptibility genes in the lupus prone BXSB mouse." Thesis, Imperial College London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271233.
Full text
34
McDade, Donna Marie. "Identification of novel target genes for the plasticity-related transcription factor Zif268." Thesis, University of Glasgow, 2007. http://theses.gla.ac.uk/28/.
Full textAbstract:
Activity based alterations in synaptic connectivity are thought to underlie the processes involved in learning and memory. Measurable changes in neuronal activation by long-term potentiation (LTP) are widely investigated as a possible cellular correlate of this phenomenon, as it can be induced quickly to elicit long-lasting modifications. These long-term changes in the activity of neuronal circuits are sustained by an altered pattern of gene expression and protein synthesis. The inducible transcription factor Zif268 has been implicated in almost all models of neuronal plasticity. Downstream targets of zif268 are widely believed to contribute to the duration and stabilisation of NMDA receptor dependent LTP which, in turn, can be linked to various models of learning and memory. However, these downstream targets are only just starting to receive attention. By utilising a wide range of contemporary neuroscience techniques covering molecular & cell biology approaches, this thesis proposes two known proteins, gephyrin and ubiquilin, as well as a novel gene (urma), as potential downstream targets of Zif268. Both gephyrin and ubiquilin are associated with GABAA receptors at inhibitory synapses. Gephyrin is thought to cluster and anchor GABAA receptors at postsynaptic sites whilst ubiquilin is reported to regulate receptor surface expression. We found that gephyrin mRNA and protein expression levels were downregulated in response to increased levels of zif268 by transient transfection in PC-12 cells and NMDA stimulation in primary cultured cortical neurones. In addition, ubiquilin mRNA and protein levels were also downregulated within the same experimental paradigms, implying that both gephyrin and ubiquilin are downstream transcriptional targets of this plasticity-related gene. A previously reported microarray experiment (James et al. 2005) contained 144 ESTs significantly affected by the transient transfection of Zif268 in PC-12 cells compared to control. Bioinformatic analyses of these tags revealed interesting genomic areas pertaining to little published information. After further investigation, EST AI169020 revealed a novel transcript that was downregulated in response to NMDA treatment of primary cortical neurones. Additional data mining suggests that urma may be a rarely expressed transcription factor. Basal levels of urma mRNA were also decreased in the Zif268 knockout mouse, as were ubiquilin mRNA levels. Zif268 is a regulatory immediate early gene, activating or suppressing downstream targets that play a role in the duration and stabilisation of LTP. These results indicate that gephyrin and ubiquilin are potential mediators of NMDA receptor-dependent plasticity, by modifying inhibitory-signalling. In addition, Zif268 may actively suppress a novel plasticity-related transcription factor, urma. These findings may underlie important processes in learning and memory.
35
Gilmore, Paula. "The identification of novel genes involved in chemotherapy resistance in ovarian cancer." Thesis, Queen's University Belfast, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361248.
Full text
36
Coffer, Paul James. "The identification, cloning and characterisation of novel mammalian protein-serine kinase genes." Thesis, Open University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293298.
Full text
37
Connolly, David John. "Identification of novel class 1 genes in the mouse major histocompatibility complex." Thesis, Open University, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304886.
Full text
38
Chikkaballi, Anne Gowda Deepak. "Identification of novel Salmonella virulence genes involved in invasion and intracellular survival." Berlin mbv, 2008. http://d-nb.info/998075302/04.
Full text
39
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.
Full text
40
Willis, Laura B. (Laura Bethg) 1967. "Identification and characterization of novel Rhizobium meliloti genes involved in carbon metabolism." Thesis, Massachusetts Institute of Technology, 1998. http://hdl.handle.net/1721.1/50353.
Full text
41
Watson, Nicola Sophia Alexandra. "Identification of novel genes involved in Paget's disease by Differential Display PCR." Thesis, University of Aberdeen, 1999. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU535579.
Full textAbstract:
In order to identify novel genes which were expressed in Paget's disease, the Differential Display PCR technique was used to compare gene expression in samples of Pagetic and normal bone, and in human bone long term marrow cultures. Several genes appeared to be differentially expressed in Pagetic bone in comparison to controls, however the display patterns were difficult to interpret and consistent differences were not observed. Pagetic marrow cultures were studied and were found to be abnormal in that osteoclast-like cell formation was 20-fold higher in Pagetic marrow than in age-matched controls. This study also examined Pagetic marrow samples aspirated from both affected and unaffected sites, and it was found that large numbers of oseteoclast-like cells formed in Pagetic cultures regardless of the site of marrow aspiration, suggesting that there may be an abnormality in osteoclast precursors in Paget's disease. Differential display of these marrow samples revealed consistent differences in gene expression between Pagetic and normal marrow, and of four differentially expressed mRNAs which were cloned and sequenced, one was selected for further study owing to its significant homology to murine Centrosomin A, a gene thought to be involved in cell cycle division and microtubule formation. The centrosomin-like DD clone was confirmed to be significantly over-expressed in Pagetic marrow by semi-quantiative PCR, and using 232bp DD product as a probe, a ZAP Express osteoclastoma cDNA library was screened by hybridisation to identify cross-hybridising clones. Thirty four positive clones were identified, and two of these clones, CLC 1 and CLC 2, were isolated and sequenced. Database searches identified CLC 2 (4kb) as being a partial clone of human eukaryotic translation initiation factor-3 (eIF-3) - p180 subunit. Further characterisation of both CLC-1 and 2 may provide important information on their functions, both within the cell and their possible role in Paget's disease.
42
Davies, Benjamin. "Serine proteases expressed in the rodent hippocampus : identification of two novel genes." Thesis, University of Edinburgh, 1997. http://hdl.handle.net/1842/13583.
Full textAbstract:
Serine proteases in the central nervous system modulate developmental and synaptic plasticity and are implicated in the pathophysiology of Alzheimer's disease. This thesis aims to characterise the spectrum of serine proteases expressed in the brain. Degenerate primers were designed from regions conserved among the major chymotrypsin clan of serine proteases; these were used for the polymerase chain reaction amplification of family members represented in cDNA form adult rat hippocampus. 10 different members of the family were uncovered. The most abundant products corresponded to tissue plasminogen activator (t-PA) and RNK-Met-1, a lymphocyte protease not previously reported in brain. Evidence is provided to suggest that the major t-PA substrate, plasminogen, is absent from brain, arguing that the target for t-PA in brain is unlikely to be plasminogen, Other enzymes represented include elastase IV, proteinase3, complement C2, Hageman factor, chymotrypsin B, chymotrypsin-like protein and two novel family members, BSP-1 (brain serine protease-1) and BSP-2. Full length sequences of BSP-1 and BSP-2 are reported and sequence motifs and homologies suggest they represent trypsin-like proteases. The expression patterns for each of the serine proteases amplified, as determined by Northern and in-situ hybridization analysis, are presented. BSP-2 is expressed in the hippocampus and the cerebral cortex whereas BSP-1 is confined in its expression to the CA fields of the hippocampus. A gene restricted in expression to the hippocampus has considerable potential for transgenic experimentation into the role of this brain region. Directing expression of suitably modified components of the synaptic signalling pathway within this brain region would allow the relationship between hippocampal synaptic plasticity and learning and memory events to be assessed. To investigate the feasibility of such an approach, the murine BSP-1 locus has been targeted with an IRES-lacZ reporter cassette. Preliminary results indicate reporter expression is active from the murine BSP-1 locus.
43
Babbs, Christian. "Identification and characterisation of novel genes involved in mouse early inner ear development." Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393425.
Full text
44
Besi, Maria. "Identification of novel pathogenicity-related genes in the rice blast fungus, Magnaporthe oryzae." Thesis, University of East Anglia, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.539361.
Full text
45
Song, Yang, and 宋揚. "Identification of the novel genes during endochondral ossification in the mandibular condylar cartilage." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43085568.
Full text
46
Ethirajan, Lakshmi Priya. "Identification and analysis of novel de-regulated genes/proteins in human carotid atherosclerosis." Thesis, Manchester Metropolitan University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.440238.
Full text
47
Shaw, Lesley E. "The identification of novel genes associated with endocrine resistance in human breast cancer." Thesis, University of Reading, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408985.
Full text
48
Song, Yang. "Identification of the novel genes during endochondral ossification in the mandibular condylar cartilage." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43085568.
Full text
49
Joshi, Shreyas. "IDENTIFICATION OF NOVEL SLEEP RELATED GENES FROM LARGE SCALE PHENOTYPING EXPERIMENTS IN MICE." UKnowledge, 2017. http://uknowledge.uky.edu/biology_etds/42.
Full textAbstract:
Humans spend a third of their lives sleeping but very little is known about the physiological and genetic mechanisms controlling sleep. Increased data from sleep phenotyping studies in mouse and other species, genetic crosses, and gene expression databases can all help improve our understanding of the process. Here, we present analysis of our own sleep data from the large-scale phenotyping program at The Jackson Laboratory (JAX), to identify the best gene candidates and phenotype predictors for influencing sleep traits.
The original knockout mouse project (KOMP) was a worldwide collaborative effort to produce embryonic stem (ES) cell lines with one of mouse’s 21,000 protein coding genes knocked out. The objective of KOMP2 is to phenotype as many as of these lines as feasible, with each mouse studied over a ten-week period (www.mousephenotype.org). The phenotyping for sleep behavior is done using our non-invasive Piezo system for mouse activity monitoring. Thus far, sleep behavior has been recorded in more than 6000 mice representing 343 knockout lines and nearly 2000 control mice. Control and KO mice have been compared using multivariate statistical approaches to identify genes that exhibit significant effects on sleep variables from Piezo data. Using these statistical approaches, significant genes affecting sleep have been identified. Genes affecting sleep in a specific sex and that specifically affect sleep during daytime and/or night have also been identified and reported.
The KOMP2 consists of a broad-based phenotyping pipeline that consists of collection of physiological and biochemical parameters through a variety of assays. Mice enter the pipeline at 4 weeks of age and leave at 18 weeks. Currently, the IMPC (International Mouse Phenotyping Consortium) database consists of more than 33 million observations. Our final dataset prepared by extracting biological sample data for whom sleep recordings are available consists of nearly 1.5 million observations from multitude of phenotyping assays. Through big data analytics and sophisticated machine learning approaches, we have been able to identify predictor phenotypes that affect sleep in mice. The phenotypes thus identified can play a key role in developing our understanding of mechanism of sleep regulation.
50
Wong, Frances. "Analysis of genes involved in gonadal development : identification of novel sex determination candidates." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/27706.
Full textAbstract:
Genetic and developmental studies have shown that upon the presence or absence of the Y-linked sex-determining gene SRY, the bipotential gonad will develop either as a testis or ovary. Since the discovery of SRY, several other genes (such as WT1, SF1, DAX1 and SOX9) have been isolated which play an important role in gonadal development and sex determination. Despite these advances our understanding of the mammalian sex determination process remains incomplete. To identify new genes involved in gonadal development, a differential screen using Affymetrix GeneChip arrays was performed. Wild-type male and female gonads were dissected from mouse embryos at El2.5 (during the differentiation process) and subjected to microarray analysis. From this extensive analysis, several novel transcripts were identified, which show a sex-specific expression pattern. The validity of this approach was verified by analysing the expression of these novel transcripts by in-situ hybridisation in male and female gonads at E12.5. Transcripts with a confirmed sex-specific expression pattern where then selected for detailed insitu hybridisation of male and female gonads at El 1.5, E13.5 and E14.5. Moreover, real-time PCR of these candidates was carried out to establish a sex-specific gene expression profile during gonadal development, ranging from 17 to 36 tail somites. This thesis also describes the novel approach of applying small interfering RNAs (siRNAs) to a gonadal organ culture system. Several known sex determination genes were successfully targeted and knocked-down by applying this technique. Importantly, siRNA against Sry effectively blocked male gonad differentiation resulting in a lack of expression of male specific markers. Taken together these results suggest that the siRNA approach in gonad cultures can be used to efficiently analyse the function of candidate genes isolated in our sex determination screen.