Matches in SemOpenAlex for { <https://semopenalex.org/work/W2464265831> ?p ?o ?g. }
Showing items 1 to 71 of
71
with 100 items per page.
- W2464265831 abstract "Juvenile CLN3 disease is a rare lysosomal storage disease, and the most common cause of neurodegeneration in children. Since the identification of the disease gene (CLN3) in 1995, efforts in various cellular and animal models have led to CLN3 being associated with several cellular pathologies. However, its precise molecular function remains unknown. Furthermore, with only a limited knowledge of disease pathogenesis, there remains a considerable need to identify therapeutic targets in order to accelerate the development of therapies for this prematurely fatal disease. Schizosaccharomyces pombe has proved to be a powerful and accurate model to help elucidate the function of CLN3 by virtue of its evolutionary conserved orthologue, btn1+. To date it has revealed both a new cellular localisation and potential functions for btn1+. The primary aim of this project was therefore to further exploit this fission yeast (btn1∆) model, and use synthetic genetic array analysis (SGAs) to identify genome- wide, genetic interactions of btn1+. It was hypothesised that defining the genetic relationships of btn1+ would provide insight into its molecular role, which in turn could be used to infer CLN3 gene function. It was also hoped that such information could be used to identify therapeutic targets and help refine the focus of future work in higher eukaryotic models. Using such an approach, this thesis provides a considerable step in our understand- ing of the function of btn1+, and by extrapolation CLN3, by suggesting that their function likely converges with various stress response pathways. A comprehensive characterization of the btn1∆ strain revealed numerous phenotypes co-incident with known stress response mutants, suggesting that this strain indeed displays compromised stress signalling which may contribute to disease pathogenesis. This thesis also details a number of therapeutic targets as the genetic manipulation of two highly conserved mitogen activated protein kinase pathways (the cell wall integrity (CWI) pathway and stress associated protein kinase (SAPK) pathway) and the interconnected TOR kinase complexes, are shown to rescue aspects, if not all, of the btn1∆ phenotypes investigated. This is the most successful rescue of disease phenotypes in any model for juvenile CLN3 disease to date." @default.
- W2464265831 created "2016-07-22" @default.
- W2464265831 creator A5087418453 @default.
- W2464265831 date "2016-04-28" @default.
- W2464265831 modified "2023-09-26" @default.
- W2464265831 title "Identification of genetic interactions in a S. pombe yeast model for juvenile CLN3 disease" @default.
- W2464265831 hasPublicationYear "2016" @default.
- W2464265831 type Work @default.
- W2464265831 sameAs 2464265831 @default.
- W2464265831 citedByCount "0" @default.
- W2464265831 crossrefType "dissertation" @default.
- W2464265831 hasAuthorship W2464265831A5087418453 @default.
- W2464265831 hasConcept C104317684 @default.
- W2464265831 hasConcept C116834253 @default.
- W2464265831 hasConcept C127716648 @default.
- W2464265831 hasConcept C14036430 @default.
- W2464265831 hasConcept C142724271 @default.
- W2464265831 hasConcept C19843653 @default.
- W2464265831 hasConcept C2776925932 @default.
- W2464265831 hasConcept C2777576037 @default.
- W2464265831 hasConcept C2779134260 @default.
- W2464265831 hasConcept C2779429346 @default.
- W2464265831 hasConcept C54355233 @default.
- W2464265831 hasConcept C59822182 @default.
- W2464265831 hasConcept C60644358 @default.
- W2464265831 hasConcept C70721500 @default.
- W2464265831 hasConcept C71924100 @default.
- W2464265831 hasConcept C86803240 @default.
- W2464265831 hasConceptScore W2464265831C104317684 @default.
- W2464265831 hasConceptScore W2464265831C116834253 @default.
- W2464265831 hasConceptScore W2464265831C127716648 @default.
- W2464265831 hasConceptScore W2464265831C14036430 @default.
- W2464265831 hasConceptScore W2464265831C142724271 @default.
- W2464265831 hasConceptScore W2464265831C19843653 @default.
- W2464265831 hasConceptScore W2464265831C2776925932 @default.
- W2464265831 hasConceptScore W2464265831C2777576037 @default.
- W2464265831 hasConceptScore W2464265831C2779134260 @default.
- W2464265831 hasConceptScore W2464265831C2779429346 @default.
- W2464265831 hasConceptScore W2464265831C54355233 @default.
- W2464265831 hasConceptScore W2464265831C59822182 @default.
- W2464265831 hasConceptScore W2464265831C60644358 @default.
- W2464265831 hasConceptScore W2464265831C70721500 @default.
- W2464265831 hasConceptScore W2464265831C71924100 @default.
- W2464265831 hasConceptScore W2464265831C86803240 @default.
- W2464265831 hasLocation W24642658311 @default.
- W2464265831 hasOpenAccess W2464265831 @default.
- W2464265831 hasPrimaryLocation W24642658311 @default.
- W2464265831 hasRelatedWork W1498098115 @default.
- W2464265831 hasRelatedWork W1894518482 @default.
- W2464265831 hasRelatedWork W1967319983 @default.
- W2464265831 hasRelatedWork W1982733033 @default.
- W2464265831 hasRelatedWork W1983649458 @default.
- W2464265831 hasRelatedWork W1988834592 @default.
- W2464265831 hasRelatedWork W1991962141 @default.
- W2464265831 hasRelatedWork W1999202099 @default.
- W2464265831 hasRelatedWork W2007701552 @default.
- W2464265831 hasRelatedWork W2026678793 @default.
- W2464265831 hasRelatedWork W2090811090 @default.
- W2464265831 hasRelatedWork W2090839709 @default.
- W2464265831 hasRelatedWork W2098810561 @default.
- W2464265831 hasRelatedWork W2104425882 @default.
- W2464265831 hasRelatedWork W2113546943 @default.
- W2464265831 hasRelatedWork W2118734144 @default.
- W2464265831 hasRelatedWork W2141531180 @default.
- W2464265831 hasRelatedWork W2164965106 @default.
- W2464265831 hasRelatedWork W2332095084 @default.
- W2464265831 hasRelatedWork W2557248654 @default.
- W2464265831 isParatext "false" @default.
- W2464265831 isRetracted "false" @default.
- W2464265831 magId "2464265831" @default.
- W2464265831 workType "dissertation" @default.