PINNEH, ELIZABETH,CASSANDRA (2018) Targeting a promising new herbicide mode of action: chemical and genetic approaches to elucidate the role of IPC synthase in plants. Doctoral thesis, Durham University.
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Author-imposed embargo until 30 May 2021.
Worldwide there are currently 479 recorded unique cases of herbicide resistant weeds, with 251 species (146 dicots and 105 monocots). According to current records, weeds have developed resistance to 22 of the 25 known herbicide sites of action and to 157 different herbicides. Research into sphingolipid synthesis has revealed a potential novel site of action involving the non-mammalian enzyme inositol phosphorylceramide synthase (IPCS). Two approaches to understanding the function of the enzyme in plants have been employed in this study. The genetic approach, which involves the overexpression and knockdown of the three IPCS orthologues in Arabidopsis thaliana, has given insights into the global function of the enzyme in plants at a phenotypic and transcriptomic level. Analyses of the RNASeq data show that AtIPCS is a global negative regulator of plant defense, downregulating genes involved in plant defense against herbivory attack, nematodes, fungal and bacterial pathogens. RNASeq data in conjunction with phenotypic data, indicate that IPCS may play a role in floral transition from the vegetative phase to the reproductive phase, with the transgenic lines displaying an early flowering phenotype. AtIPCS transcript levels is also shown to affect plant post-embryonic development. In parallel, high throughput screening facilitated the identification of chemical inhibitors of plant IPCS. Using a system of Arabidopsis thaliana as a model dicot and Oryza sativa as model monocot, two classes of inhibitors were identified and demonstrated differential activity: the phenylamidines and triazinones. In addition, in vivo screening of the phenylamidines demonstrated herbicidal activity, indicating that the necessary selectivity for herbicide development is achievable.
|Item Type:||Thesis (Doctoral)|
|Award:||Doctor of Philosophy|
|Keywords:||Inositol phosphorylceramide synthase, Arabidopsis thaliana, High throughput screen, small molecule inhibitors, RNASeq, plant defense, early flowering, abiotic stress, post-embryonic development|
|Faculty and Department:||Faculty of Science > Chemistry, Department of|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||06 Jun 2018 11:04|