McHattie, Stuart (2011) Modelling transcriptional networks in plant senescence. PhD thesis, University of Warwick.

Preview

PDF WRAP_THESIS_McHattie_2011.pdf - Submitted Version - Requires a PDF viewer. Download (45Mb)

Request Changes to record.

Abstract

Senescence is a highly regulated developmental process in plants in which nutrients are
remobilised from organs which are no longer required or are stressed so that they may be
used by organs which are only just developing. Whilst much is known about the causes
of and the resulting outcomes of this process, very little is known about the genetic
machinery which link them. Some genes have been identified as having a regulatory
role in the senescence process, but many of these have been determined by a forward
genetics approach whereby mutants are randomly screened for phenotypical e↵ects. A
much better approach, where possible, is the reverse genetics approach whereby mutants
are sought for testing as they are suspected to demonstrate a phenotypical e↵ect.
It was the purpose of this study to find novel ways of identifying those genes
which may be highly regulatory of the senescence process and to determine how they are
able to lead from several di↵erent known causes of senescence through to the senescence
response itself. It was hypothesised that, using measurements of the expression levels of
a very large number of genes throughout the senescence process, theoretical models of
regulation between those genes could be determined and that these theoretical models
would allow specific interactions to be identified and explained using biological validation
techniques.
A large microarray experiment, performed prior to the start of this project,
measured the expression of over 30,000 genes in the Arabidopsis thaliana genome over
a period of 21 days during natural senescence. By cleaning this data and fitting an
ANOVA driven model to the resulting intensity measurements, it has been possible
to separate e↵ects leading to observed expression changes. The levels of each of these
e↵ects were tested by F-tests and this has allowed the identification of 8,878 genes which
are significantly di↵erentially expressed during senescence.
By first using theoretical models to find genes amongst the set of 8,878 which
demonstrate highly robust regulatory behaviour on other genes in the set, 118 genes were
able to be isolated for further study. A senescence phenotype screen was developed to
assess reduced-expression mutants of many of those 118 genes and 8 were shown to
have a significantly altered timing of senescence when compared with wild-type plants.
The surrounding networks of each of those 8 genes were formed by applying theoretical
regulatory network modelling in another novel manner similar to a Metropolis-Hastings
approach which identified a set of 75 genes providing a testable regulatory network
model.
The resulting network model has been tested biologically to establish the accuracy
of the predictions. Whilst many of the predictions were not confirmed, a vast
network has been identified surrounding two of the highly regulatory genes indicating a
junction of two separate pathways leading to the senescence response and providing a
network structure which could be used in another round of theory and validation. Additionally,
these results introduce new interesting questions about how the senescence
network may have evolved to respond to so many inputs.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QK Botany
Library of Congress Subject Headings (LCSH):	Arabidopsis thaliana -- Genetics, Plant genetics, Genetic transcription
Official Date:	August 2011
Dates:	Date Event August 2011 Submitted
Institution:	University of Warwick
Theses Department:	Systems Biology Doctoral Training Centre
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Buchanan-Wollaston, Vicky ; Wild, David ; Mead, Andrew
Extent:	xviii, 319 [31] p. : ill., charts
Language:	eng

Request changes or add full text files to a record

Repository staff actions (login required)

View Item

Downloads