QTL mapping with segregating populations results in poor map resolution which limits the applicability of mapped QTL in further research such as gene cloning. The current research project aimed mainly at developing STepped Aligned Recombinant Inbred Strains (STAIRS) covering the…
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Placental growth factor (PlGF) is a pro-angiogenic and inflammatory mediator that promotes many pathological conditions including, diabetes, atherosclerosis and cancer. In mouse models, the loss of PlGF or inhibition of vascular endothelial growth factor receptor-1 (VEGFR-1) act…
Transcriptional regulation of genes is fundamental to all living organisms. The spatial, temporal and condition-specific expression levels of genes are in part determined by inherited regulatory codes in non-coding regions of the DNA. A large set of methods have been proposed to…
Crop wild relatives have been identified as ecologically and economically important plant genetic resources but are often a neglected resource. The recognition of the need for their specific conservation and their value for future use has been strengthened by the Convention on B…
Neuronal dysfunction and cell death occurs during neurodegeneration. Animal models that express human disease genes and show neurodegenerative-like pathologies are widely used to study particular molecular systems in early neurodegenerative changes. Axonal transport (AT) is pert…
The indiscriminate action of reactive oxygen species (ROS), if left unregulated, has long been considered contributory to a range of disease processes within the animal kingdom and is also a factor associated with ageing. Consequently modifying the molecular mechanisms that regu…
In a rat model of intrauterine growth restriction (IUGR) induced by maternal global undernutrition, adult offspring are obese with associated metabolic disturbances. These metabolic abnormalities are all augmented by feeding a high calorie postnatal diet and reversed by neonatal…
Hypertension is a common, highly heritable trait of complex aetiology. Multiple environmental and lifestyle factors contribute to blood pressure variation. Hence the study of hypertension causality is not straightforward. Genetic linkage studies have implicated a number of loci …
Trypanosoma brucei is the causative agent of both sleeping sickness in humans and the related veterinary disease, Nagana. Both diseases have a wide distribution across sub-Saharan Africa and affect some of the poorest areas of the world. T. brucei can be segregated into three mo…
Micro-RNAs (miRNAs) are a class of non-coding RNA which post-transcriptionally regulate gene expression. Epstein-Barr Virus (EBV) transforms resting B-cells in vitro to establish continuously proliferating lymphoblastoid cell lines (LCLs) and is aetiologically linked to lymphoma…
Sporophytic self-incompatibility is a genetically controlled inbreeding prevention mechanism, which is prevalent in the Brassicaceae, and has been reported in a variety of high profile species. Despite the benefits of preventing self-fertilization in terms of maintaining genetic…
The peptide hormone, ghrelin, exerts its physiological effects through a G-protein-coupled receptor called the ghrelin-R. The ghrelin-R displays a high degree of constitutive activity, signalling through the inositol phosphate pathway in the absence of bound agonist. TMs III and…
The insect Malpighian tubule is involved in osmoregulation, detoxification and immune function, physiological processes which are essential for insect development and survival. As the Malpighian tubules contain many ion channels and transporters, they could be an effective tissu…
The Xenopus pronephros is a simple paired organ; each nephron consists of a single large glomus, one set of tubules and a single duct. Previous work done in our laboratory demonstrates that the tubules and duct are specified at stages 12.5 and 14 respectively and the glomus is s…
Corticotrophin releasing hormone (CRH) and CRH receptor (CRH-R) appear to play a number of important roles in human pregnancy. The purpose of the first part of my project was to clone and sequence CRH-R subtypes from human myometrial biopsies. In order to understand the molecula…
Several genes, essential for cell growth and division in Escherichia coli, have been mapped to the 76 minute region of the chromosome. DNA sequencing of part of this region revealed three cell division genes (ftsY, ftsE, and ftsX) in a putative operon. A fourth gene (orf4) was a…
This thesis presents the modelling and analysis of an engineered genetic oscillator in E.coli. Genetic oscillators composed of transcriptional feedback loops are the central components of circadian clocks [16]. Thus understanding small genetic oscillators is key for understandin…
Two new transcription factor binding sites have been identified within the phosphoglycerate kinase (PGK) gene promoter in the yeast Saccharomyces cerevisiae. The binding sites are upstream of the previously defined UAS, and are bound in vitro by the multifunctional transcription…
The nucleus of the eukaryotic cell contains a large pool of lipids together with structural proteins and genomic DNA. The project aim was to develop simple and robust lipid and DNA models that will allow for these complex molecules to be mixed together in order to elucidate the …