This thesis is concerned with the study of a Bayesian clustering algorithm, proposed by Heard et al. (2006), used successfully for microarray experiments over time. It focuses not only on the development of new ways of setting hyperparameters so that inferences both reflect the …
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The myeloproliferative disorders (MPDs) are a group of haematopoietic stem cell diseases, characterised by proliferation of one or more cells of the myeloid lineage. Several lines of evidence have highlighted the importance of aberrant tyrosine kinase signalling in the pathogene…
The components that are central to cellular processing are proteins, whose production is regulated by other proteins known as transcription factors. Proteins are products of genes that regulate the expression of one another, thereby forming large gene regulatory networks that pe…
Interleukin 6 (IL6) is associated with arterial disease development, progression and surgical outcome. Raised levels of IL6 may play a causal role in disease development or may be the effect of pathology. An IL6 single nucleotide polymorphism (SNP) G- 174C has been identified an…
The genome of the Trichostrongylid nematode parasite of small ruminants Haemonchus contortus is being sequenced at the Pathogen Sequencing Unit of the Wellcome Trust Sanger Institute, Cambridge, UK. Currently, in excess of 800 Mb of genomic sequence is available for this on-goin…
Synthetic molecules that target the major groove in a sequence-selective way are a major goal in molecular medicine. Recently a major step has been taken toward achieving this goal: a novel cylinder has been developed that binds strongly into the major groove of DNA. Experimenta…
Trypanosoma brucei is an evolutionarily divergent eukaryotic parasite of mammals in sub-Saharan Africa and is transmitted by the tsetse fly vector. To evade the mammalian immune response, T. brucei utilises antigenic variation, which involves switches in the Variant Surface Glyc…
Malaria, caused by infection with intracellular protozoan parasites of the genus Plasmodium, is responsible for 300 to 600 million clinical cases annually (Snow et al., 2005), resulting in the deaths of up to three million people every year (Breman, 2001, Breman et al., 2004). T…
Since the discovery of cell-free fetal DNA in the circulation of pregnant women fetal-specific DNA biomarkers for non-invasive prenatal diagnosis of fetal aneuploidy have been sought. A model system assessing the DNA methylation of placental DNA and adult peripheral leukocyte DN…
Injury to the peripheral nervous system (PNS) stimulates a finely regulated regenerative response that generally leads to some recovery of function. In contrast, the response to injury in the adult mammalian central nervous system (CNS) is abortive and adult CNS neurons do not n…
The stroke-prone spontaneously hypertensive rat (SHRSP) is an inbred model of hypertension. Renal microarrays and functional genomic strategies investigated chromosome 2 candidate hypertension genes, focussing on the oxidative-stress defence gene, glutathione s-transferse mu typ…
The renin angiotensin system is often maninpulated clinically for the treatment of hypertension and heart failure. This pathway is of major clinical importance and it is thus a major target for therapy. The incidence of cardiovascular diseases continues to increase worldwide, hi…
Two conserved protein kinases, Chk1 and Chk2, are activated in response to genotoxic stress and mediate multiple cell cycle checkpoint mechanisms that ensure genomic integrity. The establishment of mitotic checkpoint delay in response to DNA damage or incompletely replicated DNA…
The mitotic cell cycle underlies propagation of eukaryotic cells, continually duplicating and dividing. The past few years have seen major advances in understanding of the regulatory mechanisms that impose on the cell cycle to tightly co-ordinate progression through its individu…
Hodgkin lymphoma (HL) is a malignant lymphoma that is diagnosed mostly in young adults, and is the second most common malignancy to affect this age group. This disease is subdivided into two entities with different aetiologies: classical HL (cHL) (~95% of cases) and nodular lymp…
Rodent hepatic myofibroblasts are susceptible to nerve growth factor-mediated apoptosis through p75 neurotrophin receptor ligation. Hepatic myofibroblast apoptosis is critical to resolution of liver fibrosis. I show that human hepatic myofibroblasts exhibit differential response…
Myzus persicae, more commonly known as green peach aphid, is an important pest in agriculture. Each year it causes great losses to agricultural and horticultural plants. It feeds on sap in the phloem, the main transportation route for plant nutrients. It also transmits more than…