Mucus functions as the first line of defence against infections, amongst other roles. The protective role of mucus depends upon gel-forming properties of mucin molecules that are encoded by the MUC genes. Failure of this protective barrier has been associated with changes in structure, function and physical properties of mucins in human diseases (cancer, IBD and cystic fibrosis) and has been proposed as a prognostic tool for early diagnosis of these diseases. The study of coral mucus is in its infancy and early investigations on coral mucus gave incomplete and variable chemical composition data. The dynamic nature of the coral surface mucus layer (SML) in limiting pathogens remains unexplored. The present study attempts to detect coral muc genes by tracing the evolution of muc genes from cnidarians to mammals using bioinformatics tools, examines the coral mucin molecule and investigates the response of epidermal and surface mucus to the changing environmental conditions. The presence of a continuous SML at least 145 μm thick on the coral epithelium has been demonstrated for the first time. Rheological studies confirmed the presence of high molecular weight, polymeric glycoprotein similar to mammalian mucin. The study has also developed molecular tools (primers) based on bioinformatics information and has detected tandem repeats rich in serine, threonine and proline and C-terminal Cysteine Knot regions homologous to those of human gel forming mucins. A variation in the epidermal mucus content as well as SML was noticed in between the species as a response to bleaching (loss of zooxanthellae and complete white appearance of coral tissue) and changing environmental conditions (tidal cycle). Thus, study of mucus indicates the health of corals and plays an important role in survival of coral during diseases and environmental stressful conditions.

The lysosomal system of the hepatopancreatic digestive cell of the mussel (Mytilus sp.) is critical in intracellular food degradation, toxic responses and internal cellular turnover. Mathematical and numerical models are developed to simulate the responses of this system to varying conditions, dietary and toxicological. The model evolution encompasses: inclusion of glycogen/lipid storage forms; extrapolation to include nitrogen metabolism; development of rate of endocytosis and food signal; increased functionality of endo/lysosomes; shift to protein/carbohydrate/lipid based model; and the incorporation of the cost of normal Sanction and replacement of damaged components. Control is asserted through control of cytosolic concentrations: the intial assumption of constant carbon concentration is shown to be unacceptable for later models. A control algorithm is developed which regulates cell volume by the ratio of proteinaceous material to energy forms. Endocytosis is shown to be the main determinant behind routine cellular behaviour. Observed phasic behaviour of the digestive tubules is incorporated into the cellular behavioural pattern. A probability-based model for the rate of endocytosis is developed. Increased autophagy as the sole response to toxic injury is found to be inadequate to explain observed responses. It is proposed to complement this response with impairment of lysosomal efficiency to explain this inadequacy. Toxic injury is implemented through an increase in the rates of damage to cellular components. Within the lysosome this leads to a reduction in the concentration of digestive enzymes inhibiting lysosomal performance and, in conjunction with the enhanced autophagy due to increased cytosolic damage, invoking the lysosomal swelling commonly observed.

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Contemporary theories of animal learning propose that memory for a specific event can be based upon either an elemental network of associations, a configural associative network or a hybrid of these possibilities. The two aims of this thesis were (1) to assess whether rats form configural representations of the spatiotemporal features of specific cues, and (2) to test the hypothesis that the hippocampus plays a critical role in configural representations that encode the spatiotemporal properties of an event, more commonly known as episodic memory. Chapter 2 investigated rats' ability to represent the spatiotemporal context in which objects were presented. These experiments failed to find robust evidence for such an ability. Chapter 3 discusses the development of a novel task, based on a sensory preconditioning procedure, that demonstrated configural memory for the spatiotemporal features of auditory cues in normal rats. In addition, it was shown that excitotoxic lesions of the hippocampus disrupted such configural memories. The experiments reported in Chapter 4 used the procedure developed in Chapter 3 to show that temporary inactivation of the hippocampus during memory retrieval disrupted configural, but not elemental memory retrieval. The results presented in this thesis support the hypothesis that normal rats are able to form elemental and configural representations involving the spatiotemporal properties of cues, and that the hippocampus has a role in configural but not elemental associative memory.

Dictyostelium discoideum is a eukaryotic amoeba that has proven to be an excellent model system for the study of chemotaxis and development. Upon starvation, individual amoebae are able to aggregate and undergo development to form a fruiting body. Previously it has been demonstrated that this process is disrupted by two drugs commonly used to treat bipolar disorder, lithium and valproic acid (VPA) and in this study I show that this disruption is due to the inhibition of cell movement. Previous work has shown that ablation of the gene encoding prolyl oligopeptidase (PO) is able to confer resistance this effect. Both drugs have the common property of depleting intracellular inositol levels, and the observation that PO null cells have increased production of inositol 1,4,5 trisphosphate (Ins(1,4,5)P3) from the dephosphorylation of InsP5 therefore suggests that this activity may be responsible for lithium resistance. In this study I have cloned, and generated mutants of, the gene encoding this inositol phosphatase activity and shown that it is essential for lithium resistance in PO null cells and that this resistance is due to upregulated transcription of the lithium-sensitive IMPase family of genes. In addition I have shown that cells lacking phospholipase C activity are also lithium resistant, indicating that the recycling of inositol phosphates and lipids plays an important role in maintaining cell movement and lithium action.

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A strain difference was observed in juvenile OD plasticity between C57BL/6J and C57BL/6JOlaHsd mice whereby open eye 'homeostatic' potentiation was completely absent in the C57BL/6JOlaHsd strain. This was accompanied by an absence of dark exposure induced synaptic scaling as measured <italic>ex vivo.</italic> In contrast in adulthood both strains showed comparable open eye potentiation, suggesting a mechanistic difference between juvenile and adult plasticity. Preliminary data suggests that while juvenile open eye potentiation is homeostatic, in adulthood it may be more LTP like and dependent upon CaMKII autophosphorylation.

Muscle differentiation is a complex process involving the transition from undifferentiated mesoderm to a final functional musculature. Mef2 is an essential positive regulator central to the co-ordination of this process. It targets a plethora of key genes both early and late in the differentiation program and its activity must be tightly controlled (Pothoff and Olson, 2007). The aim of my research was to investigate the role of Mef2 in orchestrating Drosophila muscle differentiation. I did this by analysing the formation of the larval somatic musculature under conditions that either increased or decreased Mef2 activity using gain and loss-of -function of either Mef2 itself, Him, a repressor of Mef2 activity (Liotta et al, 2007) or of Zfhl, a potential regulator of Mef2 expression (Postigo et al, 1999). Part of this investigation involved the generation and characterisation of Mef2 dominant negative proteins and isolation of a Him mutant. Detailed analysis revealed a distinct subset of somatic muscles that are missing when Mef2 activity is reduced and another subset of muscles that are duplicated when Mef2 activity is increased. This suggests a role for Mef2 in patterning of the musculature that has not been established previously. In addition, I identified a role for Mef2 in the regulation of Him expression, revealing a mechanism whereby Mef2 could be involved in its own repression. I also investigated the role of mesol8E in muscle differentiation a previously uncharacterised novel gene identified as an early target of Mef2 (Taylor, 2000). I found this to be a Myb-like domain containing protein that is a direct target of Mef2. Over-expression caused a severe disruption to the somatic musculature, revealing a potential role for mesol8E in muscle guidance. Generation of mesol8E mutant alleles by FRT element mediated recombination showed the gene to be essential for development.