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Research Activities in the
Life Sciences

- Neuroscience

- Cell & Molecular Biology of Plant

- Molecular Entomology
- Enzyme Structure & Function
- Vertebrate Embryonic Development
- Insect & Plant Pathology
- Clinical Pharmacology
- Pharmaceutical Biology
- Pharmaceutical Technology

Nicotinic receptors in the brain are the site of action of doses of nicotine encountered during tobacco smoking and mediate the psychoactive and addictive properties of the drug. Many of these nicotinic receptors appear to be located on presynaptic elements, where they can positively modulate transmitter release. TEM and immunocytochemistry are being used to study presynaptic nicotinic receptor structure and function.
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Studies to further the understanding of genomic imprinting in Arabidopsis involve interploidy crosses that show reciprocal developmental effects in the seed caused by parental genomic excess. TEM is being used to study the ultrastructure of the developing seed endosperm following a variety of interploidy crosses.
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Insecticide resistance is one of the most frequently cited examples of natural selection. Associated with insecticide resistance is the study of novel insecticidal toxins for use in resistance management strategies for transgenic plants. Current work is focused on four toxin complexes cloned from the bacterium Photorhabdus luminescens. The bacterium is symbiotic with nematodes that invade insects and is released into parasitised insects following invasion of the nematode. The bacteria replicate quickly killing the insect and facilitating nematode reproduction. The toxins have been purified, antibodies raised against them and the genes that encode them cloned. Genetic deletion of these genes shows two of them are largely responsible for oral toxicity against Lepidoptera. Current studies involving functional expression of the toxins and toxin mode of action are using TEM and immunocytochemistry to learn more about these toxic proteins.
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Xanthine oxidase (XO) is a complex enzyme with the capacity to generate reactive oxygen species (ROS) implemented in a range of diseases (heart attack, stroke and arthritis). It can also catalyze the reduction of nitrates and nitrites to nitric oxide (NO), an important signalling molecule and potentially destructive agent. It has been proposed that XO, abundant in milk, serves to sterilize the neonatal gut by way of NO production. Antibodies have been generated using highly purified human XO and are being used to determine the intracellular distribution of the enzyme in cultured endothelial and epithelial cells by TEM immunocytochemistry.
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Together with tissue culture, confocal microscopy and molecular techniques TEM is being used to investigate the cell lineage of the pancreas. Of particular interest is the origin of endocrine cells, particularly beta cells, and the cause of hepatic metaplasia, a process in which pancreatic cells become converted to a liver phenotype.
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Fungal pathogens used to control insect pests are gradually reducing reliance on synthetic chemical pesticides. The aim of current research is to further the development of efficient mycoinsecticides. As part of ongoing investigations into the mechanisms of fungal invasion of host insects, the techniques of low temperature SEM, TEM and Atomic Force Microscopy are being used.
Studies of the resistance of the cocoa plant Theobroma cacao to verticillium has been linked to the production of four novel natural ‘fungicides’ (phytoalexins) including elemental sulphur. Further research into the distribution and localization of elemental sulphur in various infected plant species is in progress using among other techniques low temperature SEM and X-ray Analysis.
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Investigations into the effects on the gastrointestinal tract of drugs used to treat the major forms of arthritis is being carried out using SEM. This study has produced a method for the successful retrieval and preparation of small bowel biopsies by enteroscopy for SEM. A previously unknown and unusual helical organism has been discovered in the human gut and imaged by SEM.
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Gene therapy emerged in the 1990’s as a possible method of treatment for cancer. It involves direct delivery of DNA plasmids into the nucleus of particular cells. Research in this area aims to produce synthetic virus-like particles with the attributes of viruses and prepared by self-assembly of supramolecular complexes. The particles are designed to make use of active transport systems in cells to aid delivery of the plasmids to the nucleus. Among other techniques TEM, immunocytochemistry and AFM are being used to investigate this process.
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The design and dosage forms which deliver accurately metered doses of drugs to precise locations in the human body requires that each compound of the delivery system is well characterised. Several types of dosage form are under study, in particular: Dry powder inhalers, tablet excipients for conventional and controlled release and coating systems for tablets. Also being studied is the effect on dosage forms of manufacturing processes – how interactions between particles or materials in liquid, semi-solid or solid phases in simple and complex dosage forms can be manipulated to improve dosage form and manufacturing process. The SEM and its low temperature instrumentation for studying hydrated materials is an essential facility in this type of research.
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