My research is focused on altered endosome-lysosome biogenesis in immune and mental retardation disorders. These two project areas are linked by commonality in the endosome-lysosome cell biology and related pathogenesis. For example, the current research focus on innate immune antimicrobial peptide secretion involves similar molecular mechanism to neurotransmission. Moreover, many aspects of neuropathology involve inflammation, which is becoming very evident in, for example, lysosomal storage disorder patients. The specific objectives of my research are to: Define the molecular mechanism of innate immune secretion; Devise a strategy to enable the innate immune system to eradicate H. pylori; Determine the critical link between lysosomal storage and altered neurotransmission; Develop therapeutic strategies to address mental retardation. Background: Endosomes are membrane bound compartments within eukaryotic cells and can be formed by cell surface invagination, for example during the endocytosis of macromolecules for delivery to lysosomes for degradation. Lysosomes were first described by De Duve in 1955, as acidic organelles containing an array of degradative hydrolases; a discovery that was linked with the primary dysfunction observed in lysosomal storage disorder patients. Endosomes and lysosomes are contiguous with the cell surface and therefore form a functional interface between the cell and its environment. This critical set of organelles is now recognised as having functions in macromolecular degradation, organelle turnover, cellular recycling, energy pathways, phagocytosis, pathogen killing, antigen presentation and immunity, signalling, cell membrane repair, cell division, intracellular transport, secretion and neurotransmission. Any dysfunction in endosome-lysosome organelles will therefore potentially impact on these important cellular functions. The capacity of this organelle system to respond to environmental change may act as an indicator of cellular function and disease and be altered as a result of the specific disease process. Hypotheses: Altered endosome-lysosome biogenesis is integrally involved in inflammatory and mental retardation disorders. This involvement occurs due to either a primary mutation that alters endosome-lysosome function or as part of a cellular response to another disease process
