High resolution morphological analysis is an integral part of biological investigations under both physiological and pathological conditions. The fine structure modifications induced during cell motility or cellular secretion are captured in high resolution by transmission electron microscopy (TEM) analysis. Similarly, morphological changes observed in sub-cellular organelles (late endosomes and lysosomes) during various experimental conditions can be powerfully visualized by TEM analysis. Analysis of bacteria and fungi can provide very useful information on their morphological changes under differential experimental conditions. This is a resubmission application for funding of a state of the art high resolution transmission electron microscope and an associated digital camera. The TEM the Major Users of this application are requesting will be part of the Analytical Imaging Facility (AIF, a multi user imaging resource, and available to all trained investigators. Currently, an ageing JEOL JEM-100CX TEM installed 1982 is present in the facility which does not fulfill the needs of these investigators. The common scientific need of the major user in this application is the ability to obtain high resolution imaging of cells, organelles or pathogens under different experimental conditions. A new TEM with a high brightness LaB6 electron source and CCD camera will enable high resolution imaging and digital data recording. The transmission electron microscope described in this proposal will allow the assembled Major Users to analyze pathogen morphology;fine structural aspect of endosomal biogenesis and protein distribution;and granule secretion which will be otherwise precluded.