Obiettivi

Eukaryotic cells rely for their correct morphogenesis on the timely and spatially regulated transport of proteins and membranes along intracellular trafficking routes. Neurodegeneration, synaptic transmission as well as abnormal cell proliferation can arise when this coordination is altered.

In our group we use different genomic strategies applied to cancer, neuronal and yeast cellular models to identify molecular markers and clarify the basis of pathologies caused by defects in intracellular trafficking and cell proliferation.

The potential of high-content high-throughput microscopy in drug discovery, diagnostics and anticancer therapy

We have recently set up a High content screening (HCS)-based image facility.
We are equipped with a ScanR Olympus Microscopy Station for High Content Screening and Analysis, in addition to a Freedom EVO150 automatic robotic station for sample handling.

HCS is becoming an important and widely-used research tool to screen libraries of small molecules and conventional drugs for their efficacy in reverting pathological phenotypes at a cell-based level.
High Content image Analysis (HCA) allows the rapid assessment of key cellular pathways by analyzing large number of cells in quantitative manner for their response to exogenous and intracellular stimuli. Large panels of compounds/siRNAs can be studied in a single HCS assay and multiple cellular parameters can be analyzed simultaneously.
Among the parameters that can be measured are neurite outgrowth, cell shape and proliferation, transport efficiency, phosphorylation state of given markers, cytoskeletal defects, stage of the cell cycle, nuclear morphology, apoptosis and ploidy, mitotic spindle structures, motility etc.
At the moment several groups within and outside the CMNS are users of the HCS Facility and we are helping them to set-up their favorite cell-based assay suitable for HCS and HCA studies.

In my group we currently use HCS technology to clarify the mode-of-action of anticancer compounds of clinical interest and to clarify the function of genes involved in monogenetic diseases caused by intracellular traffic defects. These projects are currently financed by AIRC and Telethon foundation.