Neuropathic pain is a significant worldwide health problem that is poorly understood and often untreatable. A major factor in the pathogenesis of neuropathic pain is an activation of microglial cells in the spinal cord. Following damage to peripheral nerves, these activated cells release factors that increase excitability in spinal pain circuitry. Using expression profiling studies of microglial cells the host laboratory discovered a putative chloride channel transcript that is highly upregulated in these cells: Anoctamin-6 (Ano6). Although the functions of chloride currents in microglia are already known the underlying molecular entity of these currents is not known. The aims of this project are twofold. Firstly I will continue with expression profiling of microglia in a mouse model of neuropathic pain. Secondly I will perform a full characterization of Ano6. Initially I will analyze its activation mechanisms and pore properties in heterologous cells. Subsequently, I will examine its function in vivo using a mouse knockout model, determining its involvement in microglial physiology and in neuropathic pain. Results originated in this study will contribute to a better understanding of neuron-microglia communication in neuropathic states with the possibility to further uncover novel targets for treating human neuropathic pain. EMBL Monterotondo would offer me the possibility to gain specific skills in molecular biology, electrophysiology and in vivo mouse genetics thanks to the on-site Core Facilities and to the collaboration with EMBL Heidelberg and La Sapienza Rome. The skills acquired will greatly benefit my scientific career leading to maturity and independence, allowing me to interact with many research fields and to use powerful tools. Collaborations with other research groups will also improve my independent thinking. Finally, such a research experience would facilitate the ultimate achievement of an independent leading position in the Neuroimmunology research