Enhancement of olfactory neuron survival and targeting via odorant exposure

作为一名具有丰富嗅觉研究背景和临床经验的耳鼻喉科医生

As an Otolaryngologist with a rich background in olfactory research and experience with the clinical assessment of olfactory disorders, I am positioned with the unique opportunity to combine these two disciplines in the search for medical therapies. This research career development plan consists of five years of mentored training through the design and implementation of the proposed project. Courses in new techniques, statistics, the ethics of animal and human studies, and the responsible conduct of research will supplement this training. The lab of Dr. James Schwob within Tufts University School of Medicine will provide the support, equipment, coursework, and overall educational environment to complete the research and training objectives of this proposal. My long-term career goal is to become an independent investigator within the area of olfaction at the Massachusetts Eye and Ear Infirmary in order to develop effective therapies for patients suffering from olfactory disorders. This research proposal will investigate the hypothesis that directed odorant exposure competitively enhances the survival and axonal targeting of receptor-specific olfactory neurons during recovery from lesion and that this effect occurs at the level of both the olfactory bulbs and olfactory epithelium. The hypothesis will be tested through three specific aims all utilizing the mouse model of recovery from methyl bromide exposure or olfactory nerve transection. Specific Aim 1 will look for the normalization in numbers of several different olfactory receptor subtypes within the epithelium after nares closure and will assess the effect of removing odor-induced activity on axon targeting. Specific Aim 2 will then show that selective repeated odorant exposure provides a competitive advantage in survival and axon targeting for the receptive olfactory neurons. Specific Aim 3 will then demonstrate that the enhanced survival observed in SA2 can occur without the target organ and supports the role of CREB in this process. In summary, this proposal determines the effect of repeated odorant exposure on the recovery of the sense of smell after injury. It provides additional areas of research on the mechanisms of how the system attempts to heal itself, and most importantly, the information gained from this work is relevant for the development of therapies aimed at reversing sense of smell disorders in humans.