TriMED: Measuring, Modeling and Manipulating Excitability and Disease

PROJECT SUMMARY The nervous system is an electrical system, and neurons are the archetypal electrically active cell, but ion transport is fundamental to the regulation of every cell in the body, whether excitable or not, and almost 20% of approved drugs actually work on ion channels. Multiple neurological diseases, including movement disorders, migraine, and epilepsy, can clearly be caused directly by inherited mutations of specific ion channels and transporters, but defective ion transport is also associated with every big disease, from cancers to heart disease to Alzheimer's disease. We aim to generate a cohort of researchers with the appropriate in- depth understanding of membrane biology, in combination with state-of-the-art technical skills, to carry out basic and translational research in excitability. The intended result is researchers with the capability to transform excitability research – and hence therapies – by harnessing burgeoning advances in (i) membrane protein structure determination, (ii) measurement of excitability, by electrophysiology and imaging, from molecular to tissue levels, (iii) modeling, both biological and computational and (iv) modulation of excitability, both pharmacologically and physically. The program will support later stage pre-doctoral and post-doctoral trainees in dual-mentored research, with a primary mentor from one of the above fundamental focus areas, and a second mentor who could be from an applied focus area – including methods development or organismal and clinical studies. In addition to intensive research experiences, trainees will participate in a didactic course, geared towards in-depth research understanding, as well as activities devoted to training in grant writing, presentations, and career development. The program faculty mentors, chosen with regard to breadth and diversity of background and career stage, all with strong track records of funding and commitment to trainee development, the interdisciplinary nature of training opportunities, and institutional commitments combine to foster a unique environment suited to the goal of this TriMED program. The program will identify individuals with appropriate backgrounds, who are committed to a career in excitability research, and provide them with mentored pre- and post-doctoral research experiences that will establish a foundation for future careers capable of bringing new insights and tools to bear in neuroscience and disorders of excitability.