Multimodal Delineation of Neurodegenerative Mechanisms

项目总结

PROJECT SUMMARY The goal of this proposal is to train the next generation of scientists that will advance our understanding of Alzheimer’s Disease and Related Dementias (ADRD) at Yale University, and to fulfil the promise of developing disease-modifying therapeutics for these debilitating conditions. The rationale of this program is to take an integrated approach to understand the diversity and similarities of ADRD conditions as well as their co-morbidity, using cell biology, structural biology, pathology, biostatistics, and clinical medicine. Twenty nine (29) faculty from twelve (12) basic and clinical departments at Yale School of Medicine and Yale College are participants in this multidisciplinary program. The program offers both depth and breadth. The depth derives from the expertise of the faculty investigating ADRDs and the many institutional resources that can be brought to bear including, an Alzheimer’s Disease Research Center (ADRC), a Parkinson’s Foundation Research Center, three Aligning Science Across Parkinson’s (ASAP) teams, a recently instituted Center for Human Brain Discovery brain bank, and a new research building where most mentors will co-locate. The breadth of the program derives from the diversity of approaches being used to tackle these diseases ranging from genetics to drug development. Mentors are Ph.Ds. and M.D.s. with substantial NIH support and NIA/NINDS related research foci. Faculty investigate all major forms of dementia, including Alzheimer’s disease (AD), Frontotemporal Dementia (FTLD), Lewy Body Dementia (LBD), and Vascular contributions to cognitive impairment and dementia (VCID). Methodologies include deep sequencing; transcriptomics; proteomics; cell and induced pluripotent stem cell (iPSC) culture; immunohistochemistry; electron and advanced light microscopy; biochemistry and molecular analyses; structural biology; rodent, monkey behavior; and fMRI and PET imaging in human subjects. Six predoctoral positions are requested. Trainees are selected by the Executive Committee from an outstanding pool of advanced Neuroscience and Biology graduate students (3rd and 4th year), which are amongst the best in the country and come from a variety of backgrounds in the sciences. Trainees are selected based on their potential for excellence, leadership in research as well as their diverse backgrounds. Training includes focused coursework, instruction in experimental design and statistical methods, Clinicopathologic correlation (CPC) conferences, thoughtful mentorship through advisory committees with oral and written feedback, structured seminar programs, career skills development, and numerous opportunities for written and oral presentation of research progress.