Project Summary This application requests funding for the 2017 Gordon Research Conference on CAG Triplet Repeat Disorders and the associated Gordon Research Seminar to be held at Mount Snow in West Dover, VT, from June 3-9, 2017. This will be the ninth Gordon Research Conference on CAG Triplet Repeat Disorders. The previous eight have alternated between American (Mount Holyoke College, 2001, 2005; Waterville Valley NH, 2009, 2013) and European (Il Ciocco, Italy 2003, 2011, 2015 and Aussois, France 2007) sites. This is the fifth time that there will be an associated Gordon Research Seminar. The CAG Triplet Repeat Disorders are a group of largely untreatable inherited neurological disorders, which result from an expansion in a CAG trinucleotide repeat in the mutant genes. They include Huntington’s disease (HD), spinal and bulbar muscular atrophy (SBMA, Kennedy’s disease), spinocerebellar ataxias types 1, 2, 3, 6, 7, and 17, and dentatorubropallidoluysian atrophy (DRPLA). In each case, the CAG repeat lies within the coding region of a gene and results in an abnormally long polyglutamine tract in the mutant protein. There are marked similarities both in the underlying genetics and in the neuropathological symptoms, suggesting common pathogenic mechanisms. Exciting new efforts to unravel these mechanisms and to find effective, disease-modifying treatments are under way. Important findings have recently been made in the area of proteostasis research, which is of high relevance to understanding proteopathies, to which the CAG repeat disorders belong. To delineate the networks of cellular homeostasis in their entirety, if possible, ‘-omics’ approaches have moved into the focus and have unraveled surprising new connections between the molecules involved in disease. Seeding and spreading of misfolded protein species have recently been recognized as perhaps highly relevant to pathogenesis. Connected to these phenomena, innovative technologies to identify relevant targets, disease markers and effective therapeutics are in development. To increase the pace of molecular discovery and to reinforce the collaboration between basic and clinical researchers necessary to accelerate translation into the clinic, a multidisciplinary research effort is required. It is essential that exchange of ideas, information and concepts take place so that collaboration between experts in neuro-, molecular and cell biology, biochemistry, pharmacology, network biology, preclinical/clinical research, pathology and technology development is promoted. This conference will gather young investigators and established senior scientists to deliver provoking lectures on the cutting edge of science. In keeping with the Gordon Research Conference format, there will be generous time allocated for both structured discussions led by peers and for informal discussion and social interactions to facilitate collaboration. Strong emphasis is placed on training and mentoring of young scientists, and time will be devoted to career issues. All participants will be required to present posters. Priority will be given to women, minorities and persons with disabilities when selecting participants.

Project Narrative CAG Triplet Repeat Disorders are a group of inherited, neurological diseases, including Huntington’s disease and ataxias, that are largely untreatable and have high medical need. The 2017 Gordon Research Conference on CAG Triplet Repeat Disorders and its associated Gordon Research Seminar will bring together basic and clinical researchers to discuss recent, cutting-edge discoveries on disease mechanisms and therapeutic interventions and to present innovative approaches to investigate, diagnose and treat these devastating diseases. The highly interactive format of the Gordon Research Conference will promote and enhance participation and education of junior scientists, including graduate students, postdoctoral fellows and junior faculty.