A deep understanding of ttie physiology and biophysics of fusion - and its disease relevance - requires a broad and comprehensive approach and relies heavily upon interdisciplinary approaches honed from a decade of studies of the mechanism of viral envelope fusion. These technologies - cell and molecular biology, surface force/adhesion biophysics, and optical imaging.
The specific aims ofthe initial application covered four aspects of SNARE induced fusion: 1) SNARE distribution, mobility, and lateral interactions within the plane ofthe membrane. 2) Adhesive and molecular forces between SNAREs - determinants of transition states and the energetic. 3) Penultimate states of SNARE fusion: capturing the SNAREpin just before lipid-mixing, with a specific focus on the interplay between lipid structure and protein assembly. 4) Protein and lipidic determinants of fusion kinetics and pore formation.

Public Health Relevance

This broad and comprehensive approach to elucidating the mechanism of intracellular membrane fusion by SNARE proteins will deepen our understanding ofthe physiology and biophysics effusion - and its key roles in diabetes.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (NSS)
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Haft, Carol R
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Yale University
Anatomy/Cell Biology
Schools of Medicine
New Haven
United States
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Bello, Oscar D; Auclair, Sarah M; Rothman, James E et al. (2016) Using ApoE Nanolipoprotein Particles To Analyze SNARE-Induced Fusion Pores. Langmuir 32:3015-23
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