The ACS North Jersey Section is soliciting nominations for the 2024 Award for Creativity in Molecular Design & Synthesis. The award recognizes initiative, creativity, leadership, and perseverance in pure and/or applied chemistry. Nominees must have had broad impact in the areas of chemical synthesis, method development, bioorganic/medicinal chemistry, pharmaceutical sciences, and/or molecular recognition. Nominations should include a letter describing the nominee’s achievements, a brief biography and curriculum vitae, and a list of the nominee’s important published works. Supporting letters are strongly encouraged. Please submit materials by February 29 to Professor Joseph Badillo: firstname.lastname@example.org. The prize consists of a crystal plaque and a $5,000 honorarium.
Abstract The misfolded proteins associated with neurodegenerative disease can adopt a variety of different conformations, some of which are toxic. Because these proteins have identical amino acid sequences, the cellular environment clearly influences the final state, yet most structural studies do not include the cellular context and, perhaps because we are not studying the correct conformation, not a single therapeutic strategy for these diseases addresses the underlying protein misfolding pathology. Using new sensitivity-enhancement technology for solid state NMR spectroscopy, Dynamic Nuclear Polarization, we study protein structure in native environments -inside living cells -to reveal how both healthy and disease-relevant cellular environments influence protein structure. Because NMR reports quantitatively, with atomic level precision, on all sampled conformation, it can not only report on structural polymorphs but also provide experimental restraints on regions of intrinsic disorder, complementing insights from cryo-electron microscopy and tomography.Using this approach, we recently demonstrated that an amyloid fibril with a solved cryo-EM structure was polymorphic and found that when those fibrils were used to seed amyloid propagation in mammalian cells, the minority polymorph in the purified setting became the majority polymorph inside cells. With this approach we can understand the mechanism of protein-based inheritance of amyloid aggregates and