We propose to expand the NMR resources at the University of Washington (UW) by acquiring a 800 MHz NMR spectrometer capable of performing both solution and solid state NMR experiments. The number of research groups in the Seattle area involved in performing biological solid state and/or biological solution NMR independently or collaboratively has increased dramatically in recent years. The need for access to ultra-high field NMR equipment (i.e. >600 MHz) has increased at least proportionally. Only a few years ago biological solid state NMR (ssNMR) was performed by a single major user (Drobny) and collaboratively by one or two minor users (Stayton and later Castner). Now all three major users on this proposal (Drobny, Klevit, Varani) have ongoing projects in solid state NMR. The single DMX-750 at UW is poorly equipped to do solid state NMR and in any case not enough ssNMR time is available on the DMX-750 at UW to accommodate the projects of three major users and several minor users. Likewise the number of research groups at UW and at the Fred Hutchinson Cancer Research Center with on-going solution NMR studies of biological macromolecules has also increased to the point that there is simply not enough NMR capacity at any field in the Seattle area to meet this demand, a situation especially serious because of the technical limitations of the DMX-750 magnet, which prevent it from performing long-run high resolution NMR experiments. Therefore, even major users Klevit and Varani must apply for large slots of spectrometer time at PNNL and elsewhere. That so many groups in the Seattle area have to travel to remote locations to access ultra-high field NMR equipment or have to be content to await access locally to lower field NMR instruments as the opportunity arises, demonstrates that we need to expand the capacity to do ultra-high field NMR in the Seattle area. We respectfully request that NIH provide the funding to us so we can acquire a solid state/solution 800 MHz spectrometer that will serve the current needs of our major and minor users.
Knowledge of the structure and dynamics of biomolecules is fundamental to understanding their function and is therefore a vital component of our ability to understand and treat human disease. Solid state and solution NMR spectroscopies are able to elucidate structure and dynamics of biological macromolecules in solution, in microcrystalline and amorphous solid form, adsorbed onto biomaterial surfaces or oriented in lipid bilayers. Members of our user group are funded predominantly by NIH and to some extent also by NSF to use NMR and other methods to study a wide variety of proteins and nucleic acids, with relevance to developing treatments for a variety of cancers, heart disease, HIV, and optimizing the performance and design of biomedical implants, biosensors, and engineered tissues.
| Byrne, Aimee; Kier, Brandon L; Williams, D V et al. (2013) Circular Permutation of the Trp-cage: Fold Rescue upon Addition of a Hydrophobic Staple. RSC Adv 2013: |
