Grant: Research Tools and Instruments

This grant will be used to provide a research-grade circular dichroism (CD) spectrophotometer allowing new avenues of protein science and engineering research at Dalhousie University. Proteins may either be in a spaghetti-like (unfolded) chain or they may have a defined, ""folded"" structure. CD spectroscopy allows a relatively fast and robust characterization of the amount of unfolded vs. folded protein present under a given set of conditions. Furthermore, the actual nature of the folded state is directly reflected in the CD spectrum. All four of the co-applicants and their current roster of 16 trainees, ranging from undergraduate students developing research expertise to senior postdoctoral fellows, will be able to immediately take advantage of this instrument for fundamental studies of proteins critical for life in diverse organisms including humans, fungi, and spiders. The requested CD spectrophotometer will be used to study proteins, such as spider silks, surface active fungal hydrophobins, and enzymes that have potential for new biomedical applications. Researchers will gain the ability to track changes in the folded state of these proteins. This may happen when proteins bind to each other, possibly forming biologically-active fibres, gels, droplets, nanoparticles, or films. Of critical importance, this binding process may change the protein fold, in turn changing its functional state. CD spectroscopy provides the capability to both monitor these changes and to probe the underlying folded state. These types of study are being employed by the applicants to engineer and develop new biodegradable materials and proteins that make critical chemical processes more efficient. All of the applicants rely extensively on CD spectroscopy, with current instrumentation being both heavily subscribed and having significant maintenance concerns after ~19 years of heavy use. Unlike the existing legacy instrument, a wide variety of sample types ranging from liquids to protein films to magnetically-oriented samples will be amenable to study with this new instrument, greatly expanding the applicants' capabilities to characterize proteins in their truly functional state. The requested instrument also, importantly, has outstanding temperature control capabilities, meaning that temperature-dependent phenomena such as protein folding/unfolding or self-assembly into larger structures can be far more accurately and reproducibly studied.The new instrument will be installed in the Biophysical Analysis Facility housed in Dalhousie's Department of Biochemistry Molecular Biology, providing ready access to the co-applicants and to many other researchers at Dalhousie and the Maritimes. Rather than providing access to the instrument in a service-type manner, trainees will be directly supported in developing expertise in hands-on use of the instrument and in analyzing the resulting data.