Targeted theranostic nanovehicles are capable of targeting cerebrovascular amyloid associated with Alzheimer’s Disease and serving as early diagnostic and therapeutic agents across multiple imaging modalities. Assessed in animal models at 21.1 T, these nanovehicles were loaded with gadolinium-based magnetic resonance imaging (MRI), iodine-based single photon emission computerized tomography (SPECT) or fluorescent contrast agents as well as anti-inflammatory and anti-amyloidogenic pharmaceuticals to demonstrate targeted enhancement and treatment in cerebral amyloid angiopathy.
Structures of antimicrobial peptides piscidins 1 and 3 were solved in two bacterial cell mimics by oriented sample solid-state NMR. A significant finding of this work is that in contrast to the ideal structures shown in mechanistic studies of AMPs, the structures of both peptides are disrupted and kinked at a conserved central glycine, which results in stronger interactions with the lipid bilayers. The more pronounced imperfect amphipathicity of piscidin 1 over piscidin 3 that is revealed helps better understand why the former more effectively mixes the lipids as needed to induce the greatest damage to bacterial cells.
GroEL is a large (molecular weight ≈ 800,000) protein complex composed of two heptamers arranged like stacked doughnuts. By “spray-painting” the complex with heavy water, and then cutting into pieces with an enzyme and weighing the pieces, we are able to map the solvent accessibility throughout the complex, and observe conformational changes induced by binding of an analog of adenosine triphosphate (ATP), thereby illuminating the mechanism by which ATP activates the complex for its biological function.
The MagLab’s AMRIS facility has recently implemented dissolution DNP technology. The system utilizes a 5 T magnet in which samples are cooled to 14,000 gain in SNR on dissolution and injection into our 4.7T MRI/S scanner.
Solid state NMR measurements reveal an important structural distinction between different disease-relevant aggregates: oligomers and fibrils. While molecular confirmations are similar within both structures, oligomers differ from fibrils in terms of intermolecular organization of beta-strands.
Using the lab’s 21 tesla magnet to image chlorine in the brain, researchers explore new ways to track tumor growth.
Using a novel combination of techniques, scientists researching the COPII protein created a pseudo-atomic model of the COPII cage, gaining a better understanding of how its 96 subunits fit together.
Using a novel NMR approach, scientists characterize the metabolome of E. coli cells, determining 112 topologies of unique metabolites from a single sample.
This work defines a new mechanism for radical-mediated catalysis of a protein substrate, and has broad implications for applied biocatalysis and for understanding oxidative protein modification during oxidative stress.