CrgA, a key Mycobacterium tuberculosis cell division protein that recruits five other proteins to the cell division apparatus has been structurally characterized using oriented sample and magic angle spinning solid state NMR. The protein has two transmembrane helices and an intrinsically disordered N-terminus. Binding sites have been identified for it's binding partners. Evaluating these binding sites may lead to effective drugs for either promoting and inhibiting cell division, both of which are of prime interest for the treatment of tuberculosis.
13C NMR when used in metabolomics 1. Provides better peak list for database matching and spectral annotation, 2. Provides better group separation and loadings annotation when using multivariate statistical analysis, and 3. Prevents possible misidentification of metabolites.
By coupling selective band excitation of metabolites with high magnetic fields, relaxation-enhanced 1H MR spectroscopy can be performed in living specimen and patients to achieve high sensitivity over very short acquisition times for the examination of cellular dysfunction. This sensitivity can be used to evaluate otherwise inaccessible metabolites or regions of the proton spectral regime and can be used to probe cell-specific environments, such as neurons versus astrocytes, that may undergo differential changes during dysregulation.
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.