Research Overview


In brief, the objectives of CMR are: to develop sophisticated technologies for magnetic resonance in the areas of solution-state NMR, solid-state NMR, electron paramagnetic resonance (EPR), and dynamic nuclear polarization (DNP); to apply those technologies to biologically and medically significant research, both in-house and collaboratively; to operate a state-of-the-art instrument facility to serve needs of researchers in chemistry, biology, and medicine; and to openly disseminate and provide training in technological developments at the Center.

In solution-state NMR, the focus is on the study of protein interactions, such as the intermolecular effects on structure and function of human translation initiation factors such as eIF4E, eIF4A, eIF4G, eIF1, eIF1A, eIF5 and their interaction with each other, with regulatory proteins or the small ribosomal particle. Similar studies are focused on proteins regulating transcriptional activation in human and in pathogenic yeast strains. Other efforts involve complexes regulating immune cell biology. Another example is the voltage-dependent anion channel VDAC-1 of the outer mitochondrial membrane and it’s interaction with the ADP/ATP transporter that is located in the inner mitochondrial membrane. Some of the structural information is used for the design of anti-tumor or immune-suppressive agents. Many of these studies have required the development of advanced pulse sequences and non-uniform sampling protocols with suitable data reconstruction techniques. These which are being extended to the study of integral membrane proteins by the use of new labeling schemes and NMR technologies such as the use of phospholipid nanodiscs, bilayers and amphipoles, as well as novel methods of sample orientation in order to obtain structural restraints from reduced dipolar couplings. The NUS approach is also successfully extended to solid-state NMR spectroscopy.

In solid-state NMR, the focus is on MAS and DNP studies of proteins, such as those related to energy transduction in the ion-motive photocycle of bacteriophodopsin, and amyloid fibrils, such as beta-2-microglobulin, a protein involved in a medical disorder known as dialysis-related amyloidosis. Other examples include the study of amyloid fibrils of human transthyretin, and the study of apo- and drug-bound structures of the M2 protein from influenza A virus. The examples mentioned so far have been concerned with dipolar nuclei such as 1H, 13C, 15N, and 31P but more than half of the periodic table is composed of quadrupolar nuclei, therefore methodology is being investigated to study nuclei such as 2D, and 17O, particularly at high field and high spinning frequencies. All these various studies have required the development of probes for low temperature MAS and DNP, in parallel with the development of high frequency microwave sources for magnetic resonance.

   

Francis Bitter Magnet Laboratory
NW14, 150 Albany Street
Cambridge, MA 02139
Phone: (617) 253-5478
Email: jhaggert@mit.edu