A continuous wave and pulsed electron paramagnetic resonance (EPR) spectrometer is requested by investigators at MIT, Harvard Medical School and its affiliated institutions, and other institutions in the Boston metropolitan area. The instrument's capabilities include pulse electron nuclear double resonance and pulse electron (electron) double resonance. The instrument will complement high-end X-ray crystallography, nuclear magnetic resonance (NMR), and electron microscope (EM) capabilities in the Boston area to enable multidisciplinary structural biology investigations of questions that are of great biological and medical importance. Research projects from seven groups (Griffin, Springer, Reinherz, Wagner, Lippard, Stubbe, and Nocera) are outlined, and those from another seven groups are briefly summarized.
The instrument will advance the following health-related research: 1) methods development for solid-state NMR; 2) the structure of amyloid fibrils which is of importance to the etiology and treatment of amyloid diseases, especially Alzheimer's disease; 3) signal transmission through the plasma membrane by integrins and epidermal growth factor receptor (EGFR), to advance understanding and therapy of thrombosis, rheumatoid arthritis, asthma, and psoriasis (integrins) and lung, breast, and head and neck cancer (EGFR); 4) the structure of human immunodeficiency virus (HIV) membrane proximal ectodomain regions, with or without bound broadly neutralizing antibodies, to design better immunogens for HIV vaccines; 5) the mechanism of radical formation and long-distance proton-coupled electron transfer in ribonucleotide reductases, to improve chemotherapy in hematological cancers; 6) the structure of a complex between a voltage-dependent anion channel and pro-apoptotic proteins, to improve cancer therapies; and 7) the mechanism of difficult metabolic transformations using polymetallic centers in enzymes, of relevance to the greenhouse gas methane and development of anticancer and antiviral drugs. Further projects target membrane proteins important in neurological disease and anesthesia; and viral and bacterial proteins important in infectious disease and defense against biological warfare agents. ? ? ?
