The objective of this workshop is to establish a coalition of scientists interested in identifying and pursuing priority research directions aiming at resolving plasticity of the biological functional physical structure of the living state around the cellular level in space and time, starting with tissue and down to the level of molecular constituents, bridging the gap between structural biology and genomics technologies in a spatio-temporal systems biology approach, with a focus on spatially resolved solid state nuclear magnetic resonance imaging and spectroscopy techniques with sensitivity enhancement, at the highest possible magnetic field.
Motivation of the workshop
Magnetic resonance imaging and localized spectroscopy are well-known tools in medicine and molecular biology. Forging the tools for NMR imaging at the level of the cell and down to the level of molecules, including spectroscopic investigations of cellular constituents, requires a merger between MRI methods and AFM methods and can be the next step in NMR imaging research: Magnetic Resonance Force Microscopy (MRFM). Successful implementation of this technology will represent a fundamental breakthrough in instrumentation in life science (systems biology) and nanoscience investigations. In the workshop we will bring the experts together to draft a road map, identifying the hurdles and knowledge gaps that need to be resolved, plus possible solutions.
There are two major application areas that make this workshop timely. First, genomics is producing a comprehensive image of the “information space” in the living cell. The number of targets for medical intervention is presently exploding, and this raises the question why a certain pathway or target is important, and why others are less important. The answer is in the structural plasticity, small variations of the functional physical structure of sub-cellular entities down to the level of the molecule. However, these will be different for different cells and will also be different between individuals, since biology is a matter of extremes, rather than averages. To go from high throughput to high content, broadly applicable magnetic resonance techniques at the (near) molecular level will be very useful. In 10-15 years these techniques will provide new avenues to personalized medicine and will make it possible to follow personalized health indicators such as misfolded proteins by nuclear magnetic resonance assays. These developments also have a large potential to improve our understanding of biological processes that form the living state. Second, the integration of functional components in nanotechnology will result in a multitude of nanoscale devices of great variety and displaying a plethora of very different properties. Hence, a detailed characterization of the features of such integrated systems at the fundamental physical level is crucial. In particular we must be able to probe and understand sequences of molecular events. Next to conventional high-resolution microscopies such as AFM and electron microscopy the development of high-resolution (spatial, temporal) spectroscopies is essential to reveal information about functional nano-architectures and to facilitate their construction. Nanomaterials will be available in small amounts, and highly sensitive detection schemes need to be applied that do not yet exist. MRFM is such a detection scheme with the potential of resolving the signals down to the level of single nuclear spins.
As all nuclear magnet resonance methods, MRFM has intrinsically low selectivity and sensitivity. In principle single-spin sensitivity is possible, however, by optimizing gradient and cantilever designs. For (selective) imaging of small ensembles of spins at ambient temperatures, RF induced, microwave induced and light-induced dynamic nuclear polarization methods, based on polarization transfer from electrons to nuclei, will be necessary to overcome these limits. In the workshop these issues will be addressed and possible solutions will be identified.