Since the physicist Richard Feynman famously remarked that “[t]here is Plenty of Room at the Bottom” half a century ago, rapid advances in science have shown us that these words do not only apply to the realm of physics, but equally well to all other the disciplines that make up the exciting fields of biophysics and life sciences. However, the chemistry, biology, and physics we find at this “bottom”, at the level of individual molecules and molecular aggregates, are succinctly different from what one encounters on the macroscopic scale: thermal motion becomes important, while inertia plays a very minor role; and the statistics of large numbers encountered in the test tube have to be replaced with analysis of discrete interaction between a few partner molecules. From this follows that all structures build from nanometre sized (molecular) units and all their interactions are highly dynamic and susceptible to disturbances by exceedingly small forces in the low pico-newton (10^-12 N) range.
The aim of this career integration proposal is to expand my previous work on the effects of small mechanical forces in the interaction of DNA with regulatory proteins, and extend it to establish the dynamic mechanical parameters of novel non-standard, self-assembled DNA structures based on the self-recognition of the DNA base guanine, which show potential as building blocks for future molecular-scaled devices and electronics (“G-wires”). Putative poly-guanine structures have been reported to occur ubiquitously in the human genome, where they make up the highly repetitive ends of chromosomes (telomers) and are found throughout regulatory sequences of the genetic code (“G-quadruplexes”); this makes them potential targets for therapeutic drugs in the fight against cancer. Although the chemical environment needed for assembly has been studied, little to nothing is known about their physical properties, especially on the biologically and technologically relevant single molecule level.
Call for proposal
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