The processes of RNA synthesis and DNA repair are fundamental for life. RNA synthesis and DNA repair reactions are carried out by specialized nanomachines, which recognize DNA sequences and structures, catalyze formation and cleavage of chemical bonds, generate mechanical forces, and initiate and respond to biological signals. The principles by which these processes occur are not understood, and coupling of biology and engineering is required to provide quantitative descriptions and models that enable reliable prediction of process outcomes as well as design of interventions and biocompatible nanodevices. One objective of the Georgia Nanomedicine Center (GNC) is to elucidate the engineering principles involved in these nanomachines. Significant technological challenges exist in achieving this goal. Current technologies are unable to measure the behavior of single molecules in living cells. Such measurements are clearly essential, however, to obtain a full description of biological processes in engineering terms. Thus, another part of the GNC mission is to develop technologies capable of providing information about molecular processes at the single-cell and single-molecule levels. Examples of biological problems to be addressed include: maintenance of the unineme chromosome; correction of DNA replication errors; beta-globin transcription factories; and distribution of mRNA during asymmetric cell division. Examples of new nanotechnology tools to be developed include: bioconjugated quantum dots; dual-FRET and peptide-linked molecular beacons; magnetic nanoparticle probes for deep tissue imaging; and STED-4pi light microscope for optical imaging with a spatial resolution of 30 to 50 nm. This planning grant will help the project team to: (a) identify additional problems relevant to RNA synthesis and DNA repair that would benefit from the availability of nanotechnology tools, (b) identify additional tools (including computational/modeling tools), beyond those discussed in this memorandum, that will be needed to mount a comprehensive approach to solving these biological problems, and (c) develop the collaborative structure and mechanisms through which the GNC will function, including interactions with other Nanomedicine Centers. The planning process will include a workshop to be held in Atlanta, which will provide a forum for discussions with potential collaborators in the Southeast and nationwide. Approximately 20 investigators, distributed among the Emory/Georgia Tech/MCG consortium and also outside research centers, will be invited. Some investigators will be experts in biological problems, others in relevant areas of technology and modeling. The detailed plan for the GNC will be developed from results of this workshop and also through further preliminary studies that couple nanotechnology tools and models with the selected biological phenomena.
