This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The major goals of our lab are to understand mechanisms that govern gene regulatory networks and to create synthetic molecules such as artificial transcription factors (ATFs) that can be engineered to control these networks in a predetermined manner. ATFs, due to their ability to stimulate transcription, will complement the siRNA approach and serve as powerful, functional, genomics tools that identify and control the gene networks which govern cell fate. They will also contribute to the nascent field of synthetic biology and metabolic network engineering by proving to be a versatile tool in the regulatation of submodules of gene networks. As the ultimate value of ATFs lies in their potential application as precision-tailored therapeutic agents, we aim to regulate transcriptional circuitry by creating synthetic molecules that mimic the properties of natural transcription factors or counteract the activity of malfunctioning genetic machinery. It is therefore of the utmost importance that the identities of the molecules (i.e., synthetic mimics) we synthesize are confirmed via thorough structural analyses before proceeding further. We wish to incorporate NMR data as the primary method of structural validation, corroborated by mass spec and HPLC data. Although this particular project probably requires only low field NMR analysis (400 MHz), we are currently planning other projects which would require resolution of more complicated proteins therefore necessitating the use of much higher magnetic fields.
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