862 LGRT B
The Martin Lab is interested in understanding specific chemical interactions which underlie complex enzyme systems. A major focus of the lab has been to understand structure and function in enzyme-nucleic acid interactions. In transcription, the enzyme RNA polymerase must not only bind specifically to its promoter DNA sequence but must then initiate the processive catalysis of template-dependent RNA synthesis, leave the initial recognition site (promoter), and continue on to a stable, sequence-independent complex, adding thousands of monomers precisely to the growing RNA.
The T7 family of RNA polymerases present an ideal model system for the study of transcription. This single subunit polymerase is relatively simple and there are now a wealth of structures to generate testable mechanistic models for function. Towards these ends, we have exploited the chemical synthesis of DNA oligonucleotides containing specifically modified base substituents, including fluorescent base analogs.
While chemical synthesis of relatively short DNA fragments has provided us very powerful tools, research in RNA biochemistry has exploded, in part enabled by T7 RNA polymerase, which can readily synthesize RNAs thousands of bases in length. Our attention is now turning towards making RNA polymerase a better tool for synthesis of RNA in the lab. Combining our decades of experience with new tools and approaches, we are taking a mechanistic approach to enhancing practical applications. We are very excited about the prospects for new discoveries in the world of RNA, the central molecule in life’s Central Dogma.