Paul Paukstelis

Our laboratory is broadly interested in nucleic acid structure. Using x-ray crystallography and other biophysical techniques we are currently exploring how proteins can influence RNA structure, and how non-canonical DNA base pairing motifs can be used to rationally design three-dimensional nanostructures.

Protein-dependent group I intron splicing
Group I introns splice through a series of RNA-catalyzed reactions. While many group I introns can splice in vitro, most if not all require proteins for efficient splicing in vivo. CYT-18, the mitochondrial tyrosyl-tRNA synthetase from Neurospora, is a bifunctional protein that can promote the splicing of a wide variety group I introns by stabilizing their catalytically active RNA structure. With a crystal structure of a CYT-18/ group I intron complex now in hand, we are currently exploring the mechanistic details of how several small adaptations in the CYT-18 protein can promote essential interactions within the RNA to form a functional 'RNPzyme'.

Structural DNA nanotechnology
Creating 3-D DNA crystals has been recognized as a major step towards the application of DNA nanotechnology. We described the first rationally designed 3-D DNA crystals, based on a predictable non-canonical base pairing motif. Subsequently, we have demonstrated that these crystals contain a network of solvent channels in which macromolecules can be adsorbed or excluded based on size. Building on this work, we are continuing to develop DNA-based technologies at the emerging interface between biology, materials science, and engineering. Future work will probe the diversity of non-canonical base pairing motifs present in short oligonucleotides, and the application of 3-D DNA crystals as molecular scaffolds for crystallizing proteins.