My current research focuses on RNA, the much less publicized nucleic acid compared to DNA. DNA carries genetic information, and proteins carry out gene regulatory roles, while RNA has typically been thought of as the "in-between" molecule with much less biological significance. However, there has been a recent influx of evidence that RNA plays many more different roles biologically, beyond the textbook examples of messenger RNA and transfer RNA.
Like proteins, the function of RNA depends on its environment, which in turn affects its structure. Hence it is imperative to understand how RNA behaves, folds and adopts intricate three dimensional structures. I've been studying RNA structure, and DNA behavior both in vitro and in silico in the hope of gathering more insight to the physical principles driving nucleic acid structure.
I am currently taking the computational approach towards answering these questions, but my previous experimental background has also helped shape my research direction, and establish valuable connections and collaborations with experimentalists.
- RNA Knowledge Based Potential
The number of RNA high resolution crystal structures solved has grown significantly and this provides us with an invaluable database for RNA motifs and structures. We are currently studying how well knowledge based potentials developed from this database can help in structure prediction and refinement, in particular in combination with efficient sampling tools (see below). This work in done together with Julie Bernauer who is currently in INRIA, France.
- Sampling RNA Structures
In collaboration with Peter Minary in the Levitt Lab, we have been studying sampling methods for RNA and DNA structures using a series of naturalized moves that reduce the sampling degrees of freedom. This will make computational sampling more tractable, in order to more effectively study nucleic acid structures in silico.
- Small Angle X-ray Scattering Structural Filters
As a natural follow-up from my experimental SAXS days, I'm also looking at combining SAXS data with structural models generated from RNA structure prediction tools to guide the selection of RNA models that fit experimental data well.
- Scaling Behavior of Single-stranded DNA
Single stranded nucleic acids are prevalent in biology, and studying how they behave in solution can guide models for predicting loop formation and shed some light on how unfolded RNA behaves. We study the sequence dependence of polymer properties of single stranded DNA under a variety of salt conditions. The simplicity of the system makes this experimental study a useful model for testing nucleic acid force-fields used computationally.
- Understanding the Glycine Riboswitch
Using small angle x-ray scattering experiments while in the Doniach Lab, we studied the global structure of the glycine riboswitch, which has two aptamer domains that bind to glycine cooperatively.