UPDATE: This project is filled.
At the Center for Computational and Applied Transcriptomics (COAT), experimental and computational methods are being used to investigate RNA structure and RNA-protein interactions on a transcriptome wide scale to enable the design of effective and safe RNA drugs (more information at rna.dk). As part of COAT, Santaris Pharma is looking for a bioinformatics masters student to work on a project as described below.
Outline of project
RNA molecules are single-stranded molecules with a strong tendency to fold back on themselves and form Watson-Crick pairs, leading to secondary structural motifs of various lengths and complexities. These motifs can further assemble into intricate three-dimensional architectures. RNA structure is a key element in many regulatory processes (Westhof and Romby, Nat Methods, 2010), and, more pragmatically, may limit the accessibility of RNA drugs (modified oligonucleotides designed to be reverse complementary to their target RNAs).
Experimentally, high-throughput sequencing technology have recently been used to determine RNA secondary structure in full transcriptomes of yeast (Kertesz et al., Nature, 2010) and mouse (Underwood et al., Nat Methods, 2010) cells.
Computationally, RNA structure prediction can be based on deriving minimal free energy structures that maximizes the number of base pairs and uses empirical estimates of thermodynamic parameters for neighbouring interactions and loop entropies (Zuker and Stiegler, NAR, 1981, and Hofacker et al., 1994). Alternatively, comparative genomics methods that assume different evolutionary pressures on single-stranded and double-stranded parts of a folded RNA molecule can be used (Pedersen et al., PLoS Comput Biol, 2006). The thesis project will compare the experimentally observed structures derived from the sequencing data with the predictions made from these methods.
Based on this work, possible accessibility limitations due to secondary structure will be evaluated for a number of RNA molecules and compared with Santaris Pharma’s experimentally observed performances of sets of LNA-modified oligonucleotides designed against each of them.
- Fluency in R and perhaps also in Python or similar.
- Solid understanding of RNA biology.
- Experience with analysing sequencing data is a plus
For information about how to apply, please see this post.