From decoding RNA-peptide interactions to building an RNA ecosystem
Long non-coding RNA is thought to play a major role as a structural and organisational element in cell biology and development. The dynamic interactions between non-coding RNA and various intrinsically disordered proteins (IDP – effectively very long unfolded peptide chains) leads to the formation of condensates that are often referred to as liquid-liquid phase separated (LLPS) droplets. As a chemistry-research group, we entered this field, noting the similarities between these RNA-protein droplets/LLPS and peptide-gels – materials that we have been studying for a considerable time.[1-2]
Building on our peptide work, we therefore hypothesised that even very short RNA and peptide could under the right conditions form gel-like aggregates. More importantly, these studies should give us a detailed molecular level understanding of how RNA and peptides/proteins interact to form liquid-liquid phase separated structures and other condensates. This includes investigating: condensates formed between short peptide such as triglycine-X-triglycines and pentanucleotide RNA oligo’s. e.g., AAXAA (X = variable amino acid or nucleotide). These initial studies are already providing valuable new insight into the factors that at the (sub)-molecular level control RNA-peptide interactions, and in doing so take us a step closer to decoding the language that controls RNA-peptide/protein interactions.
Having also worked for a decade within the field of nanomedicine and targeted delivery with nanoparticles, the potential important of understanding better how peptides could also aid in the delivery of RNA therapeutics was not lost on us. After first approached our state government in 2019, the recent pandemic and the successful deployment of mRNA vaccines then enabled us to work with other like-minded scientists from Universities and Medical research organisation from across country, including ANU, to advance the vision of making Australia a powerhouse in the emerging RNA ecosystem.
Prof. Pall Thordarson (Palli) obtained his BSc. from the University of Iceland in 1996 and a PhD in Organic Chemistry from The University of Sydney in 2001. Following a Marie Curie Fellowship in the Netherlands he returned to Australia in 2003 and was then appointed at UNSW Sydney in 2007 as a Senior Lecturer where he became a Full Professor in 2017. He is currently the Director of the newly formed UNSW RNA Institute and the President-Elect of the Royal Australian Chemical Institute (RACI). He is also a program leader for the NSW RNA Production and Research Network and leads the NSW RNA Bioscience Alliance on the behalf of the NSW Vice-Chancellor’s Committee.
Palli has published over 130 referred papers, including in prestigious journals such as Nature and Nature Nanotechnology. His research interest ranges from Nanomedicine and Light-harvesting Materials to Supramolecular and Systems Chemistry. He is focused on advancing our understanding of how molecules interact with one other and ‘self-assemble’, and how self-assembly can then be harnessed to create novel functional materials and systems. He has received a number of awards including the 2012 Le Fèvre Memorial Prize from the Australian Academy of Science for outstanding basic research in Chemistry by a Scientist under the age of 40.
- A. D. Martin, A. B. Robinson, A. F. Mason, J. P. Wojciechowski, P. Thordarson, Chem. Commun. 50, 15541-15544 (2014).
- J. P. Wojciechowski, A. D. Martin, P. Thordarson, J. Am. Chem. Soc. 140, 2869-2874 (2018).
- K. C. Tjandra, N. McCarthy, L. Yang, A. J. Laos, G. Sharbeen, P. A. Phillips, H. Forgham, S. M. Sagnella, R. M. Whan, M. Kavallaris, P. Thordarson, J. A. McCarroll, J. Med. Chem. 63, 2181 (2020).