Specifically, we ask how the capacity to store and propagate information, how life’s first genetic system arose and why information storage and propagation in biological systems is based on just two types of nucleic acids, DNA and RNA. Is the chemistry of life’s genetic system based on chance or necessity? Does it reflect a "frozen accident", imposed at the origin of life, or are DNA and RNA functionally superior to simple alternatives.
We are working on 1) the synthesis, replication and evolution of entirely synthetic genetic polymers (XNAs) capable of information storage, propagation and evolution and 2) the reconstruction of a key component of the RNA world, an RNA molecule capable of self-replication and mutation and hence, evolution towards ever more efficient self-replication and the potential role of water ice in that process.
A synthetic genetic polymer with an uncharged backbone chemistry based on alkyl phosphonate nucleic acids.
Arangundy-Franklin S, Taylor AI, Porebski BT, Genna V, Peak-Chew S, Vaisman A, Woodgate R, Orozco M, Holliger P.
Nature Chemistry 2019 Apr 22. doi: 10.1038/s41557-019-0255-4
Random-sequence genetic oligomer pools display an innate potential for ligation and recombination.
Mutschler H, Taylor AI, Porebski BT, Lightowlers A, Houlihan G, Abramov M, Herdewijn P, Holliger P.
eLife 2018 7: e43022. doi: 10.7554/eLife.43022.
Ribozyme-catalysed RNA synthesis using triplet building blocks.
Attwater J, Raguram A, Morgunov AS, Gianni E, Holliger P.
eLife 2018 7: e35255. doi: 10.7554/eLife.35255.
Simple peptides derived from the ribosomal core potentiate RNA polymerase ribozyme function.
Tagami S, Attwater J, Holliger P.
Nature Chemistry 2017 9: 325-332. doi: 10.1038/nchem.2739.