Philipp Holliger
Synthetic biology of nucleic acid replication
A critical event in the origin of life is thought to be the emergence of a molecule capable of self-replication as well as mutation, and hence evolution towards more efficient replication. We have built a powerful in vitro system for directed evolution, called compartmentalized self-replication (CSR), which mimics this process in the laboratory.
Our current focus is the application of the CSR technology to the evolution of novel polymerases with an expanded substrate spectrum. Polymerases capable of replicating non-canonical nucleic acid substrates have applications ranging from the recovery of ancient DNA sequences from archaeological and palaeontological specimens to ultra-bright DNA probes for molecular genetics.
Our aims are the generation of artificial genetic systems and the synthesis and evolution of novel, DNA-like polymers for applications in nanotechnology and material science.
We are also aiming to exploit compartmentalization for the evolution of ribozymes capable of replicating their own encoding sequence, with a view to recreate a modern equivalent of the primordial RNA replicase.
Selected Papers
- Taylor, A.I., Pinheiro, V.B., Smola, M.J., Morgunov, A.S., Peak-Chew, S.Y., Cozens, C., Weeks, K.M., Herdewijn, P. and Holliger, P. (2014)
Catalysts from synthetic genetic polymers.
Nature 518: 427-30. - Pinheiro, V.B., Taylor, A.I., Cozens, C., Abramov, M., Renders, M., Zhang, S., Chaput, J.C., Wengel, J., Peak-Chew, S-Y., McLaughlin, S.H., Herdewijn, P. and Holliger, P. (2012)
Synthetic genetic polymers capable of heredity and evolution
Science 336: 341-344. - Wochner, A., Attwater, J., Coulson, A. and Holliger, P. (2011)
Ribozyme-catalyzed transcription of an active ribozyme.
Science 332: 209-211.
Group Members
- Sebastian Arangundy-Franklin
- James Attwater
- Karen Duffy
- Isaac Gallego
- Edoardo Gianni
- Gillian Houlihan
- Wei Liu
- Ben Porebski
- Nithya Subramanian
- Alex Taylor
- Chris Wan