- Friday, 24 March 2017
- Over 110 new transcriptomes were used to the birth and evolution of SFTI-1 in our new Mol. Biol. Evol. paper that was indexed today in PubMed and the article "Stepwise evolution of a buried inhibitor peptide over 45 million years" by Achala Jayasena et al. can be viewed using its DOI. A press release also just came out.
- Wednesday, 22 March 2017
- A short review on AEPs authored with PhD student Amy James and Dr Joel Haywood just went live in the Wiley Online Library, click DOI to access it at New Phytologist or go via PubMed.
- Wednesday, 15 March 2017
- Our paper by Amy James and colleagues just came online at The Plant Cell: "Evidence for Ancient Origins of Bowman-Birk Inhibitors from Selaginella moellendorffii". Click for Press Release or go straight to the paper by DOI. Archived Lab News
Our research examines the genetic events that evolve new plant proteins, especially ones with pharmaceutical applications. This not only provides fundamental new knowledge about protein evolution, but also provides opportunities to engineer plants to produce these valuable molecules.
We have discovered precursor proteins and the biosynthetic routes for three very different classes of cyclic peptides, all of interest to drug designers. Combining a background in classical genetics and developmental biology with the biomedical atmosphere of our current location, we find our interests falling into three related areas of research that ask; 1) what are the genetic events that evolved drug-like peptides in plants; 2) how do plants make the peptides created by these genetic events plus how malleable are plants as a drug production system; and 3) can plants reveal the mode-of-action for drugs and enable the design of new drugs? Our goal is to convince the scientific community that plants are not just a source of drugs, but also a viable platform to produce and study them.
Plant 'genetic backflips' make bioactive peptides
We have characterised the genetic origin for several different peptides of great interest to drug designers and each time we find a precursor, it seems each plant has undergone a genetic rearrangement event to make the peptides. We seek to understand why plants are going out of their way to make such bioactive peptides as well as understand how some of the genetic events came about.
Plants to make new drugs and understand existing drugs
Understanding the biosynthetic route for gene-encoded, bioactive peptides allows one to move these genes into other species and use them as production systems. We are currently working on two seed production systems, one via a sunflower protein and another from a gourd (pumpkin family) family of proteins. We have also started using the model plant Arabidopsis to study in-use human drugs.
How plants bend, fold, cut and glue proteins into rings
We have stumbled upon an extraordinary case of protein hijack in sunflower where a protease inhibiting peptide ring is processed out of a much larger and completely unrelated protein. It is offering an opportunity to study the co-option of proteases to perform ligation reactions as well as begin to appreciate the role that chaperones play in this process both in vitro and in vivo.