News

Thursday, 16 August 2018
The structural co-ordinates for the macrocyclizing protease butelase 1 were released by the Protein Data Bank today with accession number 6DHI.
Friday, 10 August 2018
Check out this interview by Josh with the Laymans Podcast; two young guys interested in science and communication, operating from their parents' back garden shed.
Tuesday, 31 July 2018
We have nervously entered the preprint world with our manuscript "The macrocyclizing protease butelase 1 remains auto-catalytic and reveals the structural basis for ligase activity" published today on bioRxiv.
Archived Lab News

Plants, proteins and their evolution
Our research has two separate foci; applied work on herbicides and fundamental research on biosynthesis and the genetic events that evolve new plant proteins, especially ones with pharmaceutical applications. Our herbicide research aims to find as many new modes of action possible, whereas our more fundamental work on protein evolution provides opportunities to engineer these valuable molecules as well as insights in enzymology.

Our applied herbicide work is based largely on our finding that, thanks to the established close evolutionary relationship between plants and the malarial parasites, many antimalarial drugs are also herbicidal. We are trawling malarial drug libraries for novel herbicide chemistries, but also thinking more broadly about the plant-malaria connection and seeking to exploit that link. We also hope that using plants we might reveal the mode-of-action for these novel herbicides, but also potentially under-studied antimalarial drugs. Our fundamental protein evolution work is based on precursor proteins and the biosynthetic routes we discovered 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 structural biology and next-generation sequencing which suits our current location, we are asking; 1) what genetic events have evolved drug-like peptides in plants; 2) what are the enzymatic mechanisms plants use to make these cyclic peptides; and 3) with some drug-like peptides evolving in a buried fashion in 'host' proteins, is this a more universal mechanism for creating new proteins while bypassing the need for a completely new gene?.

Plant Biology

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.

Herbicides

New modes of action from the plant-malaria connection

Plants and the malarial parasite are more closely related than many people would think. We showed that many antimalarial drugs are herbicidal and this has spurred new ways of thinking about what new herbicides could be developed, but also offers an opportunity to use plants to study antimalarial drugs. The looming threat of resistance is driving a need to discover truly new herbicides.

Biochemistry

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 host. It is offering an opportunity to study the co-option of proteases to perform ligation reactions as well as determine whether hijack is a universal mechanism for evolving new proteins within existing genes.