Anderson - Plant innate immunity proteins
Our group works on protection of humans and crops from pathogens. We do this by studying natural defences of plants, and the biology of the pathogens themselves.
Plants lack an adaptive immunity system. Instead, they have evolved complex innate immune mechanisms to defend against microbial infection and insect damage. We study several classes of small, disulphide-rich innate immunity proteins, focusing on fungicidal and insecticidal activities. Additionally, by understanding how pathogenic fungi build their cell walls and adapt to treatment with fungicides, we are identifying new strategies and targets for controlling them.
Our work spans from initial discovery to final application of these molecules. We use high-throughput screening of Australian native plants to find insecticidal and antifungal molecules. Detailed bioinformatic, biochemical and genetic methods are used to understand their evolution, biosynthesis, and mechanisms of action. Finally, we develop these proteins for commercial applications in crop protection and human antifungal therapeutics, in collaboration with the biotechnology company Hexima.
Fungi are an ever increasing threat to human health and agricultural crops. Combatting fungal infection is difficult because there are few exploitable differences between host and pathogen. Our antifungal research aims to identify novel antifungal molecules and targets.
Harnessing plant innate immunity peptides: Plants lack the adaptive immune system found in mammals and are fully dependent on innate immune systems composed of a variety of small molecules and proteins to protect against infection. Our main focus has been on a family of plant innate immunity peptides called defensins, a diverse family of small proteins which share a compact structure of 3 beta strands and an alpha helix stabilized by 4 disulphide bonds. Current research in the Anderson lab is centred on understanding the links between sequence diversity and mechanisms of action. These defensins are being developed for use in both disease-resistant transgenic crops and for the treatment of superficial fungal infections in humans.
Identifying new targets for antifungal molecules: Current antifungal target either the unique fungal cell wall or a fungi-specific cell membrane component (ergosterol). These drugs typically have problems with off-target toxicity and developing fungal resistance. We are investigating patterns of gene and protein expression in fungi under biotic and abiotic conditions to better understand the infection process and identify new targets for the development of antifungal molecules. We are also characterising the cell wall biosynthetic machinery using genomics, transcriptomics and proteomics to identify targets to inhibit.
Naturally occurring circular proteins (in which the N- and C-termini are linked by a peptide bond) offer enhanced stability over their linear counterparts. Of particular interest is a plant-derived group of cyclic peptides called cyclotides, which are further stabilised by three disulphide bonds that form a conserved cysteine knot motif. Cyclotides exhibit a range of intrinsic bioactivities, such as insecticidal, anti-HIV and neurotensin binding, and their exceptional stability marks them as promising scaffolds for the grafting of other bioactive sequences for pharmaceutical applications. Achieving efficient backbone-cyclisation in vitro has hindered the realisation of this potential.
Native cyclotides are produced as precursors that are enzymatically processed to their mature, cyclic form. Our lab has identified a vacuolar processing enzyme (VPE) from a cyclotide producing plant that is capable of performing the final processing step: removal of the C-terminal prodomain and circularisation of the peptide backbone. We are now focussing on harnessing the potential of this enzyme for large scale production of both naturally and non-naturally occurring cyclic peptides using in vitro and in vivo systems.
Natural product screening
Finding new ways to protect crop plants from insect damage is vital for the world's food production by optimising the productivity of the world's limited arable land. Current anti-insect technologies have been in the market for more than 10 years and resistance to these traits is beginning to develop, creating a need for new technologies.
Our lab uses high-throughput robot-assisted screening for insecticidal activity to hunt for new insecticidal proteins in plant extracts. By expressing these proteins in transgenic plants, we aim to commercialise their use for crop protection in collaboration with DuPont Pioneer. This research program combines the experience of Pioneer researchers in characterizing novel insect actives and trait development with our lab's expertise in biochemistry and insect biology. In parallel with this, we are also generating an extensive library of Australian native plant extracts which can be screened for other novel molecules including molecules with antifungal activities.
Meet the team
Dr Susanna Herd
Donovan Garcia Ceron
A Method: WO 2017/054044 A1
Generation of Peptides: WO 2017/049362 A1
A Method of in vivo Treatment: WO 2016/191790 A1
A Method of Treatment: WO 2016/061619 A1
Agents and methods for treatment of pathogens: WO 2015/161346 A1
Agents and methods of treatment: WO 2015/161348 A1
Anti-pathogenic methods: WO 2014/078900 A1
Novel plant defensins and use in the treatment of proliferative diseases: WO 2013/056309 A1
Use of antifungal defensins: AU 2013/260696 A1
Defensin variants and methods of use: US 2012/0054911 A1
Novel antifungal proteins and methods of use: US 2012/0102595 A1
Modified plant defensins useful as anti-pathogenic agents: WO 2012/106759 A1
Treatment of proliferative diseases: WO 2011/160174 A1
Plant anti-pathogen systems: WO 2010/015024 A1
Anti fungal methods: WO 2009/094719 A1
Multi-gene expression vehicle: WO 2007/137329 A9
Nucleic acids encoding plant defensins and methods of use thereof: WO 2004/001012 A2
Insect chymotrypsin and inhibitors thereof: WO 2004/094630 A1
Defensin polynucleotides and methods of use: US 2003/0041438 A1
Plant-derived molecules and genetic sequences encoding same and uses therefor: WO 2002/063011 A1
Novel nucleic acid molecules: WO 2001/034829 A2