PROJECT
Tracking evolution and biosynthesis of cyclic peptide natural products
Search for circular proteins and their origins throughout the plant kingdom
Cyclic peptides are ultra-stable with many activities claimed for them. In plants they get cut from within precursor proteins and some have taken an evolutionary shortcut by appearing from within what then becomes a host protein.
The genetic events that created them are diverse ranging from millions to tens of millions of years old. The huge and diverse families have activities like blocking enzymes while others have drug potential.
The ability to find these peptides is now accelerated by a tailored algorithm, which coupled to RNA-seq will reveal a huge variety of natural products with potential benefits to biomedicine, plant biology and biotechnology.
As part of this project the successful PhD applicant will:
- Extract RNA from plants known or suspected of having cyclic peptides for which no gene sequence information is known. The RNA-seq data will be used to assemble transcriptomes which will reveal the gene encoding the peptides. Mass spectrometry will be used to confirm the predictions and accelerate discovery of related peptides. Candidates will be made and tested in bioactivity assays.
For more background information see the suggested readings below.
- Suggested readings
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- Mark F. Fisher, Jingjing Zhang, Oliver Berkowitz, James Whelan, and Joshua S. Mylne (2020). Cyclic Peptides in Seed of Annona muricata Are Ribosomally Synthesized. Journal of Natural Products Article ASAP
- Bahar Behsaz, Hosein Mohimani, Alexey Gurevich, Andrey Prjibelski, Mark Fisher, Fernando Vargas, Larry Smarr, Pieter C. Dorrestein, Joshua S. Mylne, Pavel A. Pevzner (2020). De Novo Peptide Sequencing Reveals Many Cyclopeptides in the Human Gut and Other Environments. Cell Systems, 10 (1), 99-108.e5
- Jingjing Zhang, Colton D. Payne, Benjamin Pouvreau, Hanno Schaefer, Mark F. Fisher, Nicolas L. Taylor, Oliver Berkowitz, James Whelan, K. Johan Rosengren, and Joshua S. Mylne (2019). An Ancient Peptide Family Buried within Vicilin Precursors. ACS Chemical Biology, 14 (5), 979-993
- Mark F. Fisher Jingjing Zhang Nicolas L. Taylor Mark J. Howard Oliver Berkowitz Aleksandra W. Debowski Bahar Behsaz James Whelan Pavel A. Pevzner Joshua S. Mylne (2018). A family of small, cyclic peptides buried in preproalbumin since the Eocene epoch. Plant Direct, 2 (2).
- Achala S. Jayasena, Mark F. Fisher, Jose L. Panero, David Secco, Kalia Bernath-Levin, Oliver Berkowitz, Nicolas L. Taylor, Edward E. Schilling, James Whelan, Joshua S. Mylne (2017). Stepwise Evolution of a Buried Inhibitor Peptide over 45 My. Molecular Biology and Evolution, 34 (6), 1505–1516
Research team leader: Associate Professor Joshua Mylne
I'm a geneticist and biochemist who has worked broadly in plant genetic engineering, developmental genetics, epigenetics and peptide biochemistry; I am in the School of Molecular Sciences at UWA where I founded my lab in 2013. My research has included studies in protein evolution, biosynthesis and (in close collaboration with synthetic organic chemist Keith Stubbs) increasingly been on herbicide development and target discovery.
Collaborations and Funding
- Professor Jim Whelan, La Trobe
- Associate Professor Johan Rosengren, The University of Queensland
- Professor Pavel Pevzner, UCSD, USA
- Associate Professor Mikael Elias, University of Minnesota
- If this sounds interesting to you, get in touch!
Funding:
- ARC Discovery Project DP190102058 “Buried treasure: bioactive plant seed proteins evolving inside hosts” Mylne, Rosengren, van der Hoorn, Hara-Nishimura; $422,000; 2019-2021
How to apply
Interested in becoming part of this project? Complete the following steps to submit your expression of interest:
Step 1 - Check criteria
General UWA PhD entrance requirements can be found on the Future Students website.
Requirements specific to this project:
- Molecular biology or biochemistry experience is desirable, but a project could also be tailored to someone with a more bioinformatics-heavy background.
Step 2 - Submit enquiry to research team leader
Step 3 - Lodge application
After you have discussed your project with the research team leader, you should be in a position to proceed to the next step of the UWA application process: Lodge an application. Different application procedures apply to domestic and international students.
Scholarships
- Domestic students
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All domestic students may apply for Research Training Program and University Postgraduate Awards (UPA) scholarships.
The Australian Government's Endeavour Awards and Scholarships are available to Australian applicants for study in participating countries and regions.
- International students
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A range of scholarships are available from international organisations and governments. The full list, organised by country, is available on the Future Students website.
In addition, all international students may apply for International Research Training Program scholarships.
The Australian Government's Endeavour Awards and Scholarships are available to international applicants from participating countries and regions.
- Indigenous students
- Indigenous students are encouraged to apply for Indigenous Postgraduate Research Supplementary Scholarships.
- Forrest Foundation scholarships
- All international and Australian students who wish to study towards the degree of Doctor of Philosophy (PhD) at The University of Western Australia may apply for Forrest Scholarships.
Proteins date back to the time of sabre toothed cats
Plant scientists at The University of Western Australia have discovered a completely new family of small proteins called PLPs (PawL Peptides) that form by piggybacking on other proteins. The scientists found ‘protein-piggybacking’ of PLPs began in seeds of a daisy ancestor that existed 45 million years ago during the Eocene Epoch period - around the time sabre toothed cats walked the earth.
Read moreProteins hiding in proteins take an evolutionary shortcut
How a drug-like protein ring evolved in sunflowers has been pieced together by Australian and US scientists in a study published in Molecular Biology and Evolution. Although the evolutionary process took some 45 million years, the researchers are still calling it a shortcut. The study team included researchers from The University of Western Australia; La Trobe University in Melbourne, the University of Tennessee and the University of Texas.
Read moreMylne Lab Research - Plant Biological Chemistry
In close collaboration with the Stubbs lab and guidance from AHRI, our lab is discovering chemically new herbicides and exploring new possible modes of action.
Read more
