Entry for:The Peer Prize for Women in Science 2017
1. Please give a brief summary of your work.
Crop plants, like us, have pathogens that cause disease. These pathogens have a single goal; consume plant biomass to grow and reproduce, reducing yields. Yield losses in staple crops have far reaching consequences, whereby shortages lead to economic loss, increased food prices and hunger.
A live plant has ways to protect itself from being eaten, which pathogens must work around. How do they do this? Some produce toxins that kill the plant and allow it to feed off the dead tissue. My work focuses on one these toxins, called ToxA. ToxA is unique because it specialises in damaging wheat leaves. Prior to our paper, ToxA was thought to be produced by only two pathogenic fungal species, both of which cause globally important diseases of wheat. Surprisingly, we discovered ToxA in a third fungal species. This new species is a severe pathogen of wheat in food insecure regions of Central Asia.
2. Describe your approach and broader findings.
The problem with agriculture
A typical wheat field is a monoculture, composed of plants that are clones. These clones all grow at the same rate and set seed at the same time, which makes the decision on when to harvest easy. This convenience comes at a high cost. The uniformity of the plants make the entire field vulnerable and a field epidemic rapidly spreads its disease to neighbouring fields. Pathogens evolve mechanisms to attack plants and acquire nutrients from them. Once established, these mechanisms are easily shared within a pathogen species through sexual recombination. A more interesting form of evolution occurs when pathogens exchange DNA between species; a biological process known as Horizontal Gene Transfer (HGT). We observe HGT events by detecting genes or sequences of DNA that are near identical between distantly related species. To an untrained eye, it may appear that these DNA fragments are “copy-and-pasting” themselves between organisms. My work investigates one of these cases, where a single horizontally transferred gene that confers extreme virulence towards wheat, is shared between three fungal species.
ToxA, a selfish gene that kills wheat
I utilise whole genome sequencing to understand how fungal pathogens interact with plants. We have known for some time that the wheat toxin ToxA is produced by two fungal wheat pathogens, Parastagonospora nodorum and Pyrenophora tritici-repentis. These pathogens are hypothesized to have shared ToxA and some surrounding DNA with each other via HGT, resulting in an 11 thousand base sequence that is near identical between the two species. In our study, genome sequencing unexpectedly revealed the presence of ToxA in the genome of the fungal wheat and barley pathogen Bipolaris sorokiniana. Remarkably, ToxA found in our genome assembly has the exact same 11 thousand base fragment that is found in the other two species, with near identical DNA sequence. The high identity shared between these three species indicates that this HGT event must be extremely recent, perhaps occurring within this century. It also demonstrates the value of ToxA itself, which is important enough to be shared between three separate wheat diseases.
We know that ToxA is responsible for necrosis (cell death) on the wheat leaf during infection. It does this in a very specific way by acting in a ‘gene-for-gene’ relationship with a wheat susceptibility gene, Tsn1. If both genes are present, ToxA in the fungus and Tsn1 in wheat, the infected leaf dies. If either gene is absent, then there are no ToxA related symptoms. We tested whether our B. sorokiniana isolates carrying ToxA had higher disease symptoms on wheat varieties that contain Tsn1. Our results unequivocally showed that a B. sorokiniana isolate carrying ToxA has increased leaf necrosis on Tsn1 wheat in comparison to a non-Tsn1 wheat variety. This is important for two reasons: (1) It shows that ToxA plays a critical role in the disease caused by B. sorokiniana (2) There are other unknown virulence factors in B. sorokiniana that damage wheat in the absence of ToxA.
3. What is the wider contribution, or impact, to your scientific field(s)?
ToxA is a threat to global wheat yields
This work further cements Horizontal Gene Transfer (HGT) as a tool through which fungal pathogens can share strategies to exploit host vulnerabilities. HGT is of course not limited to plant pathogens; we know that it plays a central role in the evolution of multi-drug resistant bacteria in hospitals, where we now face bacteria that are resistant to all known antibiotics. In the case of ToxA, we have shown that an identical protein facilitates disease on wheat for three separate fungal diseases. These three diseases are all prominent throughout the wheat-growing world, meaning that ToxA is a global threat to wheat yield. Our work highlights the wide-reaching impact that HGT can have in plant pathogen interactions and the threat it poses to food security.
Field based application of our work
Our work is also immediately applicable to field based control of pathogens carrying ToxA. This is because ToxA has an Achilles heel: it requires the non-essential wheat gene, Tsn1, to induce leaf necrosis. This gene can be selectively bred out of commercial wheat cultivars with no known harm to the plant. Wheat cultivars that do not carry Tsn1 are totally resistant to ToxA and its effects. This strategy was used successfully in Australia to limit the effects of ToxA and increase wheat yields. This knowledge could be critical for farmers and breeders in India and other regions of Central Asia, where B. sorokiniana is a major disease. Removal of Tsn1 from these cultivars could immediately improve yields in regions with poor food security.
4. Are there any potential ideas you would like to explore to take this research further?
Now that we have found ToxA in three different fungal species, there are several remaining questions.
1) Where did ToxA come from?
2) Why is it exceptionally mobile?
3) What is the vehicle for DNA movement between these fungi?
4) Can we prevent ToxA from moving further?
Future work will use whole genome resequencing with cutting-edge long-read technology to answer these questions.
We know from our short-read data that the genomic region surrounding ToxA contains repetitive DNA. This makes it difficult to analyse historical movement of ToxA. Using the Oxford Nanopore MinIon, we will be able to sequence through these repetitive regions and identify the chromosomes that contain ToxA in each species. In doing so we will, for the first time, be able to describe the DNA elements that make ToxA mobile. Once we understand this, we can address the problem of how to limit future movement into other plant pathogens.
Further, it is likely that there are more copies of ToxA in other organisms that we have yet to sequence. The obvious place to start looking is where the gene has its strongest effect; the genomes of other pathogens associated with wheat. We will seek to identify other organisms carrying ToxA by generating new long-read de novo assemblies of un-sequenced wheat pathogens. While this is a risky search, ToxA has proved itself resilient and valuable to these pathogens. Finding its origin is important to understanding how and why wheat became its target.
5. Please share a link for researchers to access a relevant publication, data-set, or thesis.
The discovery of the virulence gene ToxA in the wheat and barley pathogen Bipolaris sorokiniana
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I completed my PhD in population genetics at the prestigious ETH Zurich in 2012, a top 10 world University. My work during my Phd led to a successful fellowship application, which brought me to the...