The regulation of plant-nematode parasitism

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Summary: The regulation of plant-nematode parasitism.Plant-parasitic nematodes are a persistent threat to global food security. The most economically important species have the ability to transform plant cells into permanent and dedicated feeding sites. Plants and parasitic nematodes are locked in an "evolutionary arms race". At the front-line, are the parasite "effectors": molecules secreted into the host plant during infection. Plant-parasitic nematodes use hundreds of effectors to manipulate their host. Often individual effectors target a specific function in the host. The scientific community has focused on trying to understand and block these effector functions.A vulnerability of this approach is that for thousands of years plants have been deploying resistance genes to recognise effectors, and mount an immune response. This means that the parasites are under a strong evolutionary selection pressure to counteract this, developing a number of mechanisms to evade or negate effector recognition (sequence diversity, partitioning effectors in regions of the genome that mutate rapidly, functional redundancy, etc.). Practically, this means that targeting individual effectors to control the parasite is rarely highly successful, and unlikely to be robust. What we need is a series of new targets that have not been the focus of this kind of evolutionary selection pressure.This proposal is designed to deliver new targets by shifting the focus away from individual effectors to "high-level" functions: how is parasitism regulated? The idea is that if we can disrupt the process of parasitism regulation we can disrupt the functions of many effectors at the same time. Two recent breakthroughs in our understanding of parasitism regulation suggest that now is the right time to initiate this shift in focus.In 2016 I identified a regulatory genetic signature of nematode effectors. This signature unifies hundreds of otherwise unrelated effectors. This implies there is some nematode regulatory machinery that recognises this signature, and in so doing orchestrates this aspect of parasitism. I predict that if we could disrupt this "master-regulator", it would in turn disrupt hundreds of associated effectors. In a recent effort I have identified a candidate for such a regulator.The second breakthrough is the discovery that nematodes do not synthesise all effectors at the same time, suggesting that they may be delivered in waves that indicate a complex "parasitism programme" during infection. This sequential programme of effector production suggests that there will be a series of additional regulators that are activated at specific time-points. Disrupting any of these is likely to be severely detrimental to the parasite. Importantly, the plant immune system is "blind" to these master regulators. This means that they are unlikely to be protected by the same mechanisms that make targeting effectors so difficult. Together, this suggests that parasitism master regulators will be an attractive set of targets for control. In this proposal I will identify, validate, and disrupt these master-regulators.The fact that parasitic nematodes predictably execute a "parasitism programme" also gives us some insights into how they transform plant tissues. It suggests that the regulation of feeding site formation in the host is probably a multi stage process, and has the same or a very similar number of stages. This is a new insight into how this tissue is formed and presents an opportunity to understand the fundamental biology that underpins this process. In this proposal I will develop a system to measure changes in the host gene regulation and link these changes to progression through the nematode parasitism programme, ultimately building the foundation to understand this phenomenon.