How does PcNMRAL1 orchestrate infection-associated gene expression changes during host colonisation?

辣椒疫霉等真核生物病原体在多种植物上引起严重的病害。如果我们渴望防止真核生物病原体造成的损失，我们必须阐明导致疾病的机制。我们发现了令人信服的新证据，表明辣椒疫霉中一种保守的转录调控因子PcNMRAL1有助于以阶段特异的方式调节病原体编码的基因补体的表达。我们假设PcNMRAL1是一个调节因子，有助于协调基因表达的变化，从而导致从生物营养性感染阶段向坏死性感染阶段的转变。为了验证这一假设，我们将干扰PcNmraL1，并评估其对病原体毒力、疾病周期和PcNMRAL1反应基因表达的影响。然后，我们将确定与PcNMRAL1相互作用的细胞信号蛋白和转录调节因子，并帮助调节基因表达。最后，我们将使用现有的基因表达数据来确定PcNMRAL1响应元件，然后将其部署在CasID实验中，以精确定位导致基因调控的分子事件。通过回答有关半营养生物的基因调控及其对毒力的影响的基本问题，我们将开辟新的途径，通过新的化学控制策略来识别和利用特定阶段的代谢线索。学生将有机会在项目框架内发展和应用他们自己的想法，并为他们的研究提供指导。我们将允许在研究方向方面有高度的灵活性，因为可以调整方法，一旦产生初始数据，后续实验就可以专注于非常具体的方向。

Eukaryote pathogens such as Phytophthora capsici cause significant disease on a wide range of plants. If we aspire to prevent losses incited by Eukaryote pathogens, we must elucidate the mechanisms that enable disease. We have uncovered compelling new evidence demonstrating that a conserved transcriptional regulator in P. capsici, PcNMRAL1, helps regulate the expression of pathogen-encoded gene complements in a stage-specific manner. We hypothesise that PcNMRAL1 is a regulator that helps orchestrate changes in gene expression that lead to the transition from the biotrophic to the necrotrophic infection stage. To test this hypothesis, we will disrupt PcNmraL1 and assess the impact on pathogen virulence, the disease cycle and the expression of PcNMRAL1 responsive genes. We will then identify cellular signalling proteins and the transcriptional regulators that interact with PcNMRAL1 and help regulate gene expression. Finally, we will use existing gene expression data to identify PcNMRAL1 responsive elements and that will then be deployed in CasID experiments to pinpoint the molecular events that lead to gene regulation. By answering fundamental questions pertaining gene regulation in hemi-biotrophs and its impact upon virulence, we will open up new avenues by which stage-specific metabolic cues can be identified and exploited through novel chemical control strategies. The student will be giving the opportunity to, within the framework of the project, develop and apply their own ideas and give direction to their research. We will allow a high degree of flexibility with regards the direction of the research in that approaches can be adapted, and follow-up experiments can be focused into very specific directions once initial data is generated.