Investigations of kinase-mediated cell signaling pathway modulation at the vector-pathogen-livestock interface in vector-borne livestock diseases.

在媒介传播的牲畜疾病中媒介-病原体-牲畜界面激酶介导的细胞信号通路调节的研究。

• 批准号: RGPIN-2018-06036
• 负责人: Kindrachuk, Kenneth
• 金额: $ 2.7万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=760775
• 关键词: Investigations; kinase; mediated; cell; signaling

Vector-borne pathogens, including bacteria and viruses, are an increasing threat to livestock health. Vector-borne diseases that impact livestock species have the potential to disrupt agronomic health and food security with the greatest impacts in developing nations. In addition, climate change has expanded the global distribution of many vector species (e.g. ticks, mosquitoes) resulting in increased likelihood of pathogen introductions to new geographic regions thus increasing the potential impact on other countries that rely heavily on agricultural exports such as Canada. Management of these vectors and vector-borne diseases in livestock species remain a major challenge. Unfortunately, there is a lack of knowledge regarding the molecular events underlying the vector-pathogen-host transmission cycle. My proposed NSERC research program will focus on characterizing vector-pathogen-host transmission cycles in livestock species with a focus on tick-borne (Coxiella burnetti) and mosquito-borne (Rift Valley fever virus; RVFV) diseases. Over the next 5 years, I will investigate the kinase mediated signaling events involved in the transmission cycle. Together with my HQP, I will apply species-specific kinome analysis with kinome peptide arrays to characterize the global activation states of kinases in both vector- and livestock-species. Specifically, we will: i) create vector- and livestock-specific kinome arrays using bioinformatics approaches; ii) characterize both vector-specific and livestock-specific kinome responses following pathogen insult (C. burnetti and RVFV); and iii) determine the functional role of cell signaling pathways and individual kinases identified from our kinome analyses on pathogen persistence and innate immune response dysregulation. By using a complex data approach to investigating the fundamental processes underlying transmission of vector borne diseases, the proposed research will build a wealth of knowledge laying the foundation for future expansion of detailed molecular studies. My program will train HQP with a broad skillset including use of bioinformatics tools, molecular biology, and biochemistry. They will develop expertise in areas of virology, bacteriology, entomology and livestock diseases, thus preparing them for a wide range of careers in the life sciences ranging from microbiology to veterinary medicine.

包括细菌和病毒在内的病媒病原体对牲畜健康的威胁越来越大。影响牲畜物种的病媒传播疾病有可能破坏农业健康和粮食安全，对发展中国家的影响最大。此外，气候变化扩大了许多病媒物种（如蜱、蚊子）的全球分布，导致病原体传入新地理区域的可能性增加，从而增加了对加拿大等严重依赖农产品出口的其他国家的潜在影响。在牲畜物种中管理这些病媒和病媒传播疾病仍然是一项重大挑战。不幸的是，有一个缺乏知识的分子事件的基础上的媒介-病原体-宿主的传播周期。 我提议的NSERC研究计划将侧重于表征牲畜物种中的媒介-病原体-宿主传播周期，重点是蜱传（Coxiella burnetti）和蚊传（裂谷热病毒; RVFV）疾病。在接下来的5年里，我将研究参与传递周期的激酶介导的信号事件。与我的HQP一起，我将应用特定物种的激酶组分析与激酶组肽阵列来表征载体和牲畜物种中激酶的全局激活状态。具体而言，我们将：i）使用生物信息学方法创建载体特异性和牲畜特异性激酶组阵列; ii）表征病原体损伤后载体特异性和牲畜特异性激酶组应答（C. burnetti和RVFV）;和iii）确定从我们的激酶组分析中鉴定的细胞信号传导途径和单个激酶对病原体持久性和先天免疫应答失调的功能作用。通过使用复杂的数据方法来调查媒介传播疾病传播的基本过程，拟议的研究将积累丰富的知识，为未来扩展详细的分子研究奠定基础。我的项目将培训HQP广泛的技能，包括使用生物信息学工具，分子生物学和生物化学。他们将发展病毒学，细菌学，昆虫学和牲畜疾病领域的专业知识，从而为从微生物学到兽医学的生命科学领域的广泛职业做好准备。