Differential expression and processing of CABS1 across tissues and fluids and its location-specific functions.

CABS1 在组织和体液中的差异表达和处理及其位置特异性功能。

• 批准号: RGPIN-2020-04553
• 负责人: MarcetPalacios, Marcelo
• 金额: $ 2.19万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=740034
• 关键词: Differential; expression; processing; CABS1; across

In 2015, our research group at the University of Alberta discovered that calcium binding protein, spermatid-associated 1 (CABS1) is detected in human saliva. Previously, CABS1 protein had been found in other species and almost exclusively in the testes. Thus, little was known about CABS1 and its biology. Two years later, a subsequent study by our group showed that CABS1 was involved in control of inflammation and is under neurogenic regulation, with one form of CABS1 in human saliva up-regulated by psychological stress, while smaller sized forms were associated with resilience to stress. This duality of CABS1 ignites many intriguing questions regarding its relevance. My long-term objectives are basic science driven, stemming from a desire to unravel how CABS1 is regulated at the cellular level and determine its functions. In the short term, my objectives are to define epithelial sources of CABS1 production and its processing into multiple forms, as well as the effect of CABS1 on neutrophil biology. Aim 1 of this program will identify CABS1 expression in different tissues and body fluids of rat and human origin, Aim 2 will elucidate the signaling pathways that regulate CABS1 production and release, and Aim 3 will characterize the anti-inflammatory roles of CABS1 on the biology of human neutrophils. I am highly qualified to conduct this research on CABS1 based on my extensive research experience on inflammatory pathways of epithelial and immune cells. My current MSc student and I have already made significant contributions in validating our polyclonal antibodies to CABS1 and we are currently establishing best methodologies for this work, including 2-dimensional electrophoresis coupled with mass spectrometry analysis that will help us carry out components of Aims 1 and 2. I have established strong collaborations with professors with expertise in proteomics and neutrophil biology, who can provide support and advice on our experiments. The foundation of this basic research on CABS1 regulation and function will garner insight on how CABS1 contributes to anti-inflammatory processes. My research may reveal other unrecognized roles of CABS1. This program on CABS1 aligns well with the role of NSERC in helping researchers "produce world-firsts in knowledge". Being the first to elucidate the regulation of CABS1, a curious yet emerging protein with promising results, is an exciting prospect. Establishing a Canadian program for CABS1 research is a step towards global excellence in the field of neuro-endocrine pathways that regulate salivary and other epithelial physiology.

2015年，我们在阿尔伯塔大学的研究小组发现，在人类唾液中检测到钙结合蛋白，精子相关蛋白1（CABS 1）。此前，CABS 1蛋白已在其他物种中发现，并且几乎仅在睾丸中发现。因此，对CABS1及其生物学知之甚少。两年后，我们小组的一项后续研究表明，CABS 1参与控制炎症，并受到神经源性调节，人类唾液中的一种形式的CABS 1受到心理压力的上调，而较小的形式与压力的恢复力有关。CABS 1的这种二元性引发了许多关于其相关性的有趣问题。我的长期目标是基础科学驱动的，源于解开CABS 1如何在细胞水平上调节并确定其功能的愿望。在短期内，我的目标是确定上皮来源的CABS 1生产和其加工成多种形式，以及CABS 1对中性粒细胞生物学的影响。该计划的目标1将鉴定大鼠和人类来源的不同组织和体液中的CAB 1表达，目标2将阐明调节CAB 1产生和释放的信号通路，目标3将表征CAB 1对生物学的抗炎作用人类中性粒细胞。基于我在上皮细胞和免疫细胞炎症通路方面的丰富研究经验，我非常有资格进行这项关于CABS 1的研究。我现在的硕士学生和我已经在验证我们的CABS 1多克隆抗体方面做出了重大贡献，我们目前正在建立这项工作的最佳方法，包括二维电泳结合质谱分析，这将有助于我们实现目标1和2的组成部分。我已经与蛋白质组学和中性粒细胞生物学方面的专业教授建立了强有力的合作关系，他们可以为我们的实验提供支持和建议。这项关于CABS 1调节和功能的基础研究将深入了解CABS 1如何有助于抗炎过程。我的研究可能会揭示CABS1的其他未被认识的作用。CABS1的这一计划与NSERC在帮助研究人员“创造世界第一的知识”方面的作用非常一致。作为第一个阐明CABS 1调控的人，CABS 1是一个有趣但新兴的蛋白质，具有令人兴奋的前景。建立一个加拿大的CABS1研究项目是在调节唾液和其他上皮生理学的神经内分泌途径领域走向全球卓越的一步。