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: 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=760823
• 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，精子细胞相关1(CABS1)。此前，在其他物种中也发现了CABS1蛋白，而且几乎只在睾丸中发现。因此，人们对CABS1及其生物学知之甚少。两年后，我们团队的一项后续研究表明，CABS1参与了炎症的控制，并处于神经性调节之下，人类唾液中的一种形式的CABS1受到心理压力的上调，而较小的形式与对压力的弹性有关。CABS1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，源于一种愿望，即解开CABS1是如何在细胞水平上调节并确定其功能的。在短期内，我的目标是确定CABS1产生的上皮来源及其加工成多种形式，以及CABS1对中性粒细胞生物学的影响。本项目的目标1将鉴定CABS1在大鼠和人类来源的不同组织和体液中的表达，目标2将阐明调节CABS1产生和释放的信号通路，目标3将表征CABS1在人中性粒细胞生物学中的抗炎作用。基于我在上皮细胞和免疫细胞炎症途径方面的丰富研究经验，我完全有资格对CABS1进行这项研究。我和我目前的硕士学生已经在验证我们的CABS1多克隆抗体方面做出了重大贡献，我们目前正在为这项工作建立最佳方法，包括二维电泳和质谱分析，这将帮助我们实现AIMS 1和2的组件。我已经与具有蛋白质组学和中性粒细胞生物学专业知识的教授建立了密切的合作关系，他们可以为我们的实验提供支持和建议。这项关于CABS1调控和功能的基础研究将有助于深入了解CABS1如何参与抗炎过程。我的研究可能会揭示CABS1的其他未被认识的角色。CABS1上的这个项目与NSERC在帮助研究人员“创造知识的世界第一”方面的作用非常一致。第一个阐明CABS1的调控是一个令人兴奋的前景。CABS1是一种奇怪的新兴蛋白质，结果很有希望。建立加拿大CABS1研究计划是在调节唾液和其他上皮生理学的神经内分泌通路领域朝着全球卓越迈出的一步。