Molecular Determinants of Calcitic Biomineralization.

方解石生物矿化的分子决定因素。

• 批准号: RGPIN-2022-04803
• 负责人: Hincke, Maxwell
• 金额: $ 2.84万
• 依托单位: University of Ottawa
• 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=746582
• 关键词: Molecular; Determinants; Calcitic; Biomineralization.

Flaws in chicken eggshell (ES) fabrication are a human health and food safety issue; the nutritious table egg is an important source of protein, minerals and vitamins for hundreds of millions of individuals living in poverty worldwide. In this sense, the reproducible nature of calcitic biomineralization of the eggshell is of critical concern to human society. In Canada, it is estimated that about 10,000 annual cases of salmonella poisoning are due to contamination of cracked and imperfect eggshells that find their way into the food chain. Worldwide, foodborne salmonella is responsible for 80.3 million illnesses/yr (1.35 million cases/yr in the United States). In the USA, salmonella poisonings result in 26,500 hospitalizations/yr and 420 deaths/yr. Approximately 18% of salmonella outbreaks are due to consumption of food prepared from contaminated eggs.    My NSERC Discovery research program has an overall aim to investigate the integrated defense strategies that function at the eggshell as a biomineralized barrier in order to maintain the pathogen-free status of the egg.  During 2016-2022 [evidenced in 16 publications and 1 book chapter], our detailed proteomic and transcriptomic studies of eggshell biomineralization in chicken, guinea fowl and duck, in addition to analysis from a broad multi-omics evolutionary perspective, have provided insight into nature's toolkit that is responsible for avian eggshell formation. Our recent publication in Nature Communications emphasizes the critical role that eggshell-specific C-type lectin matrix proteins (ovocleidin-17 in chicken) play in eggshell mineralization. We identified a new vesicular pathway for amorphous calcium carbonate (ACC)-mediated eggshell mineralization and assessed the relevance of a new molecular actor (EDIL3). Moreover, the role of osteopontin in modulating eggshell nanostructure and hardness was confirmed.    However, the eggshell possesses dual functions as both a biomineralized barrier and as a component of the innate immune system. Disentangling immune and biomineralization mechanisms represents a significant challenge to understand how organisms integrate biomineral formation and immune plasticity with the maintenance of critical physical protection. The general goals of my NSERC Discovery research during the next grant cycle are to study the innate immune role of the chorioallantoic membrane (CAM) during ES weakening and microbial challenge, and to further investigate the role of ACC in ES resorption (CAM-mediated demineralization).  We will use transcriptomics (RNA-Seq) and proteomics approaches to investigate the hypotheses that the CAM responds to mechanical and microbial insults by up-regulating its protective mechanisms, and that stabilized ACC is a readily mobilized source of calcium precursor during embryonic growth. These studies will lead to solutions to serious food safety issues such as salmonella contamination of the table egg.

鸡蛋壳（ES）制造中的缺陷是一个人类健康和食品安全问题;营养丰富的餐桌鸡蛋是全球数亿生活在贫困中的人的蛋白质，矿物质和维生素的重要来源。从这个意义上说，蛋壳的方解石生物矿化的可再生性对人类社会至关重要。在加拿大，据估计，每年约有10，000例沙门氏菌中毒事件是由于破裂和不完美的蛋壳污染而进入食物链。在全球范围内，食源性沙门氏菌每年造成8030万例疾病（美国每年135万例）。在美国，沙门氏菌中毒每年导致26，500人住院治疗，420人死亡。大约18%的沙门氏菌爆发是由于食用了由受污染的鸡蛋制成的食物。 我的NSERC发现研究计划的总体目标是研究蛋壳作为生物矿化屏障发挥作用的综合防御策略，以保持鸡蛋的无病原状态。在2016 - 2022年期间[16篇出版物和1本书章节]，我们对鸡，珍珠鸡和鸭蛋壳生物矿化的详细蛋白质组学和转录组学研究，除了从广泛的多组学进化的角度进行分析外，还提供了对自然界中负责鸟类蛋壳形成的工具包的深入了解。我们最近在Nature Communications上发表的文章强调了蛋壳特异性C型凝集素基质蛋白（鸡中的ovocleidin-17）在蛋壳矿化中的关键作用。我们确定了一个新的囊泡途径无定形碳酸钙（ACC）介导的蛋壳矿化，并评估了一个新的分子演员（EDIL 3）的相关性。此外，骨桥蛋白在调节蛋壳纳米结构和硬度中的作用得到证实。 然而，蛋壳具有双重功能，既是生物矿化屏障，又是先天免疫系统的组成部分。解开免疫和生物矿化机制是一个重大的挑战，了解生物体如何整合生物矿物形成和免疫可塑性与维持关键的物理保护。在下一个资助周期，我的NSERC发现研究的总体目标是研究绒毛尿囊膜（CAM）在ES弱化和微生物挑战过程中的先天免疫作用，并进一步研究ACC在ES吸收中的作用我们将使用转录组学（RNA-Seq）和蛋白质组学方法来研究CAM通过上调其保护机制来响应机械和微生物损伤的假设，稳定的ACC是胚胎生长过程中钙前体的一个容易动员的来源。这些研究将导致解决严重的食品安全问题，如餐桌鸡蛋的盐污染。