Liquid biopsies for monitoring the health status of blue mussels

用于监测蓝贻贝健康状况的液体活检

• 批准号: RGPIN-2019-06607
• 负责人: StPierre, Yves
• 金额: $ 2.4万
• 依托单位: Institut national de la recherche scientifique
• 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=757485
• 关键词: Liquid; biopsies; monitoring; health; status

Because of their ability to accumulate xenobiotics in their tissues, wide distribution, and ecological and economical importance, blue mussels have long been recognized as good biological indicators for monitoring the effects of pollution and climate change in marine ecosystems. A relatively large number of biomarkers have thus been developed to determine the health status of blue mussels. These biomarkers allow early detection of biological changes due to exposure to stressors, which may result in long-term physiological disturbances. Among the most common biomarkers, there are histological biomarkers, which reflect morphological alterations, and functional biomarkers, which reflect alteration in basic cellular mechanisms. In most cases, however, these approaches require on-site trained tissue dissection and/or uninterrupted cold chain sampling to maintain quality of samples. For sampling in remote areas, such as polar regions, this implies complex logistical challenges and considerable risk and cost associated with shipment and storage. These difficulties represent a major obstacle for long-term monitoring of impacts of climate change in marine ecosystems. The advent of high-throughput processes underpinning omics technologies provides a new opportunity to overcome these obstacles and to develop "next-generation biomarkers" that are compatible with modern sampling technologies. In medicine, these biomarkers have led to a significant shift in the clinical management of cancer and other diseases. Here, we propose to take advantage of the tremendous progress that has been achieved in this field with a particular attention to the concept of liquid biopsy. Using a small sample of blood, clinicians can easily and quickly obtain vital information that are used to assess ongoing tissue damage or to measure with high precision the efficacy of a given treatment. We propose to apply this concept and combine it with the Flinders Technology Associates (FTA) cards for the development of novel omics-based biomarkers. We will use this approach to study the bacterial microbiome of mussels in different habitat types across temporally and spatially varying conditions. We will also characterize and study circulating cell-free DNA (ccfDNA) fragments in plasma of mussels, with a particular attention to the circulating virome and methylome. Finally, we will conduct laboratory experiments to study the effects of stress factors on ccfDNA and the bacterial microbiome of mussels. On a short-term basis, these studies will contribute to a better understanding of the relationship between mussels and their environment. It will also allow advance our knowledge on the pathophysiologic mechanisms implicated in the development of stress-related responses of mussels following exposure to anthropogenic activities. On a long-term basis, the program will help to develop next-generation multi-omics-based biomarkers for longitudinal monitoring of marine ecosystem health.

由于其在组织中积累外源物质的能力、分布广泛以及生态和经济重要性，蓝贻贝长期以来一直被认为是监测海洋生态系统污染和气候变化影响的良好生物指标。因此，已经开发出相对大量的生物标志物来确定蓝贻贝的健康状况。这些生物标志物可以及早检测由于暴露于压力源而导致的生物变化，这些变化可能导致长期的生理紊乱。在最常见的生物标志物中，有反映形态变化的组织学生物标志物和反映基本细胞机制变化的功能生物标志物。然而，在大多数情况下，这些方法需要现场训练的组织解剖和/或不间断的冷链采样以保持样品的质量。对于极地等偏远地区的采样，这意味着复杂的后勤挑战以及与运输和储存相关的相当大的风险和成本。这些困难是长期监测气候变化对海洋生态系统影响的主要障碍。支持组学技术的高通量过程的出现为克服这些障碍并开发与现代采样技术兼容的“下一代生物标志物”提供了新的机会。在医学上，这些生物标志物导致癌症和其他疾病的临床管理发生重大转变。在这里，我们建议利用该领域已取得的巨大进展，特别关注液体活检的概念。使用少量血液样本，临床医生可以轻松快速地获得重要信息，用于评估持续的组织损伤或高精度测量给定治疗的疗效。我们建议应用这一概念并将其与弗林德斯技术协会 (FTA) 卡相结合，以开发基于组学的新型生物标志物。我们将使用这种方法来研究不同栖息地类型在时间和空间变化条件下的贻贝细菌微生物组。我们还将表征和研究贻贝血浆中的循环无细胞 DNA (ccfDNA) 片段，特别关注循环病毒组和甲基化组。最后，我们将进行实验室实验来研究应激因素对贻贝ccfDNA和细菌微生物组的影响。从短期来看，这些研究将有助于更好地了解贻贝与其环境之间的关系。它还将增进我们对贻贝暴露于人类活动后应激相关反应的发展所涉及的病理生理机制的了解。从长远来看，该计划将有助于开发下一代基于多组学的生物标志物，用于纵向监测海洋生态系统健康。