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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=684810
• 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性物质的能力，广泛的分布以及生态和经济重要性，蓝贻贝长期以来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示剂。因此，已经开发了相对大量的生物标志物来确定蓝贻贝的健康状况。这些生物标志物允许早期检测由于暴露于压力源而导致的生物变化，这可能导致长期的生理紊乱。在最常见的生物标志物中，有反映形态学改变的组织学生物标志物和反映基本细胞机制改变的功能性生物标志物。然而，在大多数情况下，这些方法需要现场经过培训的组织解剖和/或不间断的冷链取样，以保持样品的质量。对于在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有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。支撑组学技术的高通量过程的出现为克服这些障碍和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了癌症和其他疾病临床管理的重大转变。在这里，我们建议利用在这一领域取得的巨大进展，特别注意液体活检的概念。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，用于评估正在进行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）卡的开发新的组学为基础的生物标志物联合收割机。我们将使用这种方法来研究不同栖息地类型的贻贝在时间和空间变化条件下的细菌微生物组。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，研究胁迫因素对贻贝ccfDNA和细菌微生物组的影响。在短期内，这些研究将有助于更好地了解贻贝与其环境之间的关系。它也将允许推进我们的知识的病理生理机制牵连的发展压力相关的反应贻贝暴露于人类活动。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，用于海洋生态系统健康的纵向监测。