Dried Blood Spot Biomarker Development for Addressing Evolutionary and Biocultural Questions

生物标志物是生物过程的客观测量，有助于描述个体的生理状况。在这个项目中，研究人员将开发和验证六种微创干血斑生物标志物，与现代人群，适应和生活史的研究相关。尽管用于社会和行为科学的生物标志物的开发和应用取得了重大进展，但仍需要解决关键问题和局限性，并系统地开发和优化生物标志物。该项目开发的生物标志物将支持生物人类学和人类生物学中有关压力，衰老和免疫功能的重要理论问题的调查，并将为未来的干血斑检测开发制定标准。将建立一个质量控制样本的生物库，并与希望开发自己的生物标志物的其他实验室共享，以便在研究和实验室之间进行比较。该项目还将为本科生和研究生提供教育培训机会。这项研究将开发和验证六种干血斑免疫测定生物标志物，以扩大生物人类学的方法工具包，应用于该领域的四个主要主题：1）自身免疫性疾病（髓过氧化物酶[pANCA]，炎症性肠病的指标，和抗甲状腺过氧化物酶抗体[TPOAb]，自身免疫性甲状腺疾病的标志物）; 2）调节全身炎症（抗炎细胞因子白细胞介素-10 [IL-10]）; 3）骨转换（羧化骨钙素[cOC]，骨形成的标志物，和抗酒石酸酸性磷酸酶5 b [TRACP 5 b]，骨吸收的标志物）;和，4）应激相关的老化（蛋白质标志物Klotho）。项目团队将使用来自俄勒冈州尤金地区的200名成年人的匹配干血斑和静脉穿刺获得的全血样本开发这些检测。本研究中使用的评价、修改和验证的系统过程是开发DBS生物标志物的最严格策略，所得出版物将作为进一步生物标志物验证工作的基准。该研究将导致：1）6篇技术出版物，含试验验证和方案; 2）详细的书面试验方案（多种语言）和视频说明，可在一个公开的储存库; 3）生物库材料，跨实验室协调可根据要求提供给其他实验室; 4）研究生的技术培训; 5）为12名本科生提供本科研究机会，包括来自代表性不足人口的本科生;以及6）在关于干血斑的科学状态的全国会议上的一次会议。

Biomarkers are objective measures of biological processes that help to describe an individual's physiological condition. In this project, the investigators will develop and validate six minimally-invasive dried blood spot biomarkers with relevance to studies of modern human populations, adaptation, and life history. Despite significant progress on the development and application of biomarkers for use in the social and behavioral sciences, there is a need to address critical issues and limitations, and to systematically develop and optimize biomarkers. The biomarkers developed in this project will support the investigation of important theoretical questions in biological anthropology and human biology about stress, aging, and immune function, and will set the standard for future dried blood spot assay development. A biobank of quality control samples will be created and shared with other laboratories that wish to develop their own biomarkers, so that results will be comparable across studies and laboratories. The project will also provide educational training opportunities for undergraduate and graduate students. This research will develop and validate six dried blood spot immunoassay biomarkers in order to expand the methodological toolkit in biological anthropology for application to four topics of major interest to the field: 1) autoimmune disease (myeloperoxidase [pANCA], an indicator of inflammatory bowel disease, and anti-thyroid peroxidase antibody [TPOAb], a marker of autoimmune thyroid disorders); 2) regulation of systemic inflammation (the anti-inflammatory cytokine interleukin-10 [IL-10]); 3) bone turnover (carboxylated osteocalcin [cOC], a marker of bone formation, and tartrate-resistant acid phosphatase 5b [TRACP5b], a marker of bone resorption); and, 4) stress-related aging (the protein marker Klotho). The project team will develop these assays using matched dried blood spot and venipuncture-obtained whole blood samples from 200 adults from the Eugene, Oregon area. The systematic process of evaluation, modification, and validation to be used in this study is the most rigorous strategy to develop DBS biomarkers and the resulting publications will serve as benchmarks for further biomarker validation efforts. The research will result in: 1) six technical publications with assay validations and protocols; 2) detailed written assay protocols (in multiple languages) and video instructions available in a publicly available repository; 3) biobank materials for cross-laboratory harmonization available upon request to other labs; 4) technical training of a graduate student; 5) undergraduate research opportunities for 12 undergraduates, including those from underrepresented populations; and 6) a session at a national conference on the state of the science with respect to dried blood spots.