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。在该项目中，研究人员将开发并验证六种与现代人类群体、适应和生活史研究相关的微创干血斑生物标志物。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研究，并将为未来干血斑测定的发展制定标准。将创建质量控制样本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，以便研究和实验室之间的结果具有可比性。该项目还将为本科生和研究生提供教育培训机会。本研究将开发和验证六种干血斑免疫分析生物标志物，以扩展生物人类学的方法工具包，应用于该领域主要感兴趣的四个主题：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（抗炎细胞因子白介素-10 [IL-10]）； 3) 骨转换（骨形成标志物羧化骨钙素[cOC]和骨吸收标志物抗酒石酸酸性磷酸酶5b [TRACP5b]）； 4) 与压力相关的衰老（蛋白质标记 Klotho）。该项目团队将使用来自俄勒冈州尤金地区 200 名成年人的匹配干血斑和静脉穿刺获得的全血样本来开发这些检测方法。本研究中使用的评估、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。该研究将产生：1）六份技术出版物，其中包含测定验证和方案； 2) 公开可用的存储库中提供详细的书面测定方案（多种语言）和视频说明； 3) 可根据其他实验室的要求提供用于跨实验室协调的生物样本库材料； 4）研究生技术培训； 5) 为 12 名本科生（包括来自弱势群体的本科生）提供本科生研究机会； 6) 全国会议上有关干血斑科学状况的会议。

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.