Selective Detection and Quantification of DNA Lesions

DNA氧化损伤是一个重要的生物学和化学复杂的过程。当DNA暴露于氧化条件下时，会产生大量（50种）化学修饰（损伤）。DNA损伤与衰老和疾病的发展有关。因此，它们作为“生物标志物”有助于预测疾病的发作和衰老过程的进展。该项目的目标是开发用于检测细胞DNA损伤的简便、灵敏的化学方法。此外，PI将创建用于病变检测的化学方法，其他科学家将使用其他实验室和/或商业供应商生产的常用仪器和试剂。这种化学反应也将能够确定特定DNA损伤和突变热点之间是否存在相关性。检测端粒中或细胞DNA中确切位置的特定病变特别具有挑战性，因为与单核苷酸多态性不同，使用聚合酶链反应不可能产生更多含有病变的DNA。因此，需要非常灵敏的检测方法。更广泛的影响。细胞生物学家、毒理学家、药理学家和药物化学家将使用在本研究过程中开发的试剂。此外，利用这些工具来识别DNA损伤生物标志物的潜在用途将直接造福社会，因为它可能检测出基于遗传的疾病，例如在最可治疗的早期阶段的癌症。参与这项研究的本科生、研究生和博士后研究员将接受生物化学、合成有机、物理有机和分析化学方面的广泛培训。此外，他们将通过阅读与DNA损伤及其检测意义相关的背景文献，接触到生物化学方面的重要问题。PI积极参与扩大传统上在化学领域代表性不足的群体的参与。他参与了摩根州立大学化学生物学新本科专业的创建，并参加了各种本科研究研讨会（例如，少数民族学生年度生物医学研究会议），这些群体的成员有很好的代表性。

Oxidative DNA damage is a biologically important and chemically complex process. A large variety (50) of chemical modifications (lesions) are produced when DNA is exposed to oxidative conditions. DNA lesions are associated with aging and the development of disease. Consequently, they are of interest as "biomarkers" to help predict the onset of disease and progression of the aging process. The goal of this project is to develop facile, sensitive chemical methods for detecting lesions in cellular DNA. In addition, the PI will create chemical methods for lesion detection that will be employed by other scientists using commonly available instrumentation and reagents that can be produced by other laboratories and/or commercial suppliers. This chemistry will also enable a determination of whether there is a correlation between specific DNA damage and mutational hotspots. It is particularly challenging to detect specific lesions in telomeres or at exact positions in cellular DNA, because unlike single nucleotide polymorphisms it is not possible to produce more of DNA containing a lesion using the polymerase chain reaction. Hence, a very sensitive detection method is required. Broader Impact. Cell biologists, toxicologists, pharmacologists, and medicinal chemists will use the reagents developed during the course of this research. In addition, the potential use of such tools for identifying DNA lesion biomarkers would benefit society directly by potentially detecting genetically based diseases, such as cancer at an early stage where it is most treatable.The undergraduate students, graduate students, and postdoctoral fellows participating in this research will receive broad training in biochemistry, synthetic organic, physical organic and analytical chemistry. In addition, they will be exposed to biochemically important problems through their reading of the background literature related to DNA damage and the significance of its detection.The PI is actively involved in broadening the participation of groups that have traditionally been underrepresented in chemistry. He has been involved in creating a new undergraduate major in Chemical Biology at Morgan State University, and participates in a variety of undergraduate research symposia (e.g., Annual Biomedical Research Conference for Minority Students) where members of these groups are well represented.