Chiral sum frequency generation spectroscopy for characterization of DNA secondary structures

DNA具有标志性的双螺旋结构和众所周知的存储遗传信息的功能。然而，最近的研究表明，DNA可以采用双螺旋结构以外的构象，这些构象的DNA可以参与信号传导过程，调节基因表达，从而指导生物系统生存的细胞过程。化学系的生命过程化学项目资助耶鲁大学的Elsa Yan博士开发一种区分DNA不同构象的新方法，称为手性和频率产生光谱。该方法相对于现有的方法，如核磁共振波谱、x射线晶体学和线性光谱学具有优势，因为它具有高选择性和低背景，并且可以实时检测少量的DNA。鉴于这些优势，该方法可以提高我们制定涉及各种DNA构象的规则的能力，以预测响应环境变化（例如，损伤和感染）或细胞发育需求（例如，衰老和细胞分裂）的生物行为。该项目还包括旨在促进耶鲁大学包容性学习的教育活动，耶鲁大学的学生群体越来越多样化。在非科学专业的化学课程中实施了旨在帮助代表性不足的少数民族学生取得成功的教学策略；教育专家对其有效性进行了评估。该项目还包括参与一项针对当地小学生的科学推广计划，旨在激发学生对化学和一般科学的兴趣。该项目寻求使用手性振动和频率产生光谱来识别振动特征，可以用来明确地解决各种DNA二级结构。该项目侧重于涉及基因表达调控的DNA二级结构，如g -四联体和i-motif。然后用振动特征来检查DNA二级结构和化学修饰之间的关系。该项目研究了各种DNA序列和构型中核碱基的氧化如何扰乱DNA的二级结构。这些结果用于评估DNA氧化损伤对基因表达和功能的影响。该项目有望建立一种表征DNA二级结构的新方法，并通过DNA二级结构的变化机制提高我们对DNA调控基因表达的认识。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

DNA has a signature structure of a double helix and the well-known function of storing genetic information. However, recent studies have revealed that DNA can adopt conformations other than that of a double helix, and DNA in these conformations can participate in the signaling process to regulate gene expression, and thereby direct cellular processes for survival of biological systems. The Chemistry of Life Processes Program in the Division of Chemistry is funding Dr. Elsa Yan from Yale University to develop a new method for distinguishing various conformations of DNA, which is named chiral sum frequency generation spectroscopy. This method has advantages over existing methods, such as NMR spectroscopy, X-ray crystallography, and linear optical spectroscopy, because it has high selectivity and low background, and it allows the real-time detection of small amounts of DNA. Given these advantages, the method may improve our ability to formulate rules involving various DNA conformations for forecasting biological behavior in response to changes in environment (e.g., injury and infections) or needs of cellular development (e.g., aging and cell splitting). The project also includes education activities meant to promote inclusive learning at Yale University, where the student body has become increasingly diverse. Pedagogical strategies seeking to help under-represented minority students to succeed are implemented in a chemistry course for non-science majors; their effectiveness is assessed by education experts. The project also includes participation in a science outreach program for local grade-school students that aims to spark student interest in chemistry and the sciences in general. The project seeks to use chiral vibrational sum frequency generation spectroscopy to identify vibrational signatures that can be used to unambiguously resolve various DNA secondary structures. The project focuses on DNA secondary structures that are implicated in the regulation of gene expression, such as G-quadruplexes and i-motifs. The vibrational signatures are then used to examine the relationship between DNA secondary structures and chemical modifications. The project examines how the oxidation of nucleobases in various DNA sequences and configurations perturb the secondary structure of the DNA. The results are used to evaluate the impact of DNA oxidative damage on gene expression and function. The project is expected to establish a new method for characterizing DNA secondary structures and improve our understanding of how DNA regulates gene expression through the mechanism of changes in DNA secondary structures.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.