Fundamental Understanding of Growth and Inhibition of Calcium Oxalate Kidney Stones

非技术性：数百万美国人患有肾结石和相关疾病。肾结石的病因有哪些？肾结石的病因有哪些？因此，没有很好的治疗方法，以及如何防止它们的形成和生长。目前使用不同抑制剂预防这种疾病的治疗方法在通常具有相似症状的患者中显示出不一致的结果。草酸钙（CaOx）晶体是肾结石的主要成分。这些晶体经历从原子尺度开始的成核和生长，并进展到毫米或厘米尺度。大多数可用的治疗方法旨在解决可以通过标准成像技术检测到的晶体的存在。在晶体生长的这个阶段，这些晶体变得非常稳定，难以分解或溶解。拟议的研究旨在了解晶体成核和生长所涉及的科学，目的是了解这些晶体在纳米尺度上的化学和物理变化。了解CaOx的纳米级结晶，以及形成不同晶体结构的机制，可以为为什么一些药物只能有效治疗某些肾结石患者提供线索。拟议的高级显微镜研究可以深入了解肾结石的形成和生长，如果这项研究成功，这些研究的科学可以反过来开发新的预防和治疗方案。此外，这些材料研究在晶体形成和生长至关重要的其他科学中也是非常宝贵的，例如聚合物，制药，食品，地球科学和电光材料。在这项研究过程中，将特别注意征聘和指导女学生和代表性不足的学生在主要研究者的研究实验室工作。此外，本项目的研究成果将纳入相关的本科生和研究生课程，以进一步激发新一代具有基础知识的学生从事这一领域。为了提高公众意识，PI计划通过社交媒体、新闻报道和新闻稿传播该项目的新成果。技术：该项目的目标是更好地了解导致肾结石疾病的草酸钙（CaOx）矿物形成机制的基础科学。这种疾病影响了美国大约2000万人。目前的治疗方法对这些患者的结果不一致，这表明必须对这些晶体如何形成以及如何防止这些矿物质的生长获得更基本的了解。利用具有亚纳米尺度分辨率的液体电子显微镜，该程序将研究草酸钙晶体在液体溶液中的形成。这项研究的一个独特优势是能够监测当地的化学和结构的演变与国家的最先进的像差校正透射电子显微镜配备成像和光谱仪敏感的单原子。该研究有望对钙晶体在不同环境条件下的生长动力学有新的认识。这些研究的科学影响可能有助于进一步了解聚合物、药物、食品、地球科学和电光材料的晶体形成和生长。该奖项对外联活动的更广泛影响是将本科生和研究生纳入关于健康科学最先进显微技术的培训和教育，以改善生活质量。作为计划外展活动的一部分，少数民族和代表性不足的学生将被纳入科学访问和实验室活动的实践经验。这项研究的结果将被纳入一个生物工程研究生课程，已开发的高年级本科生和研究生。PI致力于通过芝加哥伊利诺伊大学完善的外展计划招募女性/少数民族学生接受本科教育。

Non-Technical:Millions of Americans are afflicted by kidney stones and related diseases. Currently the sciences involved in the formation, composition and growth of kidney stones are not known. Hence, there are no well developed treatments, and how to prevent their formation and growth. Current treatments for the prevention of this disease using different inhibitors show inconsistent results among patients who often have similar symptoms. Calcium oxalate (CaOx) crystals are the main constituents of kidney stones. These crystals undergo nucleation and growth starting from atomic scale, and progresses to millimeter or centimeter scales. Most of the available therapeutic treatments are designed to address the presence of crystals that may be detected through standard imaging techniques. At this stage of the crystal growth, these crystals become very stable and are difficult to breakdown or dissolve. The proposed research aims to understand the sciences involved in the nucleation and growth of crystals with the goal to understand the chemical and physical changes to these crystals at nanoscales. Understanding the nanoscale crystallization of CaOx, and the mechanisms through which different crystal structures are formed could provide clues why some medications are effective in treating only some kidney stone patients. The proposed advanced microscopic studies could provide insight into kidney stone formation and growth, and sciences from these studies could in turn develop novel prevention and treatment protocols, if this research is successful. Additionally, these materials research studies would be invaluable in other sciences for which crystal formation and growth are critical, such as polymers, pharmaceuticals, food products, geosciences and electro optic materials. Through the course of this research, particular attention will be given in recruiting and mentoring female and underrepresented students to work in the principal investigators' research laboratory. In addition, the research findings of this project will be incorporated in relevant undergraduate and graduate classes to further stimulate a new generation of students with the fundamental knowledge to engage in this field. To increase public awareness, the PIs plans to disseminate the new results of this project through social media, press coverage, and news releases.Technical:The goal of this project is to gain a better understanding of the basic sciences in the formation mechanisms of calcium oxalate (CaOx) minerals that are responsible for kidney stone disease. This disease affects approximately 20 million people in the United States. The current treatments show inconsistent results for these patients indicating that more fundamental understanding must be gained on how these crystals formed and how one can prevent the growth of such minerals. Using liquid electron microscopy with subnanometer scale resolution, this program will study the formation of calcium oxalate crystals in liquid solution. A unique advantage of this study is the ability to monitor the local chemical and structural evolutions with the state-of-the art aberration-corrected transmission electron microscopy equipped with imaging and spectrometers sensitive to single atoms. The proposed research is expected to yield a new understanding on the growth kinetics of Calcium crystals under different environmental conditions. The scientific broader impact of these studies could benefit further understanding in crystal formation and growth of polymers, pharmaceuticals, food products, geosciences and electro optic materials. The broader impacts with respect to outreach activities of this award would be the inclusion of students at both undergraduate and graduate level in training and education on the state-of-the art microscopy techniques for health sciences in improving the quality of life. As part of the planned outreach activities, minority and underrepresented students will be included for scientific visits and hands-on experience in the lab activities. The finding of this research will be incorporated in a bioengineering graduate course that has been developed for senior undergraduate and graduate students. The PIs are committed to recruit female/minority students for undergraduate education through well-established outreach programs at the University of Illinois at Chicago.