Fundamental Understanding of Growth and Inhibition of Calcium Oxalate Kidney Stones

非技术性：数以百万计的美国人患有肾结石和相关疾病。目前，肾结石的形成、成分和生长所涉及的科学尚不清楚。因此，没有成熟的治疗方法，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经常有类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。这些晶体从原子尺度开始经历成核和生长，并发展到毫米或厘米尺度。大多数可用的治疗方法都是为了解决通过标准成像技术可以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，很难分解或溶解。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，以及不同晶体结构形成的机制，可以提供线索，为什么一些药物只对一些肾结石患者有效。拟议的高级显微镜研究可以为肾结石的形成和生长提供洞察力，如果这项研究成功，这些研究的科学反过来可以开发新的预防和治疗方案。此外，这些材料研究在聚合物、制药、食品、地球科学和光电材料等其他对晶体形成和生长至关重要的科学中将是非常宝贵的。在这项研究的过程中，将特别注意招募和指导女学生和代表性不足的学生在主要调查人员的研究实验室工作。此外，该项目的研究成果将被纳入相关的本科生和研究生班级，以进一步激发具有基础知识的新一代学生从事这一领域。为了提高公众的认识，PIS计划通过社交媒体、新闻报道和新闻发布来传播这一项目的新成果。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。这种疾病在美国大约有2000万人受到影响。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是如何形成的以及如何防止这些矿物的生长有更根本的了解。使用亚纳米级分辨率的液体电子显微镜，这个项目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使用最先进的象差校正透射电子显微镜监测局部化学和结构演变，该显微镜配备了对单个原子敏感的成像和光谱仪。这项研究有望对不同环境条件下钙晶体的生长动力学有一个新的认识。这些研究的更广泛的科学影响可能有助于进一步了解聚合物、药品、食品、地球科学和光电材料的晶体形成和生长。该奖项在推广活动方面的更广泛影响将是将本科生和研究生纳入关于最先进的显微技术用于提高生活质量的卫生科学的培训和教育。作为计划的外展活动的一部分，少数族裔和代表性不足的学生将参加科学访问和实验室活动的实践经验。这项研究的发现将被纳入生物工程研究生课程，该课程已为高年级本科生和研究生开发。PIS致力于通过伊利诺伊大学芝加哥分校成熟的外展项目招收女性/少数族裔学生接受本科教育。

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.