Time resolved studies of transport in renal epithelial cells

描述(由申请人提供)： 我的教育背景是物理学(理学士和理科硕士)和材料工程(PHD)。在过去的五年里，我的学术研究一直专注于弹道电子传输和微流体。我建造了一个微型制造的微流体传感器来实时测量细胞体积，这个项目引起了我对生物医学科学的兴趣。我的直接目标是接受生物学方面的培训，这样我就可以成为肾脏生物物理学的独立研究员。我的长期目标是将我的物理和材料科学知识应用于肾脏，希望为治疗肾脏疾病做出贡献。 我目前的生物学知识来自于自我教育，因此相当狭隘。我想要一个更正式的培训，包括授课课程、实验室实践经验和参加科学会议。我将在弗雷德里克·萨克斯博士的指导下做肾细胞体积调节的研究。萨克斯博士是细胞生物物理学，特别是机械转导方面的专家。在他的指导下，我将研究肾脏细胞如何应对渗透和化学挑战的生物物理学。这项研究将使用新的体积传感器芯片。 我在这个项目中有五个具体目标：1)优化传感器的技术，以实现最小的液体交换时间、温度调节和稳定性；2)测量培养的肾上皮细胞体积调节的动力学；使用荧光显微镜将体积变化与细胞内离子浓度相关联；3)使用特定的药物干预将溶质和水通量分成不同的组分；4)研究与多囊肾病特别相关的肾小管液体流动和切应力对上皮细胞体积的影响；以及5)建立体积调节的数学模型，以从数据中提取物理相关参数。

DESCRIPTION (provided by applicant): My educational background is in physics (B. S. and M.S.) and materials engineering (PhD). My academic research over the last five years has been focused on both ballistic electron transport and microfluidics. I built a microfabricated microfluidic sensor to measure cell volume in real time, and this project caused me to become interested in biomedical sciences. My immediate goal is to train in biology so I may become an independent researcher in kidney biophysics. My long-term goal is to apply my knowledge of physics and materials science to the kidney and hopefully to make a contribution to treating kidney diseases. My current knowledge of biology has come from self-education and is thus rather narrow. I want a more formal training with didactic courses, hands-on laboratory experience and attendance at scientific meetings. I will do research on the regulation of renal cell volume with Dr. Frederick Sachs as mentor. Dr. Sachs is an expert in biophysics of cells, particularly mechanical transduction. Under his guidance I will study the biophysics of how renal cells respond to osmotic and chemical challenges. The research will use the new volume sensor chip. I have five specific goals in this project: 1) optimize the technology of the sensor for minimal fluid exchange time, temperature regulation and stability, 2) measure the dynamics of cell volume regulation in cultured renal epithelial cells; correlate the volume changes with the concentration of intracellular ions using fluorescence microscopy, 3) partition the solute and water flux into separate components using specific pharmacological interventions, 4) to examine the effect of tubular fluid flow and shear stress on epithelial cell volume with particular relevance to polycystic kidney disease, and 5) to build mathematical models of volume regulation to extract physically relevant parameters from the data.