Quantitative analysis of local calcium release across cell types

细胞内钙的释放对肌肉收缩(包括心跳)和卵子(卵母细胞)成熟等功能至关重要。钙释放信号是由细胞内称为“火花”或“气泡”的局部事件启动的，这些事件导致整个细胞的钙释放。该项目将测试控制钙火花和钙喷出的机制是否分别涉及卵母细胞内全细胞钙释放和心肌细胞内钙释放的生理过程，如果不严格控制，这可能会导致心肌收缩不协调(心律不齐)的问题。来自纽约城市大学的本科生将参与这一研究项目，学习细胞生物学的概念和生物过程的数学模型。本科生进行的研究将包括在《教学资源》出版物中，该出版物将广泛提供本科生对此做出重大贡献的教材。需要检验的假设是，泡芙终止机制将促进卵母细胞生理性的、细胞范围的钙释放，而火花终止机制将抑制心肌细胞的病理性细胞范围的钙释放。在这个项目中，将进行模拟，以评估火花和喷发的激活和终止机制如何影响释放地点内和地点之间的事件变异性。还将模拟钙火花、钙喷和从局部事件到细胞范围内钙波的转变之间的关系，并将通过实验(使用非洲爪哇卵母细胞和大鼠心肌细胞)通过测量钙火花、钙喷的可变性以及这如何影响火花/喷到钙波的转变来检验建模预测。

The release of calcium inside cells is critically important for such functions as muscle contraction (including heartbeat) and egg (oocyte) maturation. Calcium release signals are initiated by local events inside cells known as "sparks" or "puffs" and these lead to the release of calcium throughout the cell. This project will test whether the mechanisms that control calcium sparks and puffs are involved respectively in the physiological process of cell-wide calcium release in oocytes and the cell-wide release of calcium in heart cells which, if not tightly controlled, can lead to problems with uncoordinated contractions of heart muscle (irregular heart beat.) Undergraduate students from the City University of New York will be engaged with this research project, learning concepts of both cell biology and the mathematical modeling of biological processes. The studies carried out by undergraduates will be included in a "Teaching Resource" publication that will make widely available teaching materials to which undergraduates have made major contributions. The hypothesis to be tested is that mechanisms of puff termination will encourage physiological, cell-wide Ca2+ release in oocytes whereas spark termination mechanisms will suppress pathological cell-wide Ca2+ release in cardiac myocytes. In this project, simulations will be carried out to evaluate how the mechanisms of activation and termination of sparks and puffs influence event variability within release sites and between sites. The relationships between Ca2+ sparks, Ca2+ puffs, and the transition from local events to cell-wide Ca2+ waves will also be simulated, and modeling predictions will be tested experimentally (using Xenopus oocytes and rat cardiac myocytes) by measuring variability in Ca2+ sparks,variability in Ca2+ puffs, and how this influences the spark/puff to Ca2+ wave transition.