Collaborative: Modeling of Calcium Signaling Differentiation During Oocyte Maturation

Peter Jung和Khaled MachacaProposals IOS-0744798和-0744581协作：卵母细胞成熟过程中钙信号分化的建模一个独特的机会，提供新的方法来理解最重要的细胞信号系统之一，钙信号的发育方面，已经从计算生物物理实验室和细胞生物学实验室之间的相互作用中发展起来。 钙信号的概念是指游离胞质钙离子的瞬时增加。 Ca 2+信号跨越广泛的空间和时间尺度，这赋予它们诱导确定的细胞功能所需的特异性。 例如，通过血管平滑肌中的ryanodine受体的局部Ca 2+释放导致松弛，而全局持续的Ca 2+信号导致收缩。然而，在发育过程中实现信号特异性的分子机制仍然知之甚少。虽然这一研究领域到目前为止主要由细胞和分子生物学方法驱动，但该项目将增加一套新的工具-从纳米到毫米尺度的数学和计算建模-可以为探索复杂的细胞内Ca 2+信号网络在发育过程中的变化提供新的场所。就科学更广泛的影响而言，这项工作的结果将对各种细胞类型产生影响，因为钙信号无处不在，并调节过多的细胞功能，包括神经递质释放，平滑肌细胞收缩和受精。这项工作的跨学科性质增强了该项目的教育广泛影响。 该项目将促进本科生、研究生和博士后的跨学科培训。来自两个不同机构的不同职业水平的学员将获得数学和实验方法方面的专业知识。

Peter Jung and Khaled MachacaProposals IOS-0744798 and -0744581Collaborative: Modeling of Calcium Signaling differentiation during Oocyte maturationA unique opportunity to offer novel approaches toward the understanding of developmental aspects of one of the most important cellular signaling systems, calcium signaling, has developed from the interaction between a computational biological physics laboratory and a cell biology laboratory. The notion of a calcium signal refers to a transient increase of free cytosolic calcium ions. Ca2+ signals span a wide range of spatial and temporal scales, which endow them with the specificity required to induce defined cellular functions. For example, localized Ca2+ release through ryanodine receptors in vascular smooth muscle leads to relaxation, whereas global sustained Ca2+ signals lead to contraction. The molecular mechanisms, however, by which signaling specificity is achieved during development remain poorly understood. While this field of research has been driven so far predominantly by methods of cellular and molecular biology, this project will add a new set of tools - mathematical and computational modeling from the nanometer to the millimeter scale - that can offer new venues to explore changes in the complex intracellular Ca2+ signaling network during development. In terms of scientific Broader Impacts, the results from this work will have implications for a large variety of cell types since calcium signals are ubiquitous and regulate a plethora of cellular functions including neurotransmitter release, contraction of smooth muscle cells and fertilization. The educational Broader Impacts of this proejct are enhanced by the interdisciplinary nature of the work. The project will foster interdisciplinary training of undergraduates, graduate students and postdocs. Trainees at different levels of their career from two different institutions, will acquire expertise in both mathematical and experimental approaches.