Modeling of kinetic processes in biological systems

生物系统动力学过程建模

• 批准号: 7733767
• 负责人: Alexander Berezhkovskii
• 金额: $ 7.76万
• 依托单位: CENTER FOR INFORMATION TECHNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7733767
• 关键词: Biological; Biological Assay; Cell Communication; Cells; Complex; Cultured Cells; Data; Dendritic Cells; Dendritic Spines; Descriptor; Development; Diffuse; Diffusion; Drosophila genus; Embryo; Entropy; Future; Goals; Human; Infection; Interferons; Ion Channel; Ions; Kinetics; Length; Ligands; Modeling; Pathway interactions; Process; Property; Proteins; Rate; Second Messenger Systems; Signal Transduction; Structure; System; Time; Transmembrane Transport; Tube; Universities; Vertebral column; Walking; Work; morphogens; novel strategies; particle; professor; protein folding; research study; response; second messenger; theories

Channel-facilitated membrane transport. (i) We developed a general time-dependent theory of transport through membrane channels. We used the theory to demonstrate that the fluctuation theorem is equally applicable for transport of both interacting and non-interacting particles. (ii) We also worked out the problem of fluctuations of the ion current through a membrane channel due to partial blocking of the channel by translocating molecules. Two-state protein folding. We generalized Kramers-Langer theory of activated rate processes to the case of discrete underlying stochastic dynamics. Application of our theory to folding of two-state proteins allows one to find folding and unfolding rates as well as most probable folding/unfolding pathways. Non-Markovian asymmetric random walks. We suggested a new approach which allowed us to find the Laplace transform of the propagator and related descriptors for non-Markovian asymmetric random walks with and without boundaries. These results were used when developing the general time-dependent theory of transport through membrane channels mentioned above. Cell-to cell communication in cultures of suspended cells. We developed a theory of ligand internalization in cultures of suspended cells, which communicate by diffusing ligands. Our theory shows how the time and length scales characterizing the ligand internalization depend on the properties of the cells and ligands as well as on the parameters of the assay like the cell concentration, etc.. The theory was used to analyze experimental data on Interferon signaling in experiments on early response of cultured human dendritic cells to virial infection. Dynamics of morphogen gradients in the Drosophila Embrio. We analyzed various aspects of the dynamics of different maternal morphogen gradients in the Drosophila Embryo. The goal of our analysis was to rationalize experimental observations made in Professor Shvartsman's Lab. at Princeton University. Transport in porous structures with entropy traps and barriers. We developed theories of diffusion in tubes with periodic entropy traps formed by dead ends and in tubes with periodic entropy barriers formed by contacting spheres. In the future we are going to use these results to analyze compartmentalization of second messengers in dedritic spines.

凝胶促进膜转运。(i)我们开发了一个一般的时间依赖性理论的运输通过膜通道。我们用这个理论证明了涨落定理同样适用于相互作用和非相互作用粒子的输运。(ii)我们还解决了离子流通过膜通道的波动问题，这是由于移位分子部分阻塞了通道。 双态蛋白质折叠本文将Kramers-Langer活化速率过程理论推广到离散随机动力学的情形。应用我们的理论折叠的两个状态的蛋白质，可以找到折叠和展开率以及最可能的折叠/展开途径。 非马尔可夫非对称随机游动我们提出了一种新的方法，使我们能够找到传播子和相关的描述符的拉普拉斯变换的非马尔可夫非对称随机游动的边界和无边界。这些结果被用于开发上述的通过膜通道的运输的一般时间依赖性理论。 悬浮细胞培养中的细胞间通讯。我们发展了一个理论的配体内化培养的悬浮细胞，沟通扩散配体。我们的理论表明，配体内化的时间和长度尺度如何取决于细胞和配体的性质以及细胞浓度等测定参数。该理论被用于分析在培养的人树突状细胞对病毒感染的早期反应的实验中关于干扰素信号传导的实验数据。 果蝇胚胎中形态发生梯度的动力学。我们分析了果蝇胚胎中不同母体形态发生梯度动态的各个方面。我们分析的目的是使Shvartsman教授实验室的实验观察合理化。在普林斯顿大学。 具有熵陷阱和势垒的多孔结构中的输运。我们发展了管中的扩散理论与周期性熵陷阱形成的死端和在管中的周期性熵障碍形成的接触球。将来我们将利用这些结果来分析树突棘中第二信使的区室化。