Optimization of passive search processes with application to particle transport and gene regulation in biological cells and diluted solution

该项目涉及复杂的被动搜索过程及其在基因调控和细胞颗粒运输中的优化。这种搜索过程在生物细胞中起着至关重要的作用。我们计划提出分析模型（基于连续时间随机漫步和缩放理论），将与广泛的计算机模拟进行比较。区分了两个子项目：(1)在大多数生化实验中典型的稀溶液中，dna结合蛋白的特定结合位点的熟悉的Berg-von Hippel模型将被推广。特别是，沿着DNA分子的一维扩散（扩散滑翔与微跳）和节段间转移的作用将被研究（与lcv飞行搜索策略的相关性）。(2)在体内条件下，我们将开发颗粒运输和基因调控的新图景。特别是我们想要阐明分子拥挤的状态，以及它是如何引起生物大分子的亚扩散的（以及可能的弱遍历性断裂）。此外，我们计划在定量模型中分析接近退火极限的段间转移的作用。研究了高效搜索优化（最小蛋白数）和遗传控制单元可靠性等问题。

This project deals with complex passive search processes and their optimization in gene regulation and cellular particle transport. Such search processes play a crucial role in biological cells. We plan to come up with analytical models (based on continuous time random walk and scaling theories) that will be compared to extensive computer simulations. Two subprojects are distinguished:(1) In dilute solution typical for most biochemical experiments the familiar Berg-von Hippel model of DNA-binding proteins for their specific binding site will be generalized. In particular, the role of one-dimensional diffusion along the DNA molecule (diffusive gliding versus micro-hops) and intersegmental transfers will be studied (relevance of Lévy flight search strategies).(2) Under in vivo conditions we will develop a new picture of particle transport and gene regulation. Especially we want to shed light on the state of molecular crowding and how it causes the subdiffusion of biomacromolecules (and possibly a weak ergodicity breaking). Moreover, we plan to analyse the role of intersegmental transfers close to the annealed limit in a quantitative model. Questions like search optimization at high efficiency (minimum protein number) and reliability of genetic control units will be studied.