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

这个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（基于连续时间随机游走和标度理论），并将其与广泛的计算机模拟进行比较。本研究分为两个子计画：（1）在稀释溶液中，对于大多数生化实验来说，常见的DNA结合蛋白质的Berg-von Hippel模型将被推广。特别是，一维扩散沿着DNA分子的作用（扩散滑动与微跳）和段间转移（莱维飞行搜索策略的相关性）将被研究。(2)在体内条件下，我们将开发一个新的图片的颗粒运输和基因调控。特别是，我们想阐明分子拥挤的状态，以及它如何导致生物大分子的亚扩散（可能是弱遍历性破坏）。此外，我们计划在定量模型中分析接近退火极限的片段间转移的作用。将研究高效率（最小蛋白质数量）的搜索优化和遗传控制单元的可靠性等问题。

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.