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

• Applicant: Professor Dr. Ralf Metzler
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: from 2008 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 73110949

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.

• DFG Programme: Research Grants