Tidsperiod: 2013-01-01 till 2018-12-31
Budget: 18 000 000 SEK
The overall ambition is to make intracellular measurements that bridge the gap between quantitative physical models and biological observations in order to identify and resolve inconsistencies in our current understanding of life at the molecular level. We are particularly interested in how key steps in transcription, translation and replication are regulated in the intracellular environment and at what level of physical detail these processes need to be modeled to describe their function in the living cell. Examples of specific questions include how RNA polymerases have evolved to rapidly find and bind promoters, how DNA replication is coordinated with cell growth, how cells can filter out leakage during replication of repressed genes and how fast individual ribosomes translates specific transcripts. Answering these questions requires better methods to study intracellular kinetics at high spatial and temporal resolution. For this purpose we develop single-molecule methods to probe kinetics with minimal perturbation of the cell, and accurate tools for computational modeling of intracellular biophysics, considering specific complications such as stochasticity, diffusion limited chemical reactions and confined geometries. Overall the project is unique in its ambition to make a physically consistent quantitative description of life at the molecular level.