The Tools

Methods and softwares developed in the lab

In the lab
We have developed new methods for probing transcription factor dynamics at the level of single molecule in living cells (Hammar et al. Science 2012). These methods make it possible to study gene regulation directly and at a higher time resolution than methods based on expression of reporter genes.
We are also developing new methods for tracking individual proteins molecules in living cells at ms time resolution (English et al. PNAS 2011).



The optical set-up for single molecule tracking in living cells.

Computational
The Next Subvolume Method (Elf and Ehrenberg, IEE Systems Biology, 2004) is a very efficient method for simulating stochastic reaction diffusion kinetics.  The algorithm is for instance implemented in our MesoRD software (Hattne et al. Bioinformatics, 2005, Fange et al. PNAS 2010). MesoRD has for instance been used to understand the noise induced phenotypes of the E. coli Min system (Fange and Elf PLoS CB, 2006; Fange Bioinformatics 2012).

vbSPT is an analytical tool that uses the information from thousands of short single-molecule trajectories to identify the number of underlying diffusive states as well as the state transition rates. The method is based on a variational Bayesian treatment of hidden Markov models. While other HMMs for diffusing particles use a fixed number of states (most often two or three) and individual long trajectories, the vbSPT method is capable of learning model parameters such as transition rates, as well as the number of diffusive states, from the experimental data. Furthermore, the method is able to extract useful information even from data sets with only a few points per trajectory.

SMeagol SMeagol will help you optimize your experimental set-ups and make sure that there is no bias in your data analysis. The software creates realistic synthetic microscopy images by combining reaction diffusion simulations with simulations of the fluorophore photophyscis and the photophysics of the optical system. SMeagol will be presented in more detail in an upcoming issue of Bioinformatics.

Theoretical
The theory for selective charging of tRNA (Elf et al. Science 2003) explains how the genetic code is used under amino acid limitation.  The theory has now been tested in a number of experimental studies (EMBO rep, 2005, EMBO rep, 2005 JMB, 2005).

The generalization of zero order kinetics to several dimensions (Elf et al. Biophys J, 2003, Genome Res, 2003), that implies that the substrate pools to multi substrate reactions can display huge stochastic fluctuations and ultra sensitivity because the increase in one pool is compensated by the decrease in an other so that the overall flux is conserved. The observation has consequences for the flux of amino acids in protein synthesis (Biophys J, 2005).

New theoretical methods to analyze stochastic processes makes it possible to investigate the consequences of time delays in gene regulatory control circuits (Grönlund et al. PNAS 2009, Nature Communications 2010)