The goal is to understand the mechanisms of termination of protein synthesis, recycling of ribosomes from termination back to initiation, initiation of protein synthesis, elongation of proteins, accuracy of tRNA and release factor selection by the messengerRNA coded ribosome, toxicity of mini-genes and drop-off of peptidyl-tRNA. We use quantitative biochemical methods in combination with molecular genetics and experiments on living bacteria. Future directions include studying mechanisms for protein export and structural analysis of important, functional ribosome-factor complexes.
Protein synthesis in biotechnology
The goal is to constitute an in vitro system for bacterial protein synthesis which can be used to (i) produce any conceivable protein in large scale starting from its gene sequence (ii) synthesise proteins which are isotope labelled in chosen regions to facilitate structural analysis with NMR (iii) develop new, powerful techniques for combinatorial design of oligo-peptides and proteins and apply these methods to obtain new antibiotics, new protein biosensors and new catalysts.
The Ehrenberg lab is actively exploring a number of topics in the area of Systems Biology.
- Stochastic modelling of copy number control for plasmids, with special reference to plasmids ColE1 and R1. The focus has been on how plasmids can achieve precise control of copy numbers to minimize plasmid losses at cell division also when their average copy numbers per cell are small.
- General features of noise in intracellular control systems. This area includes hyper-fluctuations in intracellular chemical reactions which operate near criticality and a suggestion, stochastic focusing, for how noise can enhance, rather than reduce sensitivity in molecular control systems.
- Regulation of protein synthesis, adaptation and growth control in bacteria. This area deals with how bacteria with the help of local control systems for regulation of gene expression (e.g. repressors and attenuation of transcription) in combination with global control systems (e.g. the stringent response to amino acid starvation) can grow fast in different media and adapt rapidly to environmental changes. Theoretical modelling and experimental approaches are combined.
- Action of antibiotics and mechanisms for antibiotic resistance in bacteria (in collaboration with Tanel Tenson, Tartu). This work is primarily dealing with the action of macrolides on bacterial protein synthesis and descriptions of a number of resistance mechanisms against these drugs. Theoretical modelling and experimental approaches are combined.
- Development of numerical methods for stochastic descriptions of intracellular reaction-networks including diffusion-reaction couplings (in collaboration with Per Lötstedt, Scientific Computing, Uppsala University). This work is dealing with developments of efficient algorithms for numerical solutions of the master equation in intracellular chemical networks. It also concerns descriptions of diffusion-reaction couplings in macroscopically bistable systems.
In collaboration with
- Tanel Tenson, Tartu University, Estonia. Group leader
- Per Lötstedt, Uppsala University, Sweden. Group leader
- Otto Berg, Uppsala University, Sweden. Emeritus
- Hans Bremer, University of Dallas, Texas, USA. Emeritus
- Zoya Ignatova, University of Hamburg, Germany. Group leader