Popular Science Presentation
The ribosome and its helping factors constitute the efficient machinery by which the cells construct all the proteins needed in life, both as simple unicellular organisms and as parts of complex multicellular organisms such as humans. The ribosomes are composed of two subunits, the small and the large subunit. The ribosomes link amino acids into long peptide chains, and the amino acid sequences determine the structures that the chains fold into, which in turn determine the function of the proteins in the cell.
The sequences of the peptide chains are coded in the genes in the DNA. In the process called transcription, RNA polymerase transcribe the information from the genes to messenger RNA (mRNA), which is positioned between the two subunits of the ribosome at the initiation of protein synthesis and read by the ribosome in order to construct a correct peptide chain.
Each amino acid is chemically associated with one or more transport RNAs (tRNAs). They arrive at the ribosome in complex with the helping protein EF-Tu and decode the mRNA so that the amino acids are inserted in the correct order in the peptide chain. When an amino acid is incorporated in the peptide chain, the mRNA and tRNA with the aid of the helping protein EF-G are moved, or translocated, backwards by one code word within the ribosome, so that a new tRNA with a new amino acid can enter the ribosome and be linked to the growing peptide chain. This continues until the peptide chain is finished, and released from the ribosome using two termination factors. The ribosome is then recycled by separation of the two subunits so that it may translate the next protein. Again, the factor EF-G assists, together with the ribosomal recycling factor (RRF).
In our research we study every step of this entire process, mainly for bacterial protein synthesis but also some translation factors from eukaryotes (the evolutionary group that includes humans). The transcription of mRNA from DNA is described by mathematical models, in order to understand how the RNA polymerase can synthesize mRNA with the very high precision that has been observed. The initiation of protein synthesis and the repeated elongation of the peptide chains are studied using methods of biochemistry. A great interest of our group is how accurately the tRNAs can decode the mRNA, how this accuracy is achieved and how it improves or worsens by mutations, antibiotics or the surrounding conditions.
We are also interested in how the other processes of protein synthesis, such as initiation, translocation, termination and recycling, can be so fast and accurate. Previously, these processes could only be studied by “freezing” the ribosomes of the desired conformation, but the frozen complexes do not correspond to the authentic, functional complexes in the kinetic progress of the ribosomal functions. One solution is cryo-electron microscopy, which we utilize in collaboration with Columbia University, NY, USA. In another collaboration, with the University of Hamburg, we use a method to detect the position of ribosome on the mRNA in order to study the effect of antibiotics on translocation and recycling. We also use mathematical models and stochastic simulations to study the effect control systems of gene expression of growing bacteria, and how the control systems are affected by antibiotics.