Newly synthesised proteins must attain the correct three-dimensional conformation in order to function. Understanding how polypeptides fold in cells remains a fundamental question in biology and is of great importance to the biotechnology industry which manufactures therapeutic proteins such as monoclonal antibodies, hormones and growth factors. The kinetics of messenger RNA translation is emerging as a novel mechanism to regulate the fate and folding of newly synthesised polypeptides. The redundancy of the genetic code means that most amino acids are encoded by multiple ‘synonymous’ codons, each of which can be translated into the same amino acid but at different rates. It has been suggested that the use of ‘fast’ and ‘slow’ translating codons may promote accurate folding by regulating the speed with which the polypeptide is synthesised. The aim of this project is to investigate the role of codon use in promoting efficient production of membrane and secretory proteins, with a view to defining the global rules linking codon choice to efficient folding. This will be achieved through a combination of computational (bioinformatics) and wet laboratory (molecular biology, cell biology, biochemistry) approaches. As a result, the student will develop a wide range of skills in bioinformatics, molecular and cell biology, and protein biochemistry.
This project is to be funded under the BBSRC Doctoral Training Programme. Projects under this scheme are competitively funded; ie there are more projects advertised than are available. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form, full details on how to apply can be found on the BBSRC DTP website http://www.dtpstudentships.manchester.ac.uk/