Regulation of transcription elongation
Lead Research Organisation:
Newcastle University
Department Name: Inst for Cell and Molecular Biosciences
Abstract
Transcription elongation is the process of synthesis of RNA on genomic DNA, and is a heavily regulated step of gene expression. Metabolic switches, life style choices, and virulence of bacteria are frequently regulated at the level of transcription elongation, which, not surprisingly, is a potent target for antibiotics. Malfunctions of transcription elongation in human cells are linked to various serious diseases, including cancers, Alzheimer, multiple sclerosis. Therefore, understanding the fundamental mechanisms of transcription elongation and its regulation is essential for intelligent manipulation of pathogenic and biotechnologically important microorganisms, development of new antibiotics and fighting diseases.
However, the molecular mechanisms of regulation of transcription elongation are poorly understood. The project will investigate the following aspects of transcription elongation (i) control of transcription elongation by coupled translation (ii) the mechanisms of transcription pausing and prevention of collisions of RNA polymerase with replication, (iii). influence of transcription elongation factors, small molecule effectors and metal ions on transcription processivity
The project will bring insights into fundamental aspects of regulation one of the most important processes in the cell, and will pave the way for development of new antimicrobials and understanding the basic mechanisms of diseases.
The project consists of 3 proposed interconnected and overlapping stages. The aims will be prioritised or adjusted based on the progress in each of the stage.
Molecular biology techniques include molecular cloning and mutagenesis, microbiological techniques, protein expression and purification, in vitro RNA production; characterisation of RNAP and ribosome activities in transcription and translation in vitro.
The project aligns well with Strategic Priorities Industrial biotechnology and Bioscience for health, as it involves construction of one of the most complex biosynthetic molecular system, which, in the same time, involves several potent targets for antibiotics.
However, the molecular mechanisms of regulation of transcription elongation are poorly understood. The project will investigate the following aspects of transcription elongation (i) control of transcription elongation by coupled translation (ii) the mechanisms of transcription pausing and prevention of collisions of RNA polymerase with replication, (iii). influence of transcription elongation factors, small molecule effectors and metal ions on transcription processivity
The project will bring insights into fundamental aspects of regulation one of the most important processes in the cell, and will pave the way for development of new antimicrobials and understanding the basic mechanisms of diseases.
The project consists of 3 proposed interconnected and overlapping stages. The aims will be prioritised or adjusted based on the progress in each of the stage.
Molecular biology techniques include molecular cloning and mutagenesis, microbiological techniques, protein expression and purification, in vitro RNA production; characterisation of RNAP and ribosome activities in transcription and translation in vitro.
The project aligns well with Strategic Priorities Industrial biotechnology and Bioscience for health, as it involves construction of one of the most complex biosynthetic molecular system, which, in the same time, involves several potent targets for antibiotics.
