Mechanisms controlling cell wall biosynthesis in Streptococcus pneumoniae FULLY FUNDED

Pneumonia and meningitis are leading causes of human morbidity and death in the world. One of the most common organisms responsible for these diseases is the bacterium Streptococcus pneumoniae. Like many bacteria, S. pneumoniae cells are surrounded by a cell wall which provides their characteristic shape and protects the cells from lysis. The cell wall is synthesised by large multi-enzyme complexes whose activity is tightly controlled and coupled to cell growth. Antibiotics used to treat S. pneumoniae infections target these enzymes compromising the structure of the wall leading to cell death. Worldwide antimicrobial resistance is a huge challenge to human health and new strategies which target the cell wall are urgently needed. Further insight into how the cell wall is synthesised will lead to future novel targets for treatment strategies.

Remarkably little is known about how the cell wall is synthesised given its importance as a drug target. However, recent studies have identified key enzyme activities required to build the cell wall and previous work from the lab has characterised a new regulator of the cell wall building enzymes in S. pneumoniae.

The project will use deep sequencing approaches (Tn-seq/Mut-seq) to reveal relationships between genes involved in cell wall biosynthesis. Once identified, further genetic screens, biochemical assays and epifluorescence microscopy will be used to understand the fundamental mechanisms by which these cells grow and divide.