About the Project
Despite the availability of vaccines and antibiotics, infectious diseases are still one of the major causes of death, killing millions of people around the world. In order to develop new tools to fight these diseases research to understand how bacteria cause infectious disease is vital. Research in this area mainly has concentrated on traditional virulence factors such as toxins. We are taking a different approach, namely the role of bacterial metabolism in disease.
Streptococcus pneumoniae is a major cause of blood poisoning, ear infections and pneumonia, as well as meningitis. Previously we showed that nutrient metabolism is an important determinant of the virulence of this pathogen, so that now we can offer a range of projects aimed at understanding the details that explain how bacterial metabolism is important during disease.
One example of the projects we offer is based on the metabolism of sugars by S. pneumoniae. Most studies have used glucose to understand pneumococcal metabolism but in the respiratory tract the main available sugar is galactose. We showed that when galactose is used as nutrient, the pneumococcus changes its metabolism and if the enzymes involved in galactose metabolism are absent, the pneumococcus is weakened in virulence, presenting these enzymes as potential targets for new drugs against the pneumococcal diseases. Additionally, the metabolite end products have major influences on the response of the host to infection. The role of metabolism of other sugars, such as mannose and fucose, and their metabolite end products, such as acetate and lactate, has not been studied in detail. Therefore, projects will be within the broad scope of investigation of pneumococcal metabolism of sugars and virulence, as well as in studying the role of metabolite end products on the pathophysiology of pneumococcal infection.
In your project, you will be trained in techniques in bacteriology, biochemistry, molecular biology, cell culture and in vivo models of disease. Some of the specific techniques may include targeted mutations, real time PCR, quantitative RT-PCR, enzyme and metabolic end product analysis, expression and purification of microbial proteins, ELISA, routine maintenance of cell culture and related assays, and in vivo models of disease.
We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups.
References
1: Terra VS, Homer KA, Rao SG, Andrew PW, Yesilkaya H. Characterization of novel beta-galactosidase activity that contributes to glycoprotein degradation and virulence in Streptococcus pneumoniae. Infect Immun. 2010 Jan;78(1):348-57.
2: Yesilkaya H, Spissu F, Carvalho SM, Terra VS, Homer KA, Benisty R, Porat N, Neves AR, Andrew PW. Pyruvate formate lyase is required for pneumococcal fermentative metabolism and virulence. Infect Immun. 2009 Dec;77(12):5418-27.
3: Yesilkaya H, Manco S, Kadioglu A, Terra VS, Andrew PW. The ability to utilize mucin affects the regulation of virulence gene expression in Streptococcus pneumoniae. FEMS Microbiol Lett. 2008 Jan;278(2):231-5.
4: Yesilkaya H, Soma-Haddrick S, Crennell SJ, Andrew PW. Identification of amino acids essential for catalytic activity of pneumococcal neuraminidase A. ResMicrobiol. 2006 Jul-Aug;157(6):569-74.