Molecular cross-talk between copper and zinc resistance in pathogenic bacteria

Group B Streptococcus (GBS) is an effective pathogen of humans and animals and is well known as the leading cause of often-fatal infections in newborn infants. Little is known about how GBS resists the immune system and colonises to cause invasive disease.

This PhD will develop a new understanding of how streptococci resist intoxication by metals, a major antimicrobial effector of the human innate immune system. It will investigate how GBS controls a network of genes to counteract toxicity of zinc (Zn) and copper (Cu) when in excess. You will join energetic and well-resourced labs working at the forefront of this field and there will be collaborative opportunities with international experts in the medical microbiology discipline.

Expert multidisciplinary training will be provided in a wide array of advanced bacteriological, molecular, analytical and biochemical techniques to examine metal resistance mechanisms and characterise metabolic pathways in bacteria, e.g. genetic manipulation and generation of knockout mutations.

You will make extensive use of cutting-edge sequencing technologies to study gene structure and function in GBS and use relevant models of disease. The specific focus can be tailored to your interests and you will be involved in all aspects of the study design, with access to outstanding research facilities across the Norwich Research Park and beyond. You will discuss your findings at weekly team and supervisory meetings where your training needs will be developed. You will have opportunities to present work at (inter)national conferences providing opportunities for networking with other scientists.

Your studies will be supervised by Dr Matthew Sullivan in the School of Biological Sciences at UEA in collaboration with Prof Mark Webber at the Quadram Institute and Associate Professor Andrew Gates.

We are seeking a highly motivated applicant with strong interests in molecular microbiology and infectious diseases. Informal enquiries are welcome (matthew.sullivan@uea.ac.uk)

References

Sullivan, M. J., Goh, K. G. K., Ulett, G. C. (2022) Regulatory cross-talk supports resistance to Zn intoxication in Streptococcus. PLoS Pathogens 18(7), e1010607

Goh, K. G. K., Ulett, G. C., Sullivan, M. J. (2022) The Copper Resistome of Group B Streptococcus Reveals Insight into the Genetic Basis of Cellular Survival during Metal Ion Stress. Journal of Bacteriology 204(5)e0006822

Sullivan M. J., Prince D., Goh K. G. K., Katupitiya L., Gosling D., Crowley M. R., Crossman D. K., Ulett G. C. (2023) Dual RNA sequencing of group B Streptococcus-infected human monocytes reveals new insights into host-pathogen interactions and bacterial evasion of phagocytosis. Scientific Reports 13(1):2137

Sullivan, M. J., Goh, K. G. K., Ulett, G. C. (2021) Cellular Management of Zinc in Group B Streptococcus Supports Bacterial Resistance against Metal Intoxication and Promotes Disseminated Infection. mSphere 6(3)e00105-21

Varghese B. R., Goh K. G. K., Desai D., Acharya D., Chee C., Ulett G. C., Sullivan M. J. (2023) Variable resistance to zinc intoxication among Streptococcus agalactiae reveals a novel IS 1381 insertion element within the zinc efflux transporter gene czcD. Fronteirs in Immunology 14:1174695