We investigate how Salmonella infect the human host and survive in the different body compartments and the environment. We have characterised the global population structure of Salmonella typhi and other invasive Salmonella such as the S. Typhimurium ST313, which is found extensively in Africa. We have mapped the global spread of antibiotic resistance in these organisms and use high throughput imaging alongside genetic analysis to link genotype to phenotype in these pathogens. See https://www.perkinelmer.com/uk/libraries/CST_BacterialPhenotyping-GordonDougan
We work in the global health field working on real disease in endemic setting.We have been involved in mapping the spread of extensively resistant (XDR) Salmonella Typhi which emerged in Pakistan and has now spread within the country and beyond. XDR typhoid is very difficult to treat as it is resistant to most cheap and commonly used antibiotics. The Pakistan government has introduced the use of a Vi conjugate typhoid vaccine across the country to try to combat the disease. We are also evaluating Vi-conjugates as part of our work with the THECA consortium in DR Congo, Ghana and Madagascar. We have other projects on typhoid surveillance and schistosome vaccination in Kenya, Burkina Faso and Madagascar.
We manage the Antimicrobial Resistance theme of the Cambridge NIHR Biomedical Research Centre. Here we work closely with clinical groups to develop methods for interrogating clinical sample using multiplex (pathogen/microbiota/host) approaches to extract thousands of data points. We have worked with lung, blood and other samples. Working with the hospital ICU we have investigated the causes of ventilator-associated pneumonia in over 100 patients monitoring pathogen burden, microbiota and host response (e.g. RNASeq analysis). Our data is returned within hours to the bedside and has influenced antibiotic usage and stewardship, influencing hospital practice.
We use stem cells to create models of infection. We can start with either stem cells derived from a tissue e.g. gut or from Induced Pluripotent Stem Cells (IPS cells). IPS cells can be generated from any individual including those harbouring common or rare genetic variants. We also have reference stem cell lines where we or our collaborators have generated mutations in specific genes.
Once we have the stem cells we have protocols for differentiating them into different cell types e.g. macrophages or organoids e.g. intestinal. We can then explore the properties of these cells as they interact with pathogens such as Salmonella. We have systems for microinjecting pathogens into organoids.
To investigate how these organisms infect their host we utilise cellular models largely based on IPS stem cells, which we differentiate into immune cells such as macrophages or organoid systems including gallbladder and intestinal forms. We exploit CRISPR-Cas9-type approaches to create mutant cell lines or develop libraries for screening. We use informatic analysis to identify key host genes that influence pathogenicity and disease outcome.
We have a project with Hong Kong University to exploit modified human stem cells to investigate immune diseases and to develop novel therapies. This work is funded by the Hong Kong Government.
We have funding, in collaboration with the International Vaccine Institute, through the EU and other sources to deploy vaccines in the field. We have projects active in several countries including Madagascar, Kenya and DR Congo working on surveillance and vaccine deployment for typhoid.
tSIte visiit to the new CL3 facility being build at the INRB laboratories in Kinshasa, DR Congo
The Board and management team of The Hilleman Laboratories
Running a genomics and vaccine training course in Karachi, Pakistan
The Board of the International Vaccine Institite