Gad Frankel is Professor of Bacterial Pathogenesis at the Department of Life Sciences and the MRC Centre for Molecular Bacteriology and Infection (CMBI) at Imperial College London. In 2016, he was awarded a Royal Society International Collaboration Award, funded through the Global Challenges Research Fund, for a collaboration with Professor Sandhya Visweswariah from the Indian Institute of Science (IISc) in Bangalore.
What attracted you to the Royal Society International Collaboration awards?
The UK Government established a £1.5 billion Global Challenges Research Fund to support cutting-edge research that addresses the challenges faced by developing countries. This announcement had a major impact on facilitating collaborations between scientists in the UK and those based in low and medium income countries.
At the MRC centre for Molecular Bacteriology and Infection (CMBI) at Imperial College we identified The Indian Institute of Science (IISc) in Bangalore as an ideal strategic partner to address the current global challenges we face in fighting bacterial infections, including the growing threat from the spread of antimicrobial resistance and the on-going high burden of diarrhoeal diseases, particularly in young children. In one-on-one meetings between Professors Visweswariah and Frankel, it quickly became apparent that our interest in understanding the complexities of diarrheal disease was complementary. The focus of research in Professor Visweswariah’s laboratory is on the role of the cyclic nucleotides cAMP and cGMP in infection with the diarrhoeal pathogenic enterotoxigenic E. coli. (ETEC). Professor Frankel laboratory specialises in using murine models to study bacterial infections, with emphasis on in vivo imaging and the 3Rs principals. Importantly, due to the lack of a robust animal model, our understanding of the long term impact of ETEC infection on the gut physiology and the microbiota is incomplete.
The advantage of applying to the Royal Society International Collaboration Awards scheme to fund our ETEC project was that there was no need for extensive preliminary data and it would allow the exchange of personnel between the two laboratories, providing students and post-doctoral fellows the chance to experience research in two culturally diverse settings.
How does your research address a challenge affecting developing countries?
Diarrhoeal disease is a major cause of illness around the world, but the worst affected are children in developing countries. In endemic Low and Middle Income Countries in Africa and Southeast Asia, strains of ETEC that produce the enterotoxin ST and LT cause 280-400 million cases of diarrhoea in children under 5 years of age and over 300,000 deaths.
Frequent episodes of diarrhoea lead to stunted growth and the associated delay in developmental milestones can have an impact even later in life. Our research aims to understand why these frequent episodes of diarrhoea cause such severe illness. Are there permanent changes in gut physiology as a result of fluid and salt loss during diarrhoeal episodes? Are there changes in the gut microbiome that now result in sensitivity to certain dietary factors? Do these changes in the microbiome increase the susceptibility to other infections? We will use mouse models that mimic the disease seen in humans, and study the changes in the gut using advanced molecular and cell biology approaches. We anticipate that our work will lead to a greater understanding of the changes that occur in the gut that may also be seen in individuals that suffer from irritable bowel syndrome, Crohn’s Disease, and colon cancer.
What are the strengths of your collaboration?
The strength or our collaboration lies in our complementary expertise and approaches, both intellectually and experimentally. We see engagement of young researchers working in our lab in a collaborative project between UK and India an important added benefit. Moreover, we hope our collaborative project will fuel further interactions amongst younger faculty between the two Institutes, such as joint supervision of PhD students. More generally, changes in the economic climate of the UK and the growth of India as scientific force, our collaboration would showcase what is possible when these two historically linked nations attack a problem primarily relevant to the needs of developing countries, but also to the UK.
What do you hope you will achieve with this award?
Our aim over the next five years is to establish a strong and intimate collaboration between our laboratories at CMBI and IISc. Our expertise in infection and cyclic nucleotide signalling will enable us to build a robust model to study ETEC infection and the role of the ST enterotoxin receptor, G-CC, in health and disease, in vivo. By the end of the five years we would have profiled the gut responses to ETEC infection and activation of G-CC and its impact on the physiology of intestinal epithelial cells and the microbiota.