Disciplinary Head: Sam Willcocks
The Biological and Pharmacological Sciences discipline covers a wide range of areas; at its core we work directly with microbes in laboratory conditions to learn more about the mechanisms of resistance, and above all design effective new antimicrobials to fight disease.
A strength of the LSHTM is that is has a truly global presence. As such we have links and access to drug resistant strains of microbes from clinics and communities around the world, collected by researchers and collaborators for further study. We work on both neglected tropical diseases and emerging pathogens, as well as food-borne pathogens and hospital acquired infections.
There are several major concerns that we deal with. How does resistance arise, how does it spread, and how do our practices influence these? We seek to find better methods of measuring, diagnosing and predicting AMR; to identify new targets for the next generation of antimicrobials; and we consider the benefits of a paradigm-shift away from antimicrobials, towards control of infection through the commensal microbiome (bacteriotherapy), through immunomodulation, and through the application of the One Health philosophy.
Existing pharmaceuticals have served us well for many years, but they are failing for a variety of reasons. Microbes have always faced competition from other microbes in their environment, and they are adept at protecting themselves from biochemical attack. Modern medicine simply feeds into this evolutionary arms-race. We exacerbate AMR through misuse of drugs: over-prescription, uncontrolled or inappropriate use, expired or counterfeit antibiotics – and these issues apply to the farming and veterinary industry as much as to human medicine. Coupled with this, our production of new antimicrobials is slowing down due to the huge cost of discovery using current methods. These multi-faceted causes of AMR require not only multi-disciplinary, but inter-disciplinary solutions; and that is the aim of the AMR Centre at LSHTM: to bring our individual efforts to bear in a unified, holistic approach.
As part of the AMR Centre, the Biological and Pharmacological Sciences division is able to contribute to every level of understanding. Using next generation sequencing and cutting edge molecular techniques, we can monitor resistance at the multi-genome level, and use the information to discover genetic determinants of resistance. Through mutagenesis and protein expression systems, we can learn more about the role of specific resistance mechanisms in unprecedented detail. Ultimately, we are able to rationally design and screen novel antimicrobials and measure directly whether they are effective, and ensure that they are safe. In antibiotic design we work on both the ‘kill or not to kill’ approaches including the traditional destruction of bacteria and the new approach of disarming bacteria to facilitate immune clearance, the latter less likely to develop resistance. We also work on improving our available tools in diagnosing AMR at the point of contact, to speed up and lower the cost of this process. Finally, we work to build on tried-and-tested methods proven to combat AMR: antiseptics and vaccination.
We are one piece of the puzzle; through additional engagement with policy making, public education, and collaboration with industry, the Biological and Pharmacological Sciences at the LSHTM is working to be part of the solution to AMR.