Key information
Research topics
A 2026 Crick PhD project with Eachan Johnson.
Project background and description
As soon as new antimicrobial drugs are discovered and used in the clinic, pathogenic bacteria inevitably evolve resistance, driving an unsustainable cycle threatening the twentieth century's improvements to public health. Antibiotics revolutionized modern medicine, but previously curable infections once again threaten millions of lives. To tackle this emerging crisis, we need to discover inhibitors of new cellular targets faster than bacteria can evolve resistance, but conventional antimicrobial drug development too often either relies on minor modifications of known antibiotics to generate only marginally different “me-too drugs” or screening of large chemical libraries which yield repeated rediscovery of inhibitors of the same cellular targets.
This interdisciplinary PhD project aims to significantly advance approaches to antimicrobial discovery. It combines the Johnson lab’s expertise in chemical genomics, molecular genetics, and computation [1-3] to characterise the bioactivity of large, new swathes of chemical space, so that new collections of chemical inhibitors with novel cellular targets in pathogenic bacteria might be rapidly identified. Based on consultation with the candidate and their interests, this work could combine AI-guided drug discovery, computational curation of focussed chemical libraries, and biochemical and functional validation of small molecule mechanisms of action.
This project will provide opportunities to develop skills in biophysical techniques, bacterial genetics, microbiology, infection biology, high-throughput compound and genetic screening, chemical biology, quantitative biology, computational chemistry, and machine learning. There is also potential for collaboration with multiple groups at the Crick and other institutions.
Candidate background
We are looking for candidates with a background in quantitative biology, systems biology, or computational chemistry. The successful candidate will have at least some wet-lab experience, and an interest in infectious disease, microbiology, drug discovery, and molecular genetics. They will approach problems creatively, have excellent communication skills, be able to work collaboratively in a multidisciplinary research area, and will enthusiastically learn new techniques as required to achieve their research goals.
References
- Johnson, E.O., LaVerriere, E., Office, E., Stanley, M., Meyer, E., Kawate, T., . . . Hung, D.T. (2019) Large-scale chemical-genetics yields new M. tuberculosis inhibitor classes. Nature 571: 72-78. PubMed abstract
- Johnson, E.O., Office, E., Kawate, T., Orzechowski, M. and Hung, D.T. (2020) Large-scale chemical-genetic strategy enables the design of antimicrobial combination chemotherapy in Mycobacteria. ACS Infectious Diseases 6: 56-63. PubMed abstract
- Parkhill, S.L. and Johnson, E.O. (2024) Integrating bacterial molecular genetics with chemical biology for renewed antibacterial drug discovery. Biochemical Journal 481: 839-864. PubMed abstract
