Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2022 and will register for their PhD at one of the Crick partner universities (Imperial College London).
This 4-year joint Crick PhD studentship is offered in the Group labs of Dr Eachan Johnson and Dr Louise Walport, based at the Francis Crick Institute (the Crick).
The WHO recently declared that the increasing incidence of antibiotic drug resistance is fuelled by a lack of innovative anti-bacterial modes of action[1]. All clinical antibiotics target a handful of essential bacterial processes, but bacteria have acquired, over billions of years, the ability to evolve rapidly, enabling population level survival in the face of chemical insults. Next generation antibacterial treatments might instead interfere with bacterial evolvability or augment the host’s ability to control infection, but this approach requires detailed understanding of infection processes and how they could be chemically manipulated.
This interdisciplinary PhD project focuses on tuberculosis, which is a global top-10 cause of death and is caused by the intracellular pathogenic bacterium Mycobacterium tuberculosis. Tuberculosis treatment is increasingly frustrated by rising rates of multi-drug resistance, which can necessitate 24-month treatment regimens with only a 50% cure rate. By combining the Walport lab’s expertise in peptide chemistry and the Johnson lab’s focus on M. tuberculosis, this project aims to improve understanding of M. tuberculosis infection processes and how they might be modulated with highly target-specific peptides. Using peptides complements conventional approaches because they are highly target-specific and have a diverse repertoire of modes of action including disrupting challenging drug targets such as protein-protein interactions [2, 3].
In collaboration with the Crick’s Scientific Technology Platforms, the candidate will develop ultra-high throughput, miniaturised assays to gather quantitative phenotypes [4, 5] which characterise macrophage infection with M. tuberculosis. In parallel, they will generate very large libraries of genetically barcoded, cell-permeating cyclic peptides from the RaPID platform [2, 3]. The miniaturised assays and peptide libraries will then be applied to identifying new bioactive peptides and their quantitative phenotypes. Using technology from the Walport lab, they will simultaneously isolate the targets of these bioactive peptides, directly linking infection phenotypes to cellular targets and mechanisms.
The project will provide opportunities to develop skills in peptide synthesis, biophysical techniques, microbiology, infection biology, high-throughput screening, and chemical biology. There is also potential for collaboration with multiple groups at the Crick and other institutions.
Candidate background
We are looking for enthusiastic candidates with a background in chemistry or chemical biology and an interest in infectious diseases, microbiology, drug resistance, or technology development.
Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.
APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE (ACCESSIBLE VIA THE ‘INSTITUTION WEBSITE’ LINK ABOVE) BY 12:00 (NOON) 11 November 2021. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
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