PhD Studentship - Understanding chemical permeability and metabolism in gram-negative organisms

Supervisor: Professor Andres Floto (arf27@cam.ac.uk ) Department of Medicine, Heart and Lung Research Institute.

Project Summary:

Gram negative bacteria are major plant, animal, and human pathogens. There is an urgent unmet need to find new antibiotics against these pathogens (although little progress has been made in the last 40 years. Phenotypic screening has failed to find new compounds with novel mode of action while rational (structure-guided) antibiotic discovery has proved impossible in most cases because of a failure to understand the permeability, retention, and metabolism of chemicals. We have recently completed a systematic analysis of chemical retention and xenometabolism in mycobacteria (funding by the Gates Foundation) demonstrating that we can predict compound entry, retention and metabolism using ML approaches, for new unseen compounds to guide antibiotic discovery. The proposal will (i) modify these methods to map out permissive chemical space in a gram-negative bacteria, (ii) leverage existing mutant libraries to define molecular mechanisms of influx, efflux, and metabolism, and (iii) use this information to employ in silico screening and generative AI methods to create new antibiotics for soluble essential and vulnerable targets. The studentship will be co-supervised by Professor David Spring (Department of Chemistry).

This studentship is 3 years in length, from October 2025, and includes fees and maintenance for students eligible for Home fees. This studentship is part of BBRSC-Cambridge Biosciences Doctoral Training Partnership.

Applicants should hold (or expect to obtain) the equivalent of a UK 2.1 or higher in an undergraduate honours or Masters degree in a relevant subject.

To be appointed applicants must meet our minimum entry criteria which can be found at: https://www.postgraduate.study.cam.ac.uk/courses/directory/cvmdpdmed

For eligibility for home fees please check: https://www.postgraduate.study.cam.ac.uk/finance/fees/what-my-fee-status .

All applications should be made online via the University's Applicant Portal for a PhD in PhD in Medicine. Please apply via the application portal here - https://www.postgraduate.study.cam.ac.uk/courses/directory/cvmdpdmed

Please quote reference RC45508 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.