(MRC DTP) Design and synthesis of new antivirulence drugs for treatment of tuberculosis
Dr L Tabernero
Dr Sam Butterworth
Prof D Procter
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
Tuberculosis (TB) remains a major health problem that affects billions of people worldwide and the emergence of severe anti microbial resistance (AMR) to current antibiotics is now the main challenge to eradicate the disease. New strategies to treat and control this deadly disease are urgently needed. Mycobacterium tuberculosis (Mtb), the causing agent of the disease, is able to challenge the normal immune response and avoid killing within host macrophages, thus establishing infection. Both strategies depend on the action of secreted virulence factors that block the host antimicrobial functions. Hence, an alternative approach to the use of classic antibiotics is to block the action of such virulence factors to clear the infection. Our pioneering work on one such virulence factor, MptpB, and subsequent development of potent inhibitors, demonstrated the efficacy of inhibiting this target to control infection in animal models (Vickers 2018 J. Med. Chem). We have also identified inhibitors of another virulence factor, SapM, that impair survival of Mtb inside macrophages (Fernandez-Soto 2019, Sci. Reps). We now want to develop these initial hits using a combination of computational and medicinal chemistry to increase potency and selectivity while retaining cell activity. This project offers an exciting novel approach to design new antivirulence drugs for pharmacological intervention of TB, with potential applications to other infectious diseases.
Prof. Tabernero: https://www.research.manchester.ac.uk/portal/en/researchers/lydia-tabernero(c641e2ca-cbe4-422c-ab76-99cd87dcec3a).html
Prof. Procter: https://www.proctergroupresearch.com
Dr. Butterworth: https://www.research.manchester.ac.uk/portal/en/researchers/sam-butterworth(9371bed9-b45f-4a38-acc1-f62be234a52d).html
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website www.manchester.ac.uk/mrcdtpstudentships
As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.