Novel immunomodulatory therapeutic strategies to target intracellular pathogens

This is an exciting opportunity to work in the area of therapeutics and drug discovery at LSTM. You will be integrated into an extremely active research group with a diverse research portfolio. Projects will work towards the identification of novel therapeutic strategies targeting key intracellular pathogens (Mycobacterium tuberculosis, Nisseria gonorrhoeae, Salmonella enterica). Projects will utilise ex vivo human models of infection, advanced analytical techniques (confocal microscopy and flow cytometry), and pharmacodynamic-pharmacokinetic (PK-PD) modelling to study pathogenesis, resistance emergence, and to assess the clinical tractability of novel therapeutics. Projects will be tailored to the candidate and provide opportunity for industry training and overseas placement.

Where does the project lie on the Translational Pathway?

T1 – Basic Research

Expected Outputs

Publications as well as proof-of-concept data to support grant applications for further research towards changing clinical practice.

Training Opportunities

Training in the development of models of infection for the discovery and development of therapeutic strategies.

Practical training in use of the following analytical platforms:

1. Flow cytometry
2. High-content confocal imaging
3. Microfluidics
4. qPCR

Training in the following quantitative methods:

1. Statistical analyses
2. Bioinformatics

PK-PD modelling.

Skills Required

Background in biology/pharmacology and/or immunology. Interest in tackling real-life clinical knowledge-gaps and health issues.

Key Publications associated with this project

Donnellan S, Aljayyoussi G, Moyo E, Ardrey A, Martinez-Rodriguez C, Ward SA, Biagini GA. Intracellular Pharmacodynamic Modeling Is Predictive of the Clinical Activity of Fluoroquinolones against Tuberculosis. Antimicrob Agents Chemother. 2019 Dec 20;64(1):e00989-19. doi: 10.1128/AAC.00989-19. PMID: 31611354; PMCID: PMC7187570.

Jin C, Gibani MM, Pennington SH, Liu X, Ardrey A, Aljayyoussi G, Moore M, Angus B, Parry CM, Biagini GA, Feasey NA, Pollard AJ. Treatment responses to Azithromycin and Ciprofloxacin in uncomplicated Salmonella Typhi infection: A comparison of Clinical and Microbiological Data from a Controlled Human Infection Model. PLoS Negl Trop Dis. 2019 Dec 26;13(12):e0007955. doi: 10.1371/journal.pntd.0007955. PMID: 31877141; PMCID: PMC6948818.

Pennington SH, Ferreira DM, Caamaño-Gutiérrez E, Reiné J, Hewitt C, Hyder-Wright AD, Gordon SB, Gordon MA. Nonspecific effects of oral vaccination with live-attenuated Salmonella Typhi strain Ty21a. Sci Adv. 2019 Feb 27;5(2):eaau6849. doi: 10.1126/sciadv.aau6849. PMID: 30820452; PMCID: PMC6392763.

LSTM Themes and Topics – Key Words

‘Lung Health and Tuberculosis’, ‘Resistance Research and Management’