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New anti-virulence bioresponsive nanoparticles to treat pulmonary TB (GCRF)

Project Description

Pulmonary tuberculosis is one of the leading causes of death globally. The disease is particularly affecting significant proportions of population among the poorest countries. While United Nations has set targets to end TB, in almost a decade from now, there are major obstacles in the way to reach such a goal as drug resistant strains are on the rise and cure rate for patients infected with these strains remains low. This poses significant health security threat in countries like India where the TB burden is highest. Ending the tuberculosis epidemic by 2030 is among the health targets of the Sustainable Development Goals, however this can only be realised if more innovative approaches in developing new treatment options are urgently brought into play to tackle the epidemic head on.

Mycobacterium tuberculosis (Mtb) primarily infects alveolar macrophages (AMs) where it is able to live intracellularly for extended periods of time. Mtb creates its own safe environment, inside the infected macrophage, by secreting a number of virulence factors to inhibit the natural antibacterial mechanisms of the AMs. Most drugs have poor permeability to enter macrophages making treatments less effective at killing intracellular infections. Nanoparticles, particularly decorated with targeting ligands has the potential to generate new medicines since such particles can also be taken up into macrophages, just like pathogens. However to treat pulmonary infection the nanoparticles need to be made highly stable and of correct size for lung deposition in order to be delivered in inhalable form. There is tendency for stable nanoparticles to remain intact and not release the drug efficiently intracellularly. This project intends to solve all these limitations by designing and testing novel nanoparticle formulations which can be sensitised with targeting ligand, combined with bio-polymeric system and incorporate pH triggering mechanism to release the drug inside the alveolar macrophages. Furthermore the project will utilise new pioneering drugs against the Mtb secreted virulence factors discovered in our laboratories. These drugs have proven success in inhibiting the MptpB target which is therapeutically unexplored but shows efficacy in curtailing infection in animal models.

This project will utilise skills and knowledge base from Manchester University (School of Health sciences) and Delhi University (K.M college) to enable a new interdisciplinary approach for a breakthrough treatment based on designing novel controlled drug delivery system targeted to the to the vicinity of the mycobacterium at nanaoscale intracellular level.

The successful candidate will join a multidisciplinary research team and will be able to work in both UK and India and will also be supported by the principal investigators exchange of visits between the two countries through an already established collaboration links. Nanoparticle technology development and formulation will take place in the Division of Pharmacy and optometry (Dr Aojula), the efficacy testing will be performed Division of Infection, Immunity & Respiratory Medicine (Prof Tabernero) using well established alveolar macrophage infection model while biopolymeric incorporation of nanoparticles will be studied by shorter visits to K. M. College, University of Delhi (Dr Verma).

Entry Requirements
Candidates are expected to hold (or be about to obtain) an Upper Second class Honours degree (or equivalent) in a related area / subject.

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 - choose PhD Infectious Diseases. Full details on how to apply can be found on the GCRF website https://www.manchester.ac.uk/study/postgraduate-research/golden/gcrf/

Funding Notes

The GCRF PhD studentship programme is a 4 year programme with integrated teaching certificate. There are up to 12 studentships available. Applicants can apply to one project which will start in either April or September 2020.

Funding for the programme will include tuition fees, an annual stipend at the minimum Research Councils UK rate (around £15,000 for 2019/20), a research training grant, training allowance and travel allowance.

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.

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