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MRC DiMeN Doctoral Training Partnership: Synthetic Teixobactins: Tackling Drug-Resistant Pneumonia Caused by S. pneumoniae and S. aureus

Funding
Funded
Study mode
Full-time
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Subject area
Biological and Biomedical Sciences
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Overview

Pneumonia remains one of the world’s most lethal infection syndromes. In 2021, two bacteria—Streptococcus pneumoniae and Staphylococcus aureus—were responsible for over 900,000 deaths globally, accounting for almost half of all pneumonia-related mortality. These pathogens therefore represent a critical unmet global health need, requiring urgent innovation in antibiotic discovery.

About this opportunity

We have discovered synthetic teixobactins (STexs), a new class of antibiotics with potent activity against resistant Gram-positive bacteria such as Methicillin Resistant Staphylococcus aureus (MRSA), without detectable resistance.

The overarching goal of this proposal is to evaluate a suite of synthetic teixobactins as potential treatments for pneumonia caused by drug resistant S. pneumoniae and MRSA. Previous studies have shown efficacy of STexs in mouse models of S. aureus keratitis and soft tissue infections.

This PhD project offers exceptional interdisciplinary training at the University of Liverpool within the Institute of Systems, Molecular and Integrative Biology. The student will join Dr Ishwar Singh’s Antimicrobial Drug-Discovery Group, internationally recognised for pioneering synthetic teixobactins—a new class of resistance-avoiding antibiotics targeting lethal infections such as MRSA and Streptococcus pneumoniae.

The project will provide comprehensive, targeted interdisciplinary training in antibiotic design, synthesis, and evaluation. The PhD student will design and synthesise novel teixobactin analogues, followed by in vitro microbiological and in vivo efficacy studies. They will gain core practical skills in solid-phase peptide synthesis and medicinal chemistry, undertake scale-up peptide manufacturing training during an industrial placement at Bachem UK, and receive advanced training in infection biology and animal models through collaboration with the Singapore Eye Research Institute.

This studentship offers a rare opportunity to work at the medicinal chemistry–microbiology–translation interface, with hands-on research experience across academic, and industrial settings, preparing the student for diverse careers in antimicrobial discovery and development.

Broader Impact

Synthetic teixobactins could revolutionise treatment for sensitive and resistant pneumonia and reduce global deaths from AMR infections. The student will contribute directly to developing a new antibiotic platform while gaining visibility in the UK’s national AMR and translational-research networks.

Dr Singh’s work has been widely featured in the media:

  • Revolutionary Thinking – The Biomedical Scientist (IBMS, 2022)
  • Antibiotic could save millions of lives from superbugs – Sky News, 29 March 2022
  • New killing mechanism discovered in game-changing antibiotic – University of Liverpool News, 2020

In 2025, the team won the Royal Society of Chemistry Emerging Technologies Competition (Health Category) for their synthetic teixobactin platform:

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond.

Further information on the programme and instructions on how to apply, including a link to the application portal, can be found on our website https://www.dimen.org.uk/

Further reading

1. Development of Teixobactin Analogues Containing Hydrophobic, Non-Proteogenic Amino Acids Highly Potent Against Multidrug-Resistant Bacteria and Biofilms
European Journal of Medicinal Chemistry (2023) 261:115853
PubMed: https://pubmed.ncbi.nlm.nih.gov/37604090
Publisher (Elsevier): https://doi.org/10.1016/j.ejmech.2023.115853
2. Mode of Action of Teixobactins in Cellular Membranes
Nature Communications (2020) 11:2848
PubMed: https://pubmed.ncbi.nlm.nih.gov/32503964
Publisher (Nature): https://www.nature.com/articles/s41467-020-16600-2
3. Design and Syntheses of Highly Potent Teixobactin Analogues Against Staphylococcus aureus, MRSA, and VRE in vitro and in vivo
Journal of Medicinal Chemistry (2018) 61:2009–2017
PubMed: https://pubmed.ncbi.nlm.nih.gov/29363971
Publisher (ACS): https://doi.org/10.1021/acs.jmedchem.7b01634
4. HAP-FAST: A Feasibility Study Incorporating Qualitative, Mechanistic and Costing Sub-Studies Alongside a Randomised Pilot Trial Comparing Chest X-Ray to Low-Dose CT and Empirical Antibiotics to Antibiotics Guided by the BIOFIRE® FILM ARRAY® Pneumonia Plus Panel in Adults with Suspected Non-Ventilator-Associated Hospital-Acquired Pneumonia
BMJ Open (2024) 14:e088490
PubMed: https://pubmed.ncbi.nlm.nih.gov/38964799
Publisher (BMJ Open): https://bmjopen.bmj.com/content/14/7/e088490
5. Risk of Cardiovascular Events After Acute Exacerbations of Chronic Obstructive Pulmonary Disease in Patients Receiving Long-Term Low-Dose Azithromycin
American Journal of Respiratory and Critical Care Medicine (2024) 209:1394–1396
PubMed: https://pubmed.ncbi.nlm.nih.gov/38502239
Publisher (ATS Journals): https://www.atsjournals.org/doi/full/10.1164/rccm.202309-1699LE
6. Low-Dose Azithromycin Prophylaxis in Patients with Atrial Fibrillation and Chronic Obstructive Pulmonary Disease
Internal and Emergency Medicine (2024) doi:10.1007/s11739-024-03653-0
PubMed: https://pubmed.ncbi.nlm.nih.gov/38819711
Publisher (Springer): https://doi.org/10.1007/s11739-024-03653-0
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Who is this for?

Applicants for postgraduate research study at Liverpool are normally expected to hold a UK first degree with a First Class or Upper Second Class degree classification, or a Second Class degree plus a Master’s degree. Equivalent international qualifications are also accepted, and their equivalence will be evaluated on the basis of the information provided by the European Network of Information Centres (ENIC) formerly NARIC as well as internal guidance based on our experience of a qualification’s suitability as a preparation for our programmes.

For applicants whose first language is not English, an IELTS score of 6.5 with no band score lower than 5.5, or an equivalent University of Liverpool acceptable English language qualification. For further details and other acceptable English language qualifications please see here: http://www.liv.ac.uk/study/international/countries/english-language/

Applications from candidates with prior research or industrial experience in antimicrobial drug discovery, peptide chemistry, or microbiology are particularly encouraged.

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How to apply

  1. 1. Contact supervisors

    The supervisory team combines world-class expertise across medicinal chemistrymicrobiology, and clinical medicine:

    Dr Ishwar Singh – Reader in Antimicrobial Drug Discovery and Medicinal Chemistry (University of Liverpool)

    Dr Daniel Wootton – NIHR Advanced Fellow & Senior Clinical Lecturer in Respiratory Infections (University of Liverpool & Liverpool University Hospitals NHS Foundation Trust)

    • Clinician-scientist with expertise in respiratory pathogens, clinical translation, and infection trials
    • Staff Profile
  2. 2. Prepare your application documents

    All applications are made via the application form accessed on the DiMeN website at www.dimen.org.uk/ Please read the full application guidance on the website before submitting an application.

  3. 3. Apply

    Finally, register and apply online. You'll receive an email acknowledgment once you've submitted your application. We'll be in touch with further details about what happens next.

    You should only follow this step if you’ve successfully completed the DiMeN application process

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Funding your PhD

Studentships are fully funded by the MRC for 4yrs, including a minimum of 3 months working with an industry partner. Funding will cover tuition fees and an enhanced stipend (£23,280 for 2024/2025) and project costs. We have a very small number of funded studentships for exceptional international applicants. Please read additional guidance here: View Website

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Contact us

Have a question about this research opportunity or studying a PhD with us? Please get in touch with us, using the contact details below, and we’ll be happy to assist you.

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