2025-26 Project (Hilpert & Osborn & Nothurfft)

Activity and toxicity of AI-Driven Antimicrobial Peptides Against WHO Priority Pathogens

SUPERVISORY TEAM

Supervisor

Dr Kai Hilpert at City St George’s
Email: khilpert@sgul.ac.uk

Co-Supervisor

Dr Daniel Osborn at City St George’s
Email: dosborn@sgul.ac.uk

Co-Supervisor

Dr Axel Nothurfft at City St George’s
Email: anohturf@sgul.ac.uk

PROJECT SUMMARY

Project Summary

Are you passionate about tackling one of the world’s greatest health challenges-antibiotic resistance? Join our dynamic research team and contribute to cutting-edge work in discovering next-generation antimicrobial peptides (AMPs) using advanced AI tools. Our project focuses on identifying and synthesizing novel AMPs from vast genomic datasets to combat multi-drug-resistant bacteria. You will gain hands-on experience with AI-driven predictions, peptide synthesis, microbiological screening, and toxicity testing using cell lines and zebrafish embryos. This PhD project offers a unique opportunity to work in a leading lab with over 25 years of experience in antimicrobial peptide research. If you’re excited about innovation and making a real-world impact, this is the perfect position for you!

Project Key Words

Antimicrobial resistance, artificial intelligence,  zebrafish, peptides

MRC LID Themes

  1. Infectious Disease
  2. Translational and Implementation Research
  3. Global Health

Skills

MRC Core Skills

  1. Interdisciplinary skills
  2. Whole organism physiology
  3. Quantitative skills

Skills we expect a student to develop/acquire whilst pursuing this project

Basic microbiological skills to grow and test bacteria. Ability to synthesize and analyse peptides. Screening peptides for antimicrobial and cytotoxic activity. Ability to use AI-based tools to predict and rank antimicrobial peptides. Mode of action studies.

Routes

Which route/s are available with this project?

  • 1+4 = Yes
  • +4 = Yes

Possible Master’s programme options identified by supervisory team for 1+4 applicants:

  • City St George’s – MRes Biomedical Science – Infection and Immunity

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? Yes

Location & Travel

Students funded through MRC LID are expected to work on site at their primary institution, meeting – at the minimum – the institutional research degree regulations and expectations. Students may also be required to travel for conferences (up to 3 over the duration of the studentship), and for any required training (for research degree study). Other travel expectations and opportunities highlighted by the supervisory team are noted below.

Primary location for duration of this research degree: City St George’s, London

Travel requirements for this project: Travels to conferences to present poster/talk

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

  • Minimum City St George’s institutional eligibility criteria for doctoral study.

Other useful information

  • Potential Industrial CASE (iCASE) conversion? = No

PROJECT IN MORE DETAIL

Scientific description of this research project

Context and Significance:
Antibiotic resistance is recognized by the World Health Organization (WHO) as one of the most critical threats to global health and food security. The rise of resistant infections leads to longer hospital stays, increased medical costs, and a higher mortality rate. In 2019 alone, antibiotic resistance contributed to 1.2 million deaths worldwide. If left unchecked, we may soon face a reality where common infections and minor injuries become life-threatening, and even routine surgeries carry significant risks. This scenario would undermine the foundation of modern medicine.

One promising solution is the development of antimicrobial peptides (AMPs). These naturally occurring molecules are effective against multi-drug-resistant (MDR) bacteria and exhibit diverse mechanisms of action, making them less susceptible to existing bacterial resistance pathways. This diversity opens the door to developing new, urgently needed drugs.

The Opportunity
Antimicrobial peptides (AMPs) as a resource: AMPs are a valuable and underutilized resource. Their natural diversity and broad activity against MDR bacteria and fungi make them strong candidates for drug development. Our team has the unique capability to synthesize thousands of AMPs and rigorously screen them for antimicrobial efficacy and toxicity, positioning us to lead in this vital area of research.   

Genomic discovery of novel AMPs: The rapidly growing repository of sequenced genomes-now including over 18,000 fully sequenced organisms and 15,000 partial genomes-presents a tremendous opportunity for novel AMP discovery. With sequencing costs continually dropping, this data pool expands daily. Cutting-edge AI tools are now available to mine these genomes and predict new AMPs, offering a powerful and efficient approach to uncovering next-generation antimicrobial agents.

Early toxicity screening: The recent failure of an AMP in phase III clinical trials underscores the importance of early toxicity testing and a deeper understanding of AMPs’ mechanisms of action. To avoid similar setbacks, we will focus not only on the antimicrobial activity of AI-predicted AMPs but also on their toxicity profile. This will involve testing on various cell lines and in zebrafish embryos, ensuring a comprehensive evaluation of both efficacy and safety.

Techniques to be Used
Our approach integrates a range of advanced techniques to maximize the discovery and development of promising AMPs.
AI-driven prediction: We will utilize state-of-the-art AI tools to predict the most potent peptides from large genomic datasets.
Peptide synthesis: Using cellulose-based peptide synthesis, we can efficiently produce large libraries of peptides for testing.
Microbiological screening: Standard microbiological methods will be employed to grow bacteria, and our established high-throughput screening protocol will be used to assess the antimicrobial and cytotoxic activity of the synthesized peptides.

Mechanism of action studies: For the most active peptides, we will conduct detailed investigations into their mode of action, gaining insights that can inform further development.

Our laboratory has 25 years of experience specializing in antimicrobial peptides, with a proven track record of success. Preliminary studies using AI tools have already yielded promising results, demonstrating a high likelihood of success in this project. We have also established all the toxicity screening assays.

Further reading

Relevant preprints and/or open access articles:
(DOI = Digital Object Identifier)

Additional information from the supervisory team

The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.

Hilpert-Osborn-Nothurfft recording

MRC LID LINKS

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