NPBactID - Differential binding of peptoid functionalized nanoparticles to bacteria for identifying specific strains
Lead Research Organisation:
University of Strathclyde
Department Name: Pure and Applied Chemistry
Abstract
A rising public health crisis is antimicrobial resistance (AMR). A key mitigation strategy is to prescribe only the most appropriate antibiotics to reduce the off-targeting that leads to resistance. However, current methods to identify the cause of infection are generally laboratory-based and slow. Convenient, synthetic strain-specific affinity probes (SAPs) could in principle enable rapid, point- of-care biosensors but these are lacking in particular for identifying different strains of bacteria. This project will investigate a novel approach for developing SAPs by exploiting recent results from the host group showing that varying the functionalization directions and densities of antimicrobial "peptoids" immobilized on material surfaces can generate large differences in the surface attachment of different bacteria. Combined with the expertise of the postdoctoral researcher in nanoparticle (NP) synthesis and surface functionalization, this project will develop peptoid functionalized NPs as a novel SAP platform that can generate unique signals when the particles bind to different bacterial strains. We envision that this principle of differential surface functionalization combined with NP encoding can be adapted to a range of biosensing approaches, and thus open a new horizon in bacterial identification to help combat AMR.
| Description | The chemical understanding and synthesis of the antimicrobial peptide mimics developed is being applied to additional projects. This includes a partnership engagement with a biomedical device company to develop antimicrobial materials for potential use in their products. The company is providing £12000 towards this project. |
| First Year Of Impact | 2024 |
| Sector | Healthcare |
| Impact Types | Economic |
| Description | A Sustainably Resourced Advanced Coacervate Material Platform for Rapid Detection of Bacteria |
| Amount | £79,989 (GBP) |
| Funding ID | 1256 Lau Turkey |
| Organisation | British Council |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2025 |
| End | 08/2026 |
| Description | Towards practical multifunctional biomaterials: development of anti-infective and pro- endothelialisation vascular graft coatings |
| Amount | £124,904 (GBP) |
| Funding ID | PHD-50691-2023 |
| Organisation | Medical Research Scotland |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2024 |
| End | 09/2028 |
| Description | End-Group Acrylation of Polymers |
| Organisation | University of Strathclyde |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | In this collaboration, our primary contribution is the end-group acrylation of PCL diol to create acrylated polymer precursors suitable for further functionalization and 3D printing applications. We focus on optimizing the acrylation process to achieve high yield and purity, ensuring the modified PCL diols are ready for photopolymerization. |
| Collaborator Contribution | In this collaboration, Prof. Will Shu and his team member, Ian Mackenzie, have contributed their expertise in photopolymerization and 3D printing techniques. They have utilized the acrylated PCL diols synthesized by us to develop 3D printed structures for biological studies, optimizing the printing process, and will be evaluating the printed constructs in relevant biological environments. |
| Impact | This collaboration has led to the successful synthesis of acrylated PCL diols, which were utilized as precursors for photopolymerization-based 3D printing. Prof. Will Shu and his team applied these acrylated PCL diols to develop 3D printed constructs, optimizing the photopolymerization and printing processes. The printed structures are now in the phase of being evaluated for their performance and biocompatibility in relevant biological environments, offering valuable insights into their potential biomedical applications. This partnership is multi-disciplinary, bringing together expertise in synthetic chemistry (acrylation of PCL diols), materials science and engineering (photopolymerization and 3D printing), and biomedical science (evaluation of the biological applications of the printed structures). |
| Start Year | 2024 |
| Description | NMR Structural Investigations of Antimicrobial Peptoids in Membrane Environments |
| Organisation | University of Strasbourg |
| Country | France |
| Sector | Academic/University |
| PI Contribution | We design and synthesize NMR-active peptoids for bacterial membrane investigations, providing isotopically labeled, high-purity structures. |
| Collaborator Contribution | Prof. Burkhard Bechinger's team at the University of Strasbourg will conduct structural and interaction analyses using solid-state NMR and CD spectroscopy. |
| Impact | This collaboration has resulted in the successful design, synthesis, and purification of NMR-active peptoids tailored for bacterial membrane investigations. High-purity, isotopically labeled peptoid samples were prepared and shipped to Prof. Burkhard Bechinger's team at the University of Strasbourg for further structural and interaction studies. Using solid-state NMR and CD spectroscopy, their team will analyze the membrane interactions of these peptoids, providing valuable insights into their structural behavior. This multi-disciplinary partnership combines expertise in synthetic chemistry, focusing on peptoid design and purification, with biophysical chemistry for advanced spectroscopic analysis of membrane interactions. |
| Start Year | 2024 |
| Description | Synthesis of Antimicrobial Peptoids for Antimicrobial and Cellular Profiling |
| Organisation | University of Strathclyde |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | In this collaboration, my primary contribution is the synthesis and purification of the peptoid sequences to ensure high purity and structural integrity, which are essential for subsequent biological evaluations. |
| Collaborator Contribution | Rebecca and Ruchika, have contributed by conducting the antimicrobial assays and cell studies to evaluate the biological activity of the synthesized peptoids. They are responsible for testing the antimicrobial efficacy of the peptoids and assessing their effects on cells, providing valuable data on their potential for use in antimicrobial applications and their cellular interactions. |
| Impact | I contributed by synthesizing and purifying the peptoids to ensure they were of high quality and ready for evaluation. Rebecca and Ruchika conducted antimicrobial assays to assess the efficacy of the peptoids against various bacterial strains and performed cell studies to evaluate their cytotoxicity and interactions with cells. These studies provided valuable data on the antimicrobial activity and biocompatibility of the peptoids, supporting their potential therapeutic applications. This partnership is multi-disciplinary, integrating expertise in synthetic chemistry, microbiology, and cell biology. |
| Start Year | 2024 |