Nanotherapeutics inspired by ‘Ehrlichs Magic Bullet’, aim to target disease (in humans, animals and plants), but still often lack specificity and there remain many questions to solve. We propose that rather than targeting the nanocarrier to the disease, we should modify the diseased tissue such that it ‘grabs’ the nanocarrier. If the modification results in a covalent (irreversible) bond, off-target effects (toxicity) can be removed and low concentrations should be able to achieve large effects.
In this project, we will explore how glycan (sugar) metabolism can be ‘hijacked’ to enable us to engineer the surface of diseased cells specifically. By hijacking how the glycans are processed, we can introduce new functionality onto the cell surface, while achieving selectivity for the diseased tissue. With this knowledge of glycan processing machinery we will target the tissue with therapeutics to give increased efficacy.
This exciting project will combine multidisciplinary aspects from biochemistry to polymer science, with potential for real impact. The GibsonGroup has previously developed nano/polymer systems for advance therapeutics (including antimicrobials) and also shown the proof of principle that we can recruit nanoparticles/polymers to cells.
- Covalent Cell Surface recruitment of Chemotherapeutic Polymers Enhances Selectivity and Activity, Chemical Science, 2021, 12, 4557-4569,
- Optimization and Stability of Cell–Polymer Hybrids Obtained by “Clicking” Synthetic Polymers to Metabolically Labelled Cell Surface Glycans; Biomacromolecules 2019, 20, 7, 2726-2736
- Re-engineering Cellular Interfaces with Synthetic Macromolecules using Metabolic Glycan Labelling, ACS MacroLetters, 2020, 9, 991-1003,
This project will enable a student to be exposed to a unique biomaterials environment and learn/apply multidisciplinary skills in synthetic biomaterials but also cell biology and advanced analytics, using confocal microscopy and flow cytometry. (https://warwick.ac.uk/fac/sci/chemistry/research/gibson/gibsongroup/). It also benefits from collaboration with Dr Arno, an expert in Biomaterials at the University of Birmingham. Her research focusses on the development of functional, biocompatible polymeric materials that can control cell behaviour, including cell proliferation, migration, adhesion, and differentiation.
- Engineering the Mammalian Cell Surface with Synthetic Polymers: Strategies and Applications, Rapid Commun. 2020, 41, 2000302.
- Exploiting the role of nanoparticle shape in enhancing hydrogel adhesive and mechanical properties, Nat. Commun. 2020, 11, 1420.
Key objectives will include:
- Probing glycan uptake and metabolism to hijack the cell surface
- Cell specific targeting by glycans to be monitored by fluorescent probes
- Cell-specific (or selective) chemical labelling using nanoparticles
- Demonstrate function in a 3-D spheroid tumour model
Current diagnostics are often based on either growing the infectious agent (e.g plating out a swab) or rely on genetic techniques such as PCR (polymerase chain reaction). A key challenge is that these need infrastructure and trained personnel. Also results are not ‘instant’ and the assays are expensive. We have recently disclosed a method to identify SARS-COV-2 (cause of COVID) using a paper-based device which gives an answer in under 30 minutes.
ACS Central Science, 2020, The SARS-COV-2 spike protein binds sialic acids, and enables rapid detection in a lateral flow point of care diagnostic device. Online.
Crucial to this technology was the understanding of how glycans (sugars) act as ‘anchors’ for virus, bacteria and their toxins to ‘grab’ hold of their hosts at the initial stages of infection. We aim to understand how pathogens bind these sugars, and then to reproduce these structures on the surface of nanomaterials to generate sensors. These have broad applicability across animal health (both domestic and agricultural), bioterrorism (e.g ricin detection), sanitation (cholera detection) and more.
This is a huge field, and a student would have the chance to work with us on dissecting how pathogens interact with glycans. There are several targets which we available to work on, which would be agreed with the student.
This project will enable a student to be exposed to a unique biomaterials environment and learn/apply skills in synthetic biomaterials but also cell biology and advanced analytics, using confocal microscopy and flow cytometry. The GibsonGroup (https://warwick.ac.uk/fac/sci/chemistry/research/gibson/gibsongroup/) has unique facilities enabling such an ambitious cross-disciplinary project, and the student will learn nano science as well as microbiology and analytical skills.
Key objectives will include;
- Dissection of pathogen/glycan interactions
- Recapitulate glycans onto nanomaterial surfaces
- Demonstrate sensing in a physiologically relevant medium
BBSRC Strategic Research Priority: Understanding the rules of life – Systems Biology, Immunology, and Stem Cells, and Integrated Understanding of Health - Pharmaceuticals, Regenerative Biology, and Ageing.
Techniques that will be undertaken during the project:
Carbohydrate Chemistry
Polymer Chemistry
2D and 3D Cell culture
Confocal microscopy
Flow Cytometry
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