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Harnessing Natural Neuroactive Metabolites for Enhancing Drug Delivery Across Ocular and Neurological Barriers
Secondary Supervisor(s): Dr Raquel Gil-cazorla and Dr Raj Singh Badhan
University of Registration: Aston University
BBSRC Research Themes:
Project Outline
Poor penetration of therapeutics across the blood-brain barrier (BBB) and blood-retinal barrier (BRB) limits progress in treating neurodegenerative and ocular diseases. This project explores a class of under investigated, lipophilic fungal metabolites with dual properties: neuroactivity and strong barrier penetration. Preliminary pharmacokinetic studies show these molecules achieve brain concentrations far exceeding plasma levels and can improve retinal cell survival following optic nerve injury. These findings suggest novel use of such metabolites as permeation enhancers to co-deliver therapeutic agents into immune-privileged tissues.
The student will employ a multidisciplinary integrated approach spanning molecular cell biology, pharmacology, and computational data analysis. Work will include:
1. Screening selected fungal metabolites for cytotoxicity and permeability effects in in vitro BBB and BRB models.
2. Exploring mechanistic pathways via transcriptomics, proteomics, and computational network analysis
3. Assessing barrier modulation using transepithelial electrical resistance (TEER), fluorescent tracer transport, and tight junction protein analysis (e.g., ZO-1, claudin-5).
4. Evaluating co-delivery with model small- and large-molecule therapeutics nanotechnology.
The project will provide advanced training in:
- Experimental techniques: mammalian cell culture, permeability assays, imaging, TEER, and molecular biology.
- Quantitative/data-driven methods: pharmacokinetic modelling, omics data integration, and bioinformatics.
- Translational skills: IP awareness, drug formulation concepts, and interdisciplinary collaboration.
- Transferable skills: scientific writing, communication, project management, and public engagement.
Impact
The project has the potential to create a new drug delivery paradigm using natural metabolites as permeability enhancers, with direct translational relevance to pharmaceutical, biotechnology, and ophthalmology sectors.
