Engineering biology for neuroplasticity: protein-based nanocarriers for targeted delivery of nucleic acids to neurons

Perineuronal nets (PNNs) are extracellular structures that stabilise synapses and restrict neuroplasticity in the adult brain. Modulating PNNs can promote neuronal regeneration and functional recovery, but efficient delivery of macromolecular therapeutics like siRNA into PNN neurons remains a major challenge. This project will use engineering biology to reprogram the non-toxic B-subunit of cholera toxin (CTB), a neuronal tracer that binds GM1 gangliosides and undergoes retrograde transport, into a precision delivery platform for nucleic acids. You will design CTB-based carriers using cleavable peptide linkers and reversible complexes with engineered binding proteins (Adhirons), enabling controlled intracellular release. These systems will be applied to downregulate key PNN components to enhance plasticity. The project integrates protein engineering, chemical biology, and quantitative metrology, offering training in advanced conjugation chemistry, imaging, and functional assays. This PhD is ideal for students with a background in chemistry, biochemistry, or related disciplines.