Superselective targeting of perineuronal nets in the brain

Ever wondered how our neurons maintain synaptic connections stable over time? Perineuronal nets (PNNs) are one of the key reasons. PNNs surround the body of neurons as a mesh-like coat made of extracellular matrix molecules. Synapses reside in the holes of the mesh, and the mesh keeps the synapses in place. How exactly PNNs perform this important function remains rather poorly understood. Research in this area is hindered by the lack of probes to visualise PNNs in vitro and in vivo. The extracellular matrix molecules that make PNNs are also present in interstitial matrix, albeit at reduced density, making for poor contrast with conventional probes. An effective PNN probe must be able to sharply discriminate PNNs against interstitial matrix, by responding strongly to small differences in the local concentration of ECM molecules. The aim of this project is to develop such a ‘superselective’ probe.

This project will combine protein biochemistry and bio-orthogonal chemistry to make superselective probes, soft matter concepts and biophysical experiments to validate and tune the performance of the probes, and cell biology techniques to test and use the probes on perineuronal nets for the study of their functions in neuroscience.

The project is offered by a cross-disciplinary team of supervisors. Successful applicants will bring some of the expertise required for this project, and a strong interest in interdisciplinary work. Training on additional techniques will be provided as part of the project by the supervisors and their collaborating research teams.

To find out more about our research programs, see the websites and X (formerly known as Twitter) profiles of the research lab participating in this project:

Websites

– Richter Lab – richterlab.org

– Kwok Lab –

https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/99/dr-jessica-c-f-kwok

– Turnbull – https://eps.leeds.ac.uk/chemistry/staff/4194/professor-bruce-turnbull

X (previously known as Twitter)

@LabRichter

@KwokLab

@wbturnbull