PhD: Clathrin-Coated Vesicle Formation & Drug Delivery

A funded PhD at the University of Warwick investigating clathrin-coated vesicle formation and mechanisms for drug delivery, through the Midlands Integrative Biosciences Training Partnership. Supervised by Prof Corinne Smith and Prof Stephen Royle. Open to students worldwide. See more funded PhDs.

Prof Corinne Smith, Prof Stephen Royle

Funded PhD Project (Students Worldwide)

About the Project

Clathrin-mediated endocytosis is a fascinating mechanical phenomenon that drives the selective internalisation of molecules into cells. Nutrient uptake, synaptic vesicle recycling, signalling and development all rely on endocytic mechanisms and malfunctions lead to tumour formation, neurodegeneration and heart disease. Our aim is to understand how the protein network of clathrin and its adaptor proteins achieves clathrin-coated vesicle formation and investigate ways in which this can be exploited for drug delivery.

There are two potential directions for this project. In the first, biophysical and structural biology techniques will be used to visualise adaptor proteins binding to clathrin cages and analyse the dynamics of those interactions. Using a combination of techniques such as high resolution cryo-electron microscopy, dynamic light scattering and time-resolved fluorescence anisotropy, the way in which clathrin-adaptor interactions result in formation of a functional coated vesicle network will be revealed.

In the second approach, the potential for lipid nanoparticles (LNPs) to be exploited as drug delivery agents within the endocytic pathway will be investigated. LNPs are key reagents in the delivery of therapeutic drugs and genes but present challenges such as large size, which limits cellular uptake, and vulnerability to manufacturing processes. We are developing an innovative alternative to traditional LNPs that addresses these challenges and exploits our understanding of endocytic mechanisms. In this project, alternative LNPs will be designed and characterised in terms of their biochemical and biophysical properties. Confocal microscopy, imaging flow cytometry will be used to track the location and effect of suitable candidate LNPs within cells. This will be followed by design and evaluation of chemical modifications to improve uptake and achieve delivery of reagents to specific cellular locations.