Characterising the Cell Uptake, Intracellular Traffic and Transcytosis of Nanoparticles for Drug Delivery

We are inviting applications for three individual 3 year-PhD studentships in the combined fields of molecular cell biology, nanomedicines and drug delivery to commence from October 1 2013. The students will be physically based within the research environments of pharmaceutical sciences and biosciences at Cardiff University, part of the University’s College of Biomedical and Life Sciences. The projects are jointly supervised by Dr Arwyn Jones and Mark Gumbleton (Pharmacy) and Dr Pete Watson (Biosciences)

Across the host Schools there you will join a multidisciplinary group with a high reputation in cell biology, advanced microscopy techniques, biological barriers, nano-biotechnology and drug delivery research (1-4). Your personal effectiveness will be developed in an interdisciplinary and translational environment in a partnership between the host schools, the College of Biomedical and Life Sciences and the University Graduate College. You will have access to a wide range of expertise and training, support technologies and resources.

Background to the projects
Our current inability to deliver biopharmaceuticals such as peptides, proteins and genes into cellular targets is a major impediment to obtaining effective therapies against a range of diseases. These PhD studentships will be integrated into the objectives of COMPACT, a €30 million European academic and industrial consortium whose aim is to identify and understand transport pathways across major biological barriers that can be utilised for delivery of nanomedicines (http://www.compact-research.org/).

The successful students will acquire a variety of specialist skills utilising a wide range of state-of-the-art techniques including molecular biology, nano-biotechnology, chemical biology, advanced microscopy techniques and culture of epithelial and endothelial cells as models for biological barriers. It will be necessary for the students to interact closely with academic and industrial collaborators across COMPACT. Through their supervisors and international COMPACT collaborators they will be able to initiate publications in peer review journals, submit abstracts to meetings and attend national and international conferences.


Project Descriptions

Project 1 Developing Reporter assays to measure endosomal escape of therapeutic macromolecules: We aim to develop cell based reporter assays for assessing the capacity of drug delivery vectors such as cell penetrating peptides to translocate across endolysosomal membranes. For this the student will gain experience in cell culture, peptide biochemistry, cloning, transfection of cells, confocal microscopy and flow cytometry.

Project 2 Analysing endosomal pathways as routes for cellular delivery of nanomedicines: We aim to further our capacity to study the involvement of specific endocytic pathways as gateways for the uptake of nanomedicines into cells and across cellular barriers. For this the student will gain experience in cell culture, qualitative and quantitative analysis of endocytosis (confocal microscopy, flow cytometry), siRNA targeting of endocytic proteins and pathways to characterise of the uptake routes, and endocytic pathways utilized by nanomedicines.

Project 3 Delivery of biopharmaceuticals across the blood brain barrier.
We aim to investigate the capacity of nanomaterials to actively cross the blood brain barrier (BBB) with the objective that this could be translated to delivering biopharmaceuticals into the brain. The student will design, manufacture and characterise polymer based nanoparticles and protein formulations for targeting the BBB and in developing assays demonstrating BBB transcytosis. Experience will be gained in using polarized cell cultures as models for the BBB, in polymer chemistry, labeling of macromolecules and their analysis during transcytosis.