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Developing treatment for lysosomal storage diseases using 2D nanomaterials


   Faculty of Biology, Medicine and Health

  Dr Sandra Vranic,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Lysosomal storage diseases (LSDs) are metabolic disorders affecting 1 in 4000 live births with particularly severe impact on life quality and survival of infants and young adults. Standard therapy is administration of the missing enzyme so that the body can function properly. However, there are serious drawbacks, as administered enzyme does not reach all affected parts of the body. The aim of this project is to use two-dimensional, graphene-based nanomaterials with large surface area enabling attachment of higher amounts of enzyme to be delivered to the cells in the body. This material has exceptional biocompatibility and readily enters the cells thus carrying the enzyme to the location where it needs to exert its therapeutic effect. So far, 2D nanomaterials have not been used for this purpose even though there is a clear advantage mentioned above. We expect this project to pave the way to more effective therapies for LSDs.

This project is of multidisciplinary nature as it brings together expertise in 2D NMs synthesis and characterization, biological work focusing on therapeutic applications of NMs, study of nano-bio interactions as well as strong clinical support from leading experts in the field of rare metabolic disorders.

1.     Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject. Candidates with an interest in biological sciences (cell biology, molecular biology) / pharmacy / medical sciences / biomedical materials / chemistry / bio/chemical engineering are encouraged to apply.

2.     For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the PhD title.

3.     For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit www.internationalphd.manchester.ac.uk


Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website View Website
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website View Website

References

Relevant publications:
1. Vranic, S., Rodrigues, A., Buggio, M., Newman, L., White, M., Spiller, D., Bussy, C. and Kostarelos, K., 2017. Live Imaging of Label-Free Graphene Oxide Reveals Critical Factors Causing Oxidative-Stress-Mediated Cellular Responses. ACS Nano, 12(2), pp.1373-1389.
2. Chen, Y., Rivers-Auty J., Crica, L. E., Rosano, V., Arranz, A. E., Loret T., Spiller, D., Bussy C., Kostarelos, K., Vranic, S., 2021. Dynamic interactions and intracellular fate of label-free GO within mammalian cells: role of lateral sheet size. Nanoscale Adv., 2021,3, 4166-4185.
3. Mazza, M., Ahmad, H., Hadjidemetriou, M., Agliardi, G., Pathmanaban, O., King, A., Bigger, B., Vranic, S. and Kostarelos, K., 2019. Hampering brain tumor proliferation and migration using peptide nanofiber:siPLK1/MMP2 complexes. Nanomedicine, 14(24), pp.3127-3142.
4. de Lázaro, I., Vranic, S., Marson, D., Rodrigues, A., Buggio, M., Esteban-Arranz, A., Mazza, M., Posocco, P. and Kostarelos, K., 2019. Graphene oxide as a 2D platform for complexation and intracellular delivery of siRNA. Nanoscale, 11(29), pp.13863-13877.
5. McManus, D., Vranic, S., Withers, F., Sanchez-Romaguera, V., Macucci, M., Yang, H., Sorrentino, R., Parvez, K., Son, S., Iannaccone, G., Kostarelos, K., Fiori, G. and Casiraghi, C., 2017. Waterbased and biocompatible 2D crystal inks for all-inkjet-printed heterostructures. Nature Nanotechnology, 12(4), pp.343-350.
6. Shin, Y.*, Vranic, S.*, Just-Baringo, X.*, Gali, S., Kisby, T., Chen, Y., Gkoutzidou, A., Prestat, E., Beljonne, D., Larrosa, I., Kostarelos, K. and Casiraghi, C., 2020. Stable, concentrated, biocompatible, and defect-free graphene dispersions with positive charge. Nanoscale, 12(23), pp.12383-12394. *equal contribution.

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