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Closing date: 20th January
A competition-funded PhD with Dr Nik Hodges at the School of Biosciences, University of Birmingham, developing SMA polymer nanoparticles to carry poorly soluble drugs and probes into cells, with applications including getting compounds across the blood-brain barrier to treat conditions like Alzheimer’s and ALS. Open to UK and European students. See more funded PhDs.
University of Birmingham, School of Biosciences
Supervisor: Dr N J Hodges
Competition Funded PhD Project (European/UK Students Only)
About the Project
SMA) polymers and SMA lipid particles (SMALPs) have previously developed in the Dafforn lab to isolate and characterise membrane proteins. The aim of this project is to develop these materials as novel nanomaterials for the encapsulation and mobilisation of highly lipophilic small molecules to enhance their cellular uptake and biological activity.
Rational
Low water solubility and limited cellular availability of otherwise useful molecules can hinder their biological utility. For example, as molecular imaging probes in vitro or as bioactive molecules (including pharmaceuticals. In vivo and in vitro). Therefore, new approaches to increase cellular uptake would be beneficial to many areas of life sciences including medicine. Potential example applications include improving bioavailability/activity in vivo (e.g., retinoic acid), enhancing blood brain barrier penetration, to target compounds to the CNS to treat neurodegenerative conditions like Alzheimer’s and ALS (e.g., ropinirole), reducing toxicity of anti-cancer agents (e.g., doxorubicin) by improving cellular targeting and reducing systemic exposure. Previous work in our lab as proof of concept has already demonstrated that SMA nanoparticles can be used to encapsulate retinoic acid, making it four to five orders of magnitude more water soluble whilst remaining in a form that is biologically active in cells (e.g., induction of CD38 in HL60 cells). This project will explore and develop further the use SMA and SMALPs to encapsulate biologically active molecules and study their delivery and biological activity in cellular systems. If successful, the most interesting complexes will be assessed further using animal disease models to study cellular uptake and activity in vivo.
Methods
- Synthesis and characterisation of nanoparticles (gel filtration, DLS, electron microscopy, mass spectrometry)
- Study of cellular uptake (cell culture, flow cytometry, confocal microscopy,)
- Assessment of biological activity and toxicity (western blotting, PCR, ELISA, MTT assay)
For informal enquiries about this opportunity please contact Dr Nik Hodges (n.hodges@bham.ac.uk) directly
Funding notes:
Funding is available please contact directly for more information
References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675821/
https://pubmed.ncbi.nlm.nih.gov/15196749/
https://www.sciencedirect.com/science/article/pii/S1773224713500359
To apply for this job please visit www.findaphd.com.
