DepartmentSchool of Pharmacy and Biomedical Sciences
October, February and April
Applications accepted all year round
The work on this project will include:
- Fabrication of siRNA-loaded LNPs with optimized physicochemical properties using DOE and microfluidics combined with physicochemical characterization techniques
- Evaluating the in-vitro transfection efficiency and gene silencing of the LNPs in different cancer cell lines in 2D and 3D cell culture models
- Evaluating the in-vitro toxicity of the LNPs in normal human cell lines.
- Studying the cellular entry and trafficking of the LNPs.
The pharmaceutical and biomedical research is shifting towards using biological drugs (peptides, proteins, nucleic acids) instead of small molecule drugs for treatment of a wide range of diseases including infectious diseases, metabolic disorders, neurodegenerative diseases, and most notably cancer. Despite great advances in the field, there is still so much room for research to fill in the gaps and optimize the current practices. This project is aimed at developing lipid nanoparticles (LNPs) with optimized physicochemical properties for delivery of small interfering RNA (siRNA) to the cancer cells. It is an interdisciplinary project combining pharmaceutical science, nanomedicine, molecular and cell biology. The project will be carried out under supervision of Dr Roja Hadianamrei who has considerable experience in development of siRNA-based therapeutics for cancer and metabolic disorders in academia and pharmaceutical industry and Dr Sassan Hafizi who is an expert in cancer cell biology. siRNA are synthetic noncoding RNA which are capable of silencing selected genes in order to down regulate the unwanted proteins. LNPs are the new generation of non-viral gene vectors which have gained increasing attention in the last few years due to their successful application in mRNA based COVID vaccines. Applications of siRNA encapsulated in LNPs for gene therapy is a new promising approach in treatment of metabolic diseases and cancer. The first FDA approved siRNA drug, Patisiran (ONPATTRO®), consisting of siRNA encapsulated in LNPs has entered the market in US and EU in 2019.
In this project, a new library of LNPs will be generated using microfluidics. The LNPs will be functionalized with biological recognition elements targeting the cancer cells. The effects of formulation and process parameters on the physicochemical properties of the LNPs will be studied using design of experiment (DOE) approach. The LNPs with optimized physicochemical properties will be then tested for their ability to selectively deliver siRNA to the cancer cells and induce gene silencing in 2D cell cultures and 3D multicellular tumor spheroids. The cellular entry pathways and subcellular localization of the LNPs will also be studied. Working on this project will provide you with knowledge and practical skills in DOE, preparation of LNPs using microfluidics, analytical techniques (such as DLS, GE, UV, fluorescence spectroscopy, HPLC), microscopy techniques (confocal microscopy, TEM, AFM), cell culture and cellular assays (transfection and gene silencing), and molecular biology (qPCR and western blot).
Fees and funding
Visit the research subject area page for fees and funding information for this project.
Funding availability: Self-funded PhD students only.
PhD full-time and part-time courses are eligible for the UK Government Doctoral Loan (UK and EU students only – eligibility criteria apply).
Some PhD projects may include additional fees – known as bench fees – for equipment and other consumables, and these will be added to your standard tuition fee. Speak to the supervisory team during your interview about any additional fees you may have to pay. Please note, bench fees are not eligible for discounts and are non-refundable.
You'll need a good first degree from an internationally recognized university (minimum upper second class or equivalent, depending on your chosen course) or a Master’s degree in Pharmacy, Pharmaceutical science, Chemical Engineering, Materials Science or a related area. In exceptional cases, we may consider equivalent professional experience and/or Qualifications. English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.
- Relevant practical research experience in at least one of the following areas: Drug/gene delivery, Nanoparticle technology, Cell and molecular biology, Analytical chemistry.
- Familiarity with some of the techniques mentioned in the project description is an advantage.
- Prior experience working with lipid nanoparticles, siRNA or cancer cells is an advantage.
How to apply
When you are ready to apply, please follow the 'Apply now' link on the Pharmacy, Pharmacology and Biomedical Sciences PhD subject area page and select the link for the relevant intake. Make sure you submit a personal statement, proof of your degrees and grades, details of two referees, proof of your English language proficiency and an up-to-date CV. Our ‘How to Apply’ page offers further guidance on the PhD application process.
When applying please quote project code:PHBM5261024