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Native state imaging and characterisation of hydrogels using advanced electron microscopy through the development of new techniques

   School of Pharmacy

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  Dr Christopher Parmenter, Dr Lisa White  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project


There is a long history of imaging soft matter, particularly of a biological nature, using cryogenic electron microscopy. For samples to be analysed using transmission electron microscopy (TEM) the dimensions are limited to a thickness of approx. 200 nm. Where samples cannot be directly deposited or grown on the grid, a sample preparation issue can be a stumbling block that requires advanced preparation. This is particularly true where the sample is a bulk sample, requiring cryogenic preparation, which must be maintained throughout the preparation procedures, including transfer into the TEM. As yet, there is no reliable solution for this, and it is a bar to the routine preparation of TEM suitable samples. The extracellular matrix (ECM) in native mammalian tissues provides a structural and functional framework to support tissue resident cells and promote cellular function. ECM derived hydrogels have considerable utility as vehicles for cell delivery in regenerative medicine and as 3D substrates for in vitro cell culture, but the full potential has yet to be reached. To date, characterisation of ECM hydrogel structure has been limited to freeze-drying, removing water from the hydrogels, which is not representative of the native state. There is a need for new imaging modalities to inform both understanding of the ultrastructure of ECM hydrogels and interactions of cells seeded within these materials.


We have an exciting opportunity for a PhD studentship involving the development of new imaging protocols and hardware for native state imaging of beam sensitive materials applied to regenerative medicine materials. The EPSRC iCase funded position will be a collaboration with an industrial sponsor to develop hardware and handling protocols in cryogenic microscopy. The aim will be to create a solution for routine FIB-SEM to TEM transfer to enable cryo-TEM of soft-matter samples.

This 4-year PhD project, based in the School of Pharmacy will utilize excellent cell culture facilities and state-of-the-art microscopy instrumentation available within the University’s nanoscale and microscale research centre (nmRC). Cryogenic Focused Ion Beam Scanning Electron Microscopy (Cryo-FIB-SEM) instrumentation will be employed to interrogate the nanoscale structures of gels and investigate the interactions of cells in the matrix as employed in a tissue culture setting.

This multi-disciplinary project combines practical skills in gel production, working in a cell culture setting and analytical science of gel materials. The project will combine these areas to better understand how the gel properties and cell types affect the cell-gel interaction within the 3D scaffolds for cell culture. The result will be an improved understanding of how these factors can be tuned for their desired application. This project seeks to make the most of the world leading capabilities and facilities available at the University of Nottingham particularly in biomaterials design and native state three-dimensional analysis.

The University of Nottingham has a long-standing reputation for world-class research and has a strong collegial ethos. The School of Pharmacy is ranked 5th in the world (2022 QS World Rankings) for pharmacy and pharmacology and was recently awarded an Athena Swan Silver award.

The successful candidate will:

-        Receive the training needed for a professional career as a multidisciplinary analytical scientist

-        Receive a full studentship tax free (fees and stipend at UK/EU rates) for 4 years

-        Work directly with leading academics and the industrial sponsor at their facilities for a period of 3 months

-        Receive a travel and consumable allowance

Funding Notes

The University of Nottingham has the capacity to augment a limited number of UKRI studentships to full international fees. This scholarship is eligible for this, but the award of international fees is subject to availability of these scholarship upgrades at the time of request. Due to these funding restrictions, the position may only be available for UK candidates. Funding is available for 4 years commencing October 2022.

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