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Platform Technology to Enhance the Growth of Human Tissues In Vitro for Use in Biomedical Research and the Assessment of New Molecular Entities


Department of Chemistry

About the Project

Many molecules fail when tested in humans as activity data do not always extrapolate into man. Accordingly, there is demand to develop new biomedical in-vitro assays to test compounds in human tissues earlier in product development. This interdisciplinary technology-based project aims to develop a novel in vitro system that is designed to maintain human tissue models over extended periods to enable the chronic testing of new compounds. We will design and engineer a unique bench-top bioreactor dedicated to supporting viable bioengineered tissue equivalents and ex-vivo tissue samples and evaluate the testing on novel senolytic molecules under development in our laboratory.

Research Project


Background:
Testing the activity of molecules prior to human use is an essential step in the development of new drugs. Currently it is very challenging to evaluate compound activity and toxicity in human tissues directly due to the lack of appropriate test systems. In-vitro biomedical tests on human cells are possible using conventional two-dimensional (2D) cell culture techniques however the assays do not represent the true activity of molecules in real tissues. Three-dimensional (3D) cell culture radically improves cell structure and function enabling the formation of tissue-like constructs. At Durham University, we developed Alvetex technology, which is now the market leading scaffold-based product for 3D cell culture.

Objectives:


This project involves the design and engineering of a new and innovative approach to combining 3D cell culture technology and the development of a novel bioreactor to maintain human tissues for in-vitro biomedical assays. This is an interdisciplinary project drawing on expertise in biomedicine, chemistry and engineering (Przyborski (Durham); von Glinicki (Newcastle); Williams (Durham); Bunton (Reprocell)).

The mode of perfusion within the bioreactor will be informed by data from fluid dynamic simulations to control media flow and shear stresses across the cell/tissue models. Cells and tissues will be supported by porous membrane materials fabricated from polystyrene to enhance molecular exchange between cells and medium. The bioreactor will incorporate oxygen control mechanisms through a combination of oxygen monitoring probe and gaseous exchange.

We hypothesise that our design will extend the viability of cell and tissue models for chronic exposure studies and the testing new compounds over time. For the purposes of this project, we will demonstrate its application to the long-term maintenance of human skin models of ageing and human aged skin ex-vivo. In collaboration with an existing UKRI-funded project, we will examine the chronic effect of new senolytic molecules on human skin models maintained in the bioreactor as a strategy to enhance skin quality during ageing.

Training & Skills


The student will become part of a productive research laboratory in Durham and will receive guidance and technical training working directly alongside experienced staff and will meet fortnightly with the supervisor to review progress. They will also benefit from collaborators in other disciplines contributing to the project. The student will interface with the industrial partner, working at their site, acquiring tissue samples, and interacting with end-users to help instruct and optimise design. They will also visit and work with our academic and industry partners in Newcastle and Glasgow, introducing new senolytic interventions to test and evaluate on human skin tissues using the new technology.

Specific training/skills include:
- advanced cell culture technologies
- maintenance of human cells/tissues
- bioengineering human skin
- cell and molecular biological analyses
- microscopy and advanced imaging
- design and prototyping of novel devices
- fluid dynamic analysis of perfusion
- develop new drug treatment regimes
- test chronic exposure of skin treatments
- produce publications and reports

Entry Requirements


Applicants should hold or be expected to get an excellent Masters level degree in a relevant subject. A first class Bachelor’s degree with relevant experience will also be considered.


Further Information


Informal enquiries regarding this project can be made to Professor Stefan Przyborski:


How to Apply


To apply for this project please visit the Durham University application portal to be found at: https://www.dur.ac.uk/study/pg/apply/

Please select the course code F1A201 for a PhD in Molecular Sciences for Medicine and indicate the reference MoSMed20-14 in the ‘Field of Study’ section of the application form.

Should you have any queries regarding the application process at Durham University please contact the Durham MoSMed CDT Manager, Emma Worden at:

The closing date for applications is Friday 24th July 2020.

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