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Uncovering the mechanisms of cryoprotectant toxicity and improving cryopreservation protocols


Project Description

Cryopreservation is the process of placing cells, organs or even whole organisms at low temperatures so that they remain in a state of suspended animation and function is preserved. Cryobiology is a crucial area of research for modern biotechnology due to the importance of biobanking, from developing reliable stem cell storage systems, organ banking for transplants as well as storage for engineered tissues. At present, cryopreservation technology is only successful for cell lines and very small tissues. More research is required before whole organs can successfully be cryopreserved while retaining their biological integrity. Given the importance of organ transplants and the growing field of tissue engineering, perfecting cryopreservation methods would have a profound impact on medicine.

We are looking for an enthusiastic and ambitious student to study cryopreservation and cryoprotectant toxicity. The constraints placed by delicate biological structures set many challenges for the science of cryopreservation. The chemicals which block ice formation and remove intracellular water (called cryoprotectants) are also toxic, to varying degrees. The complexity of this toxicity effect has been the biggest barrier to clinical application of vitrification in human tissues and organs. To unravel this complex sequence of interactions, we are using many techniques combined with genomic methods to study the mechanisms of cryoprotectant toxicity in human cells. Our goal is to identify genes and other mechanisms at work in cryoprotectant toxicity; this will give us direct targets for drug discovery. The exact direction of this project, however, will be adapted to fit the research interests of the student. Ultimately we aim to improve cryopreservation protocols to make long-term storage of stem cells, engineered tissues and organs more efficient.

Further details about our work on cryopreservation are available at:
http://cryopreservation.org.uk/

More information about our lab is also available online:
https://www.liverpool.ac.uk/ageing-and-chronic-disease/staff/joao-de-magalhaes/

Potential applicants are encouraged to contact Dr de Magalhaes () in the first instance for an informal discussion.

Funding Notes

This project is open to applicants who are able to obtain their own funding for tuition fee, consumable laboratory costs and living expenses.

A fees bursary may be available for suitably qualified applicants.

References

Cordeiro RM, Stirling S, Fahy GM, de Magalhães JP (2015) "Insights on cryoprotectant toxicity from gene expression profiling of endothelial cells exposed to ethylene glycol." Cryobiology 71:405-412.

Guibert et al. Organ preservation: current concepts and new strategies for the next decade. Transfus Med Hemother 38, 125–142 (2011).

Fahy et al. Cryopreservation of complex systems: the missing link in the regenerative medicine supply chain. Rejuvenation Res. 9, 279–291 (2006).

Fahy et al. Cryopreservation of organs by vitrification: perspectives and recent advances. Cryobiology 48, 157–178 (2004).

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