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Details of Grant 

EPSRC Reference: EP/T017473/1
Title: Biomimetic Crystallisation of Metal-Organic Materials for Protein Isolation and Stabilization
Principal Investigator: Riddell, Dr I
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Chemistry
Organisation: University of Manchester, The
Scheme: New Investigator Award
Starts: 01 February 2020 Ends: 31 January 2022 Value (£): 149,340
EPSRC Research Topic Classifications:
Biophysics Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
24 Oct 2019 EPSRC Physical Sciences - October 2019 Announced
Summary on Grant Application Form
Proteins have evolved over hundreds of years to perform a wide variety of highly sophisticated tasks, however their structural fragility continues to limit their application beyond biological settings. Development of an encapsulation strategy capable of supporting the three-dimensional structure of proteins that often gives rise to their desirable properties, is therefore essential if the full potential to utilise proteins is to be realised. Specifically, benefits arising from protein stabilisation are foreseen in:

i) the manufacturing sector where enzymes may be able to replace expensive and environmentally toxic catalysts currently in use,

ii) in healthcare where purification and instability issues raise the cost of protein pharmaceuticals limiting their application for long-term disease management and their use in the Third World, and also

iii) in research science where biologists strive to understand how enzymes function within confined spaces.

This proposal will systematically evaluate the materials properties most suited for encapsulating and stabilising proteins in their native state. A biologically inspired crystallisation methodology is proposed where metal-organic frameworks (MOFs) assemble around proteins in solution, thus avoiding limitations associated with the synthesis and stability of MOFs with sufficiently large internal void pockets to accommodate proteins. A wide variety of conditions will be screened in the initial stages of the project to evaluate the metal, organic ligand, crystallisation conditions and protein properties best suited to biomimetic crystallisation of MOFs without negatively impacting the protein. Encapsulation of purified proteins as well as those introduced in complex biological mixtures will be evaluated.

Following optimisation of the crystallisation conditions a range of enzymes will be encapsulated and changes in the stability and rate of enzymatic reaction for the encapsulated enzyme versus the non-encapsulated enzyme will be evaluated. It is hypothesised that encapsulation will increase the stability of the enzyme, but may reduce or modify the rate of the catalysed reaction and the reaction scope due to limitations associated with the movement of molecules through the framework material.

Finally, detailed characterisation of the protein within the restricted space of the stabilising framework material will be undertaken and potential opportunities for characterisation of biological proteins that typically display a high degree of disorder or those that are known to operate within a confined space will be evaluated.

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Organisation Website: http://www.man.ac.uk