| EPSRC Reference: |
EP/H020616/1 |
| Title: |
Biophysics of cryopreservation: elucidating the structural architecture and physical mechanisms of both model and complex biological systems |
| Principal Investigator: |
Dougan, Professor L |
| Other Investigators: |
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| Researcher Co-Investigators: |
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| Project Partners: |
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| Department: |
Physics and Astronomy |
| Organisation: |
University of Leeds |
| Scheme: |
First Grant - Revised 2009 |
| Starts: |
25 February 2010 |
Ends: |
20 August 2012 |
Value (£): |
100,052
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| EPSRC Research Topic Classifications: |
| Chemical Biology |
Complex fluids & soft solids |
| Scattering & Spectroscopy |
Surfaces & Interfaces |
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| EPSRC Industrial Sector Classifications: |
| Pharmaceuticals and Biotechnology |
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| Related Grants: |
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| Panel History: |
| Panel Date | Panel Name | Outcome |
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02 Oct 2009
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Physical Sciences Panel- Physics
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Announced
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Summary on Grant Application Form |
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Many organisms that live in extreme environments have developed mechanisms that protect them from environmental stresses such as low temperatures. Cryopreservation is an effective process where cells or whole tissues are preserved by cooling to sub-zero temperatures. The cryoprotectant molecule glycerol is ubiquitous in living systems where it plays a vital role in stabilizing organisms against adverse environmental conditions. Glycerol's role as a cryoprotectant is most likely linked to the interactions between glycerol, the organism and bulk water environment. Understanding the molecular interactions of the glycerol/water system itself is a necessary first step toward understanding higher complexity systems in glycerol solutions. Uncovering the full potential of cryopreservation therefore heavily relies on improving our understanding of the physical interactions and molecular mechanisms involved. These mechanisms determine the structural architecture of the system of interest and ultimately the dynamics of subsequent biological and chemical reactions. Taking a structural approach to first determine the principles of cryopreservation in simple systems such as an aqueous cryoprotectant system, will provide initial molecular models. Extending these models to real biological systems, such as protein folding in cryoprotectant environments will provide a means to test, refine and develop these models. To begin with, I will explore a simple cryoprotectant system, aqueous glycerol, using an experimental technique called neutron diffraction. This technique provides information on the structural properties of the system. Next, I will explore the physical mechanisms of cryoprotectants in a more complex system. I will examine the folding and unfolding properties of individual proteins in different cryoprotectant environments. The experimental technique I will utilize is single molecule force-clamp spectroscopy. In force-clamp spectroscopy a single protein molecule is held at a constant stretching force, such that the unfolding and refolding processes can be observed as a function of time. I will develop and construct a custom-built force-clamp instrument at the University of Leeds. I will use this instrument to mechanically unfold single proteins at a constant force and examine the physical properties of protein unfolding.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
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| Date Materialised |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.leeds.ac.uk |