| EPSRC Reference: |
EP/G026165/1 |
| Title: |
Heterogeneous nucleation of polypeptide chains |
| Principal Investigator: |
Auer, Dr S |
| Other Investigators: |
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| Researcher Co-Investigators: |
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| Project Partners: |
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| Department: |
Centre for Molecular Nanoscience |
| Organisation: |
University of Leeds |
| Scheme: |
First Grant Scheme |
| Starts: |
01 March 2009 |
Ends: |
30 November 2012 |
Value (£): |
414,945
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| EPSRC Research Topic Classifications: |
| Bionanoscience |
Chemical Biology |
| Structural biology |
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| EPSRC Industrial Sector Classifications: |
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| Related Grants: |
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| Panel History: |
| Panel Date | Panel Name | Outcome |
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19 Nov 2008
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Chemistry Prioritisation Panel November
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Announced
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Summary on Grant Application Form |
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The main goal of this project is to reveal the physical aspects of theheterogeneous nucleation of polypeptide chains into amyloid-likestructures. The assembly of proteins into highly ordered structures,known as amyloid, is a much studied phenomenon because of itsimplications for human health and nanoscience.Increasing evidence shows that protein aggregation is associated withvarious neurological and systemic diseases.Neurodegenerative diseases can affect abstract thinking, skilledmovements, emotional feelings, memory and other abilities. Prominentexamples of this diverse group of conditions include Alzheimer's andParkinson's diseases. Proteins that accumulate in tissues as fibrillardeposits can be toxic to cells, but despite thewidespread occurrence of amyloid-related diseases, molecular insightinto the aggregation mechanism and the fibril mediated toxicity isdifficult to obtain. On the other hand, the abilityto control biomolecular assembly into well-ordered nanostructuresrepresents the essence of modern nanotechnology. Peptides can assembleinto nanotubes, nanospheres, nanofibrils, nanotapes, and applicationsof peptide building blocks in bio-sensors, tissue engineering, andantibacterial agents have already been demonstrated. Here we propose to investigate by computer simulation how thenucleation of peptides is influenced by external factors. Inparticular we focus on: (i) ``foreign'' seeds such as impurities orother molecules that might act as templates, (ii) cell membranes suchas lipid bilayers to investigate the toxicity of amyloidogenicproteins, (iii) fibrillar seeds to provide insight into the molecularbasis of strain polymorphism and species barriers in amyloid andprions. The complexity of the systems requires a simplifying approach,and statistical mechanics and coarse grained modelling are essential.The ultimate goal of the project is to unify the current outbreak ofexperimental and theoretical studies on protein aggregation to providea theoretical framework of the nucleation mechanism on the basis ofthe physical properties of proteins and well understood concepts frompolymer physics.
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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 |