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Protein folding, misfolding and protein disease

Research project

The research program is focused on the fundamental, molecular aspects of protein folding, misfolding and aggregation, and is based on “biophysical” analysis of genetically modified and re-designed proteins with a comprehensive range of experimental techniques.

Project overview

Project period

2007-04-03 2007-07-01

Funding

Finansår , 2004, 2005, 2006

huvudman: Mikael Oliveberg, finansiar: Vetenskapsrådet -NT, y2004: 1080, y2005: 1080, y2006: 1080,

huvudman: Mikael Oliveberg , finansiar: Vetenskapsrådet - M, y2004: 416, y2005: 416, y2006: ,

huvudman: MO , finansiar: Göran Gustafssonpriset, y2004: 1500, y2005: 1500, y2006: 1500,

Research subject

Chemical sciences, Pharmaceutical science

Project description

Our projects are directed along the following lines:
- Studies of the folding nucleus and the folding energy landscape and how these respond to changes in topology (natural and tailor made) and amino-acid composition. A central objective is to identify the features of the folding reaction that are controlled by biology (i.e. evolved features) and those that are limited by the folding physics.
- Studies of conformational gatekeepers – the role of some conserved residues is not primarily to form native contacts but to control misfolding and aggregation through negative design.
- Folding in confined space. In the cell, folding often occurs in confined space but there are hardly any data on how conformational restrictions affect protein stability and folding cooperativity.
- Studies of pathogenic fibrillation processes with specific focus on the role of sequence “stickiness”, protein stability and native-state plasticity. The project is also aimed at design of protein and peptide constructs with well defined aggregation pathways for in vivo studies.
- Common denominators of Cu/Zn SOD mutations associated with ALS. Recent indications of a folding related cause of ALS as well as new methods to rationally produce SOD mutants have open the door to a large-scale effort on the ALS mechanism.