NanoLife@Work · Real-Time Studies of Biological NanoMachines in Action by NMR
FP7 — People (Marie Curie Actions)
- Duration
- 2012-07-01 → 2014-06-30
- EU contribution
- €201,932
- Participants
- 1
- Scheme
- MC-IEF
Lines connect the coordinator with its partners.
Results in brief
Real-Time Studies of Biological NanoMachines in Action by NMR
Our results help to understand a) mechanism of ATP induced conformational cycle, b) the mechanism of passive substrate protection by chaperone and c) and mechanism of chaperone assisted protein folding, which we are currently nailing down. The knowledge acquired in this project foster the understanding of mechanism chaperones in preventing the accumulation of misfolded of proteins, which are always associated with disease 9 state. The understanding of mechanisms underlying diseases caused by misfolded and aggregated proteins has a great value in finding the strategies to prevent and treat such diseases. The aggregation diseases are growing in occurrence especially in economically developed countries with ageing population and increased life expectancy. The socioeconomic impact of misfolded diseases could be illustrated on Alzheimer’s dementia, which was summarized in the report “Dementia: a public health priority”, which has been jointly developed by WHO and Alzheimer's Disease International.
Data: CORDIS, © European Union
Project objective
Protein Quality Control is an essential and evolutionary-conserved process that is present in all kingdoms of life. In cells, both newly synthesized and pre-existing proteins are constantly prone to misfolding and aggregation. The accumulation of damaged proteins can perturb cellular homeostasis and provoke aging, pathological states and cell death. Accordingly, cells have developed an enzymatic machinery – molecular chaperones – that rescues misfolded proteins by catalyzing their conversion back to the native state in an ATP-dependent manner.In this project, the candidate will use state-of-the-art expertise in NMR spectroscopy to address the fundamental questions of chaperone-assisted protein (re)folding. The combination of cutting-edge techniques in methyl-specific isotope-labeling and fast, relaxation-optimized NMR methods will allow real-time characterization of the molecular events in chaperone activity on an atomic scale. The candidate will exploit the unique potential of this approach to dissect the chaperone oligomerization pathway, ATP-dependent conformation cycle, and chaperone-assisted protein (re)folding.Understanding the mechanism of chaperone action could help in the design of new therapeutic agents for aggregation-related diseases such as Alzheimer’s disease or cystic fibrosis. Furthermore, the development and use of atomic resolution NMR methods for monitoring active ~1 MDa molecular machines will have a huge impact in structural molecular biology.Finally, the candidate will receive first-class training and career development at a major European structural biology centre. The trans-national move to the host institute will help candidate to build international collaborations and acquire new skills and experience. This diversification and enhancement of scientific and professional competences will enable the candidate to reach a position of professional maturity and independence.
Original text from CORDIS.
Participants
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union