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Projects. Life and Earth Sciences

Modification of the folding and function of mutated opsins by cellular factors as a new therapeutic strategy for degenerative diseases of the retina

Lead Researcher:
Pere Garriga Solé

Research Centre:
Universidad Politécnica de Cataluña. Barcelona.

Synopsis: 

Pere Garriga SoléMutations in rodopsin are the chief cause of dominant autosomal pigmentary retinosis (PR). These mutations may be classified according to their biochemical and cellular properties. The folding, degradation and aggregation of some of these mutated rodopsins may be modified using drugs and molecular chaperones. Likewise, mutations in the opsins of the photoreceptor cone cells cause the dystrophy of cones and rods. The main aim of this project is to understand the molecular mechanism(s) of poor folding of the rodopsin and of the cone opsins induced by genetic mutations, and to verify the hypothesis that some drugs and molecular chaperones may affect the destination of the mutated opsins.

To date, work has taken place on the first specific objective of the work plan: to determine the effect of mutations on genes associated with PR and the dystrophy of cones and rods in the structure (folding), stability (degradation and structural instability) and function (the activation and deactivation of the process of visual phototransduction).

In particular, targeted mutagenesis has made it possible to obtain the following mutations in the opsin gene associated with PR: N55K, M39R and T193M, among others, and the mutations of cone opsins: G338E (red cone opsin), W177R and R330Q (green cone opsin) associated with cone dystrophy.

These mutated genes were expressed in COS-1 eukaryotic cell cultures and purified by immunoaffinity chromatography using the Rho‑1D4 monoclonal antibody for rodopsin. It should be pointed out that in the case of cone opsins the 9 amino acid epitope (TETSQVAPA) was added at the C-terminal end of the protein to recognise the rodopsin antibody and ensure its efficient purification. The first results obtained indicate that some of the mutations cause poor folding of the proteins, but in some cases the defect may be associated with alterations in the response to illumination during the process of activating the photoreceptor.


Scientific production
1 paper at national conferences
6 papers at international conferences

 

Researcher's web address:
http://www.recercaterrassa.upc.edu/node/44



Pere Garriga Solé

Doctor in Chemistry from the Autonomous University, Barcelona. Post-doctoral stays and as a visiting scientist in the Chemistry and Biology Departments of Massachusetts Institute of Technology, in the laboratory of Prof. H. Gobind Khorana, a Nobel Prize-winner for Medicine or Physiology. He is currently Professor of the Department of Chemical Engineering in the Polytechnic University of Catalonia (UPC) and is a member of the Optic and Optometric Faculty of Terrassa, where he teaches most of his classes. His research centres on the area of molecular biotechnology, more particularly on the study of membranes which are of biomedical or pharmacological interest, such as the receptors coupled to G proteins. More specifically, some of his research work has aimed to clarify the molecular bases for a degenerative disease of the retina, pigmentary retinosis, associated with mutations in the rodopsin protein of the photoreceptor cells of the retina. The results obtained in this field have made it possible to propose new mechanisms and confirm the highly heterogeneous nature of the disease.

He is the co-ordinator of the consolidated research group "Molecular and Industrial Biotechnology Group", and is the Director of the Centre for Molecular Biotechnology of the UPC. He was recently Visiting Professor in University College, London, and Fellow of the Hanse-Wissenschaftskolleg, Delmenhorst, Germany.


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