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Research Programmes

Structural & Computational Biology

Biomolecular NMR: Structure and dynamics of proteins and protein complexes

Miquel Pons

Miquel Pons

Group Leader
Professor (Organic Chemistry Dept. - UB)
Office Tel : +34 93 40 34683
Lab Tel : +34 93 403 46 77 / +34 93 403 71 32
e-mail : miquel.ponsirbbarcelona.org

Background

Rapidly changing protein-protein interactions play a key role in regulatory processes. These interactions have to be weak in order to be dynamic. This field of study is particularly challenging because it implies the characterisation of equilibria between free and bound forms. It is also an opportunity because these weak interactions can be successfully targeted by drugs.

Research Interests

We use NMR and other biophysical methods, molecular biology techniques, and computational approaches to study the principles of regulatory interactions between macromolecules.

Research Lines

Kinases and phosphatases involved in signalling pathways. We are currently studying the role of the intrinsically disordered Unique domain of human c-Src, a non-receptor protein tyrosine kinase involved in a large variety of signalling cascades. This domain is responsible for the specificity between members of the c-Src kinase family. We are also working with low molecular weight tyrosine phosphatases that reverse the action of kinases. In particular, we have focused on the contribution of the weak self-association of phosphatases to their regulation and the effects of macromolecular crowding inside the cell.

Nucleoid-associated proteins and the regulation of bacterial pathogenicity. The bacterial symbiotic community is necessary for human health but bacteria can also represent a serious threat, especially because of increased resistance to antibiotics. The enterobacteriaceae group includes pathogens of the genus Yersinia, Salmonella, Escherichia, among others. The success of these pathogens is linked to their capacity to selectively regulate horizontally acquired genes, which include the major sources of virulence and antibiotic resistance. Nucleoid-associated proteins are responsible for this selective regulation. A complete understanding of this process would offer the possibility to develop a sustainable strategy to fight infectious diseases by preventing the manifestation of virulence without the extensive use of antibiotics.

Exploiting the richness of chemical space for drug design. The PubChem collection exceeds 26 million compounds. Given its size, this database offers an ideal opportunity to find useful drug candidates; however, the screening of such a large number of compounds is a challenge. With the aim to increase search efficiency, we are exploring the concept of chemical space to identify functional relationships between molecules. Using LINGO methods, developed in our group, we are building the “yellow pages” of PubChem by grouping molecules with expected similar biological functional properties. This computational approach provides a highly efficient and general virtual screening strategy and is complemented with experimental methods.

Methodology. As the reference group of the Spanish National Large Scale NMR facility located in Barcelona, we actively contribute to the development and implementation of new NMR methodology. In particular, members of the group are working in Dynamic Nuclear Polarization and the combined use of NMR and Small Angle X-ray Scattering.

Funding

This group receives financial support from the following sources:

  • Ministerio de Educación y Ciencia (Spanish Ministry of Science and Education)
  • Generalitat de Catalunya (Government of Catalonia)
  • Fundació Marató de TV3
  • European Science Foundation
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  • Generalitat de catalunya
  • Generalitat de catalunya. Salut
  • Universidad de Barcelona
  • Parc cientific

Institute for Research in Biomedicine (IRB Barcelona)
Parc Científic de Barcelona
C/ Baldiri Reixac 10
08028 Barcelona - Spain
Tel: +34 93 402 02 50 | Fax: +34 93 403 71 14
infoarrobairbbarcelona.org