Dr. Rafael Giraldo
Department of Cellular & Molecular Biology, CIB-CSIC, Madrid
Untangling amyloid proteinopathies with a synthetic bacterial model system: the RepA-WH1 prionoid
I got a Ph. D. Biol. Sci. in 1991 (Complutense U., Madrid) on the genetics and biochemistry of plasmid DNA replication initiation, under the supervision of R. Díaz-Orejas (CIB-CSIC). Then, I spent a postdoctoral (1992-94) in the group of D. Rhodes at the MRC Laboratory of Molecular Biology (Cambridge, UK), where we studied the role of Rap1 protein in packing telomeric dsDNA, which led to the crystal structure of the first telomeric nucleoprotein complex. We also found that Rap1 promoted the assembly of parallel DNA quadruplexes by the G-rich strand of yeast telomeres, an early example of a protein chaperoning a DNA structure.
Back to CIB-CSIC, first as a postdoctoral (1995-1999) and since then as staff scientist, my main focus was on how sequence-specific DNA binding elicits substantial conformational changes in the winged-helix (WH) domains of plasmid-encoded bacterial replication (Rep) proteins. Besides this, we studied the assembly of yeast ORC initiator. We found in 2007 the way to tailor WH domains to become DNA-modulated amyloidogenic devices, having recently developed synthetic prion-like modules recapitulating essential features of mammalian amyloid proteinopathies (e.g., toxicity, chaperone modulation of conformational strains), albeit confined to a bio-safe bacterial host. Since 2010, I am a CSIC Research Professor and a member of Academia Europaea.