!!Rafael Giraldo
!Short laudatio by César Nombela
The whole scientific activity of the Rafael Giraldo (started in 1987 with a PhD studentship) has
been focussed on the study of the interactions between two essential biological
macromolecules: proteins and DNA. A watermark of his research has been the use of
multidisciplinary approaches (Genetics, Biochemistry and Molecular Biology, Biophysics
and Structural Biology) and his focus in microbial model systems (the Gram—negative
bacteria ''Escherichia coli'' and ''Pseudomonas aeruginosa'' and the yeast ''Saccharomyces
cerevisiae''). Along these years, protein-DNA interactions have been studied in the contexts of
DNA replication initiation (Rep and ORC proteins, 1987-2008), telomere structure (Rapl and
DNA—quadruplexes, 1992-1994) and the role of DNA ligands as inducers of protein
amyloidosis (2007—present). This research has been published in 34 papers, many of them in
high impact journals, accumulating over 1500 citations.
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Rafael Giraldo is a national reference in the study of protein-DNA interactions, which is
reflected in being recurrently invited to give talks and advanced courses on this topic in
Spanish universities and research centres, as well as to exert advisory roles for research
agencies (MICINN and ANEP) and societies (SEM, SBE, SEB—BM), He is an internationally recognized leading scientist on bacterial plasmids, as is reflected by his active role in the
International Society for Plasmid Biology and other Mobile Genetic Elements (ISPB) and his
involvement in the activities of the Federation of European Microbiological Societies
(FEMS), including being an Editor of its main journal (''FEMS Microbiol. Rev''.).
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More in detail, over the last 10 years the Rafael Giraldo's group has studied the fundamentals of
DNA—promoted conformational transactions in ''Winged-Helix'' (WH) domains involved in
replication initiation of bacterial plasmids (RepA protein) and yeast chromosomes (Origin
Recognition Complex, ORC). His lab has characterized the large structural switch
experienced by RepA to be enabled as a replication initiator, establishing a paradigm in the
plasmid biology and DNA replication fields. While exploring the molecular basis for RepA
aggregation into replication inhibitory complexes, they recently discovered that a specific
regulatory DNA sequence promotes the assembly of the N—terminal RepA•WH domain into
amyloid fibres. DNA-induced WHs amyloidosis thus mirrors the amyloid pathogenic
transformation (PrP%%sup c/%->PrP%%sup sc/%) underwent by the mammalian prion protein upon binding to ‘
nucleic acids. They have also found small molecules that inhibit amyloidogenesis by binding
to the DNA recognition interface in RepA. These findings have broad implications on human
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Rafael Giraldo's group is developing novel microbial model systems to study ligand
(DNA)—induced amyloid aggregation in bacterial and yeast proteins carrying WH domains.
He expects now to push forward the limits in the current understanding of the molecular basis
for amyloid transformation, and to find new molecules that will inhibit the onset or the
progress of deadly proteinopathies by targeting the binding sites for effectors of amyloidosis.
This provides the grounds for implementing bottom-up ''Synthetic Biology'' approaches, which
aim to the design of modules and devices, based either in natural or artificially modified
macromolecules, enabling novel functionalities in reconstructed or ''de novo ''built—up,
biological systems. In this context, his current research is oriented towards: i) the design of
photo—inducible protein devices and protein-DNA quadruplex hybrid switches to artificially
control amyloid assembly; ii) creation of rron—Mendelian (epigenetic) traits in bacteria
through the development of innovative (harmless) bacterial prions; iii) engineering reliable
protein arrays and microbial sensors for HTS of small molecule inhibitors/effectors of those
processes; and iv) exploring the feasibility of amyloid scaffolds in building novel functional,
self-assembling (orthogonal) microbial modules.


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