MAIN RESEARCH LINE
Carlos Fernández Tornero works in this field since 2002, when he started his postdoctoral research at EMBL-Grenoble (France). He continued in 2007 when appointed staff scientist at EMBL-Heidelberg (Germany). In 2009 he moved to the CIB and since 2011 he leads an independent research line as group leader, combining X-ray crystallography and electron microscopy to study complexes involved transcription.
Eukaryotic cells have three RNA polymerases (Pol) to transcribe their genetic content. Pol I synthesizes ribosomal RNA, Pol II produces all messenger RNA, and Pol III is responsible for transfer RNA. Coordination of these three enzymes is essential to maintain cellular homeostasis.
Pol I is a complex of 14 proteins with a total mass of 600 kDa, responsible for synthesizing the core of the ribosome. Regulation defects in Pol I transcription associate with problems in cell proliferation and, hence, with tumor development. We have determined the structure of this enzyme to 3 Å resolution using X-ray crystallography. The atomic structure explains fundamental properties of the enzyme, such as the incorporation of functional modules that must be recruited in other Pols, while suggesting a unique activation mechanism. These results were recently published in Nature and appeared in national and international media.
Pol III, consisting of 17 subunits with a total mass of 700 kDa, transcribes several small RNA genes such as transfer RNA. We have determined the structure of this macromolecular complex to 10 Å resolution using electron cryomicroscopy, both in the presence and absence of nucleic acids. These studies, in combination with native mass spectrometry experiments, have enabled us to understand the architecture and organization of this essential enzyme. These results were published in The EMBO Journal and RNA Biology, highlighted on the journal cover in the latter case.
COMPLEMENTARY RESEARCH LINES
Carlos Fernández Tornero collaborates with other groups in the EM and X-ray structural determination of essential cellular complexes. One such case is glutamine synthetase, critical for nitrogen fixation in plants. We recently determined the cryo-EM structure of plastidial glutamine synthetase, a decameric enzyme organized in two pentameric rings that interact weakly. Our EM data suggest that partially-active pentameric rings assemble in a zipper-like manner to generate the fully active decameric organization. These results were published in Acta Crystallographica section D and highlighted on the journal cover.
Clinical applications against angiogenic diseases
Guillermo Giménez-Gallego was a member of the team that described the first angiogenic growth factor (FGF). Later he spent considerable effort in discovering inhibitors of FGF and at the end of 2010 he described a family of potent inhibitors derived of gentisic acid (GA). Meanwhile it was discovered that FGF induces angiogenesis as it triggers inflammation. The inhibitors of the GA family have shown, in the clinic, a remarkable capacity of controlling some inflammations, such as those causing macular degeneration