People

Dr Cyril Dominguez

Associate Professor in Structural Biology

School/Department: Molecular Cell Biology, Department of

Telephone: +44 (0)116 229 7073

Email: cd180@leicester.ac.uk

Profile

I am a structural biologist interested mainly in protein-RNA interactions involved in the regulation of alternative splicing. I obtained my BSc and MSc in Biochemistry from the University of Aix-Marseille (France). In 2000 I moved to the University of Utrecht (The Netherlands) to do a PhD under the supervision of Rob Kaptein Rolf Boelens and Alexandre Bonvin. During that time I developed a novel protein-protein docking software HADDOCK. After my PhD in 2004 I joined the laboratory of Fred Allain at the ETH Zurich (Switzerland) where I studied the interaction between the splicing factor hnRNP F and G-tract RNAs. In 2010 I obtained an MRC Career Development Award Fellowship to initiate my own research programme at the University of Leicester. My research focused on i) the interaction between the splicing factor Sam68 and its target RNA and ii) the role of RNA G-quadruplexes in the regulation of alternative splicing. In 2015 I became a lecturer at the University of Leicester.

Research

Alternative splicing of pre-mRNA is a centrally important and extraordinary cellular process that allows the generation of proteomic diversity from only 20000 human genes.The process of alternative splicing is very complex and still poorly understood. It is regulated by many proteins called splicing factors that may either enhance or prevent the recognition of a particular splice site in a time cell-type and cell-cycle dependent manner. Cell signalling also plays a major role in the regulation of alternative splicing through post-translational modifications of splicing factors demonstrating a tight link between cell signalling and alternative splicing regulation.

Our research interest is to understand at the molecular level the role of splicing factors on alternative splicing. Additionally we are interested in the role of pre-mRNA secondary and tertiary structures on alternative splicing regulation.

To this aim we are studying RNA protein-protein and protein-RNA complexes using structural biology techniques (NMR and X-ray) biophysical methods (ITC Fluorescence polarization) and biochemical methods (RNA footprinting EMSA).

Publications

(0) Weldon C,. Dacanay J.G., Gokhale V., Boddupally P.V.L., Behm-Ansmant I., Burley G.A., Branlant C., Hurley L.H., Dominguez C., Eperon I.C. (2018). Specific G-quadruplex ligands modulate the alternative splicing of Bcl-x. Nucleic Acids Res., 46, 886-96

Weldon C., Behn-Ansmant I., Burley G.A., Hurley L.H., Branlant C., Eperon I.C., and Dominguez C. (2016). Identification of G-quadruplexes using 7-deaza-guanine substituted RNA. Nat. Chem. Biol., 13, 18-20

Feracci M., Foot J.N., Grellscheid S.N., Danilenko M., Stehle R., Gonchar O., Kang H.S., Meyer N.H., Liu Y., Lahat A., Sattler M., Eperon I.C., Elliott D.J., and Dominguez C. (2016). Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68. Nat. Comms, 7, 10355.

Supervision

Gene expression structural biology NMR

Teaching

BS3070: Structural Biology. Co-convenor and Lecturer onNMR

BS3010: Gene expression. Lecturer on protein-RNA interactions

MB2050: Medical Biochemistry.

Lecturer on drug screening and design

MSc Bioinformatics: Lecturer on Protein structure and NMR 

Media coverage

https://www2.le.ac.uk/offices/press/press-releases/2016/november/new-advance-in-rna-studies- holds-out-hope-for-cancer-drug-development

https://www2.le.ac.uk/offices/press/press-releases/2016/january/new-study-creates-first-3d- vision-of-cancer-target

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