Alfredo De Biasio

Personal Details

Dr. Alfredo De BiasioLecturer in Structural Biology

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Telephone: +44 (0)116 252 5391
Department: Molecular and Cell Biology
Email: adb43@leicester.ac.uk
Web links:

Biography

I am a lecturer in Structural Biology. I own a M.Sc. in Chemistry from the University of Padua, Italy, and a Ph.D. from the International Centre for Genetic Engineering and Biotechnology in Trieste, Italy (obtained in 2008). Most of my postdoctoral work, mainly carried out at CIC bioGUNE in Spain, has been devoted to the study of the structure and function of DNA replication proteins, in particular of the human sliding clamp PCNA and its complexes. In 2015, I have been awarded a 2-year AIRC-Marie Curie Reintegration Fellowship from the Italian Association for Cancer Research to work at Elettra-Sincrotrone Trieste, Italy, where I coordinated an international project involving three laboratories. The results of this project, which combined experimental and computational methods, have provided a structural basis for the mechanism of PCNA sliding on DNA, and resolved a long-lasting controversy on how eukaryotic clamps recognize and bind the DNA double helix. In 2017, I joined the University of Leicester, where I continue exploring the architecture and function of DNA replication and repair machines.

Qualifications

  • M.Sc., University of Padua, Italy
  • Ph.D., International Centre for Genetic Engineering and Biotechnology, Italy

Publications

  1. De March M. & De Biasio A. (2017) “The dark side of the ring: role of the DNA sliding surface of PCNA”, Crit. Rev. Biochem. Mol. Biol. Aug 17:1-11.
  2. De March M., Merino N., Barrera-Vilarmau S., Crehuet R., Onesti S.*, Blanco F.J.* and De Biasio A.* (2017) “Structural basis of human PCNA sliding on DNA” Nat. Commun. 7, 13935**
  3. Article above reviewed in Yao N. and O'Donnell M. “DNA Replication: How Does a Sliding Clamp Slide?” (2017) Curr. Biol. 27(5):R174-R176
  4. Cordeiro T.N., Chen P., De Biasio A., Sibille N., Blanco F.J., Hub J.S., Creuhet R. and Bernadó P. (2017) “Disentangling polydispersity in the PCNA‒p15PAF complex, a disordered, transient and multivalent macromolecular assembly” Nucleic Acids Res. 45(3):1501-1515
  5. De Biasio A.*, Ibañez de Opakua A., Mortuza G., Molina A., Cordeiro T.N., Castillo F., Villate M., Merino N., Delgado S., Gil-Cartón D., Luque I., Diercks T., Bernadó P., Montoya G. and Blanco F.J.* (2015) “Structure of p15PAF‒PCNA complex and implications for clamp sliding during DNA replication and repair” Nat. Commun. 6:6439
  6. De Biasio A., Ibáñez de Opakua A., Cordeiro T.N., Villate M., Merino N., Sibille N., Lelli M., Diercks T., Bernadó P., Blanco F.J. (2014) “p15PAF is an intrinsically disordered protein with nonrandom structural preferences at sites of interaction with other proteins” Biophys. J. 106(4):865-74
  7. De Biasio A. and Blanco F.J. (2013) “Proliferating Cell Nuclear Antigen (PCNA) Structure and Interactions. Too Many Partners for One Dancer?”, Adv. Protein Chem. Struct. Biol. 91:1-36
  8. Kolyada A., De Biasio A. and Beglova N. (2013) “Identification of the binding site for fondaparinux on Beta2-glycoprotein I” Biochimica et Biophysica Acta 1834(10):2080-2088
  9. De Biasio A., Campos-Olivas R., Sánchez R., López-Alonso J.P., Pantoja-Uceda D., Merino N., Villate M., Martín-García J.M., Castillo F., Luque I., and Blanco F.J. (2012) “Proliferating Cell Nuclear Antigen (PCNA) interactions in solution studied by NMR”, PLoS ONE 7(11): e48390
  10. Nifoussi S.K., Vrana J.A., Domina A.M., De Biasio A., Gui J., Gregory M.A., Hann S.R., Craig R.W. (2012) “Thr 163 phosphorylation causes Mcl-1 stabilization when degradation Is independent of the adjacent GSK3-targeted phosphodegron, promoting drug resistance in cancer”, PLoS One 7(10): e47060
  11. De Biasio A., Sánchez R., Prieto J., Campos-Olivas R., Blanco F.J. (2011) “Reduced stability and increased dynamics in the human proliferating cell nuclear antigen (PCNA) relative to the yeast homolog”, PLoS ONE 6(2): e16600
  12. Kolyada A., Lee C.J., De Biasio A. and Beglova N. (2010) “A novel dimeric inhibitor targeting Beta2GPI in Beta2GPI/Antibody complexes implicated in Antiphospholipid Syndrome”, PLoS One 5(12): e15345
  13. Lee C.J., De Biasio A., Beglova N. (2010) “The mode of interaction between B2GPI and lipoprotein receptors suggests that the binding of B2GPI to the receptors and anionic phospholipids is mutually exclusive” Structure 18(3):366-76
  14. Beglov D., Lee C.J., De Biasio A., Kozakov D., Brenke R., Vajda S. and Beglova N. (2009) “Structural insights into recognition of beta2-glycoprotein I by the lipoprotein receptors”, Proteins 77(4):940-9
  15. De Biasio A., Guarnaccia C., Popovic M., Uversky V.N., Pintar A. and Pongor S. (2008) “Prevalence of Intrinsic Disorder in the Intracellular Region of Human Single-Pass Type I Proteins: The Case of the Notch Ligand Delta-4” Journal of Proteome Research 7(6):2496-506
  16. Popovic M., De Biasio A., Pintar A. and Pongor S. (2007) “The intracellular region of the Notch ligand Jagged-1 gains partial structure upon binding to synthetic membranes”, FEBS Journal 274(20):5325- 36
  17. Pintar A., De Biasio A., Popovic M., Ivanova N. and Pongor S. (2007) “The intracellular region of Notch ligands: does the tail make the difference?” Biology Direct 2:19
  18. De Biasio A., Vrana J.A., Zhou P., Qian L., Bieszczad C.K., Braley K.E., Domina A.M., Weintraub S.J., Neveu J.M., Lane W.S. and Craig R.W. (2007) “N-terminal truncation of antiapoptotic MCL1, but not G2/M-induced phosphorylation, is associated with stabilization and abundant expression in tumor cells” Journal of Biological Chemistry 282(33):23919-36

Research

The genetic information is encoded in long chains of deoxyribonucleic acid (DNA) molecules packaged into chromosomes in the cell nucleus. Before dividing, cells need to accurately duplicate their DNA, to ensure that each daughter cell has an identical copy. Critical players in DNA replication are the so-called DNA clamps, ring-shaped proteins that slide on the DNA double helix and anchor the polymerases, the enzymes that replicate DNA, to the genomic template. Beside DNA replication, sliding clamps function in the DNA damage response and the maintenance of genome integrity. Due to their central role in cell proliferation, DNA clamps are an important hallmark of tumors, as well as potential drug targets for anti-cancer therapy.

Our aim is to unravel the molecular architecture of eukaryotic DNA replication complexes involving DNA sliding clamps, and to shed light on their inner workings. To tackle these composite, supramolecular assemblies we integrate structural (X-ray, NMR, Cryo-Electron Microscopy), biochemical and computational methods.

In our work, we have determined the structure of the human clamp PCNA bound to p15PAF, a modulator of the DNA damage tolerance pathway, revealing a unique mode of binding with functional implications. Our work has also provided a structural basis for the mechanism of PCNA sliding on DNA, resolving a long-lasting controversy on how eukaryotic clamps recognize and bind the DNA double helix.

An important focus of our current research is the integration of the structural studies with single- molecule studies, to resolve the spatio-temporal processes directed by PCNA. To this purpose, we are collaborating with the laboratory of Jong-Bong Lee, at Postech University.

> See my LISCB research page.

Supervision

A PhD position for a EU/UK student is currently available in my lab. More information on this position can be found here.

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Contact Details

Department of Molecular and Cell Biology

T: +44(0)116 229 7038
E: MolCellBiol@le.ac.uk

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