Independent Researcher CONICET / Associate professor (DS) UNC
Phone: +54 351 5353855 ext 3465
E-mail: mcelej@unc.edu.ar
Structure and function of pathological and functional amyloids
Proteins can self-assemble into amyloids, remarkably stable fibrillar nanostructures with a well-defined molecular architecture. Although they were discovered in a pathological context, it is increasingly evident that nature takes advantage of the remarkable properties of these nanostructures for functional purposes. Our line of research is oriented to the study of the thermodynamic, structural and kinetic factors that operate in the adoption and maintenance of the amyloid conformation, investigating the biophysical and biochemical characteristics of pathological and functional amyloids of biomedical interest.
The aggregation of alpha-synuclein and tau (pathological amyloids) is associated with Parkinson’s and Alzheimer’s disease, respectively. We are interested in unreveling the molecular and environmental determinants that modulate the formation of pathogenic species of these proteins, their interrelation and the structural basis of their neurotoxicity.
We have recently become interested in the functional amyloid FapC of P. aeruginosa, an opportunistic pathogen responsible for the formation of infectious biofilms in fibrocystic patients, chronic wounds and contaminants of medical devices. We seek to understand the correlation between functional adaptation and the stability of this amyloid, its mechanism of fibrilogenesis and its immunogenic role.
We employ a multidisciplinary approach that combines genetic engineering, molecular biology, optical spectroscopies(infrared, fluorescence), single molecule techniques (FCS, smFRET) and microscopies(fluorescence, electronic transmission, atomic force). These studies are complemented by cell-based assays designed for evaluating celluar unction and toxicity of these species. roup members develop their projects by discussion with other members of the research team, they are often involved in joint projects with other laboratories and may spend periods of time working with our collaborators in other labs.
Fellows
- Macarena Siri, CONICET posdoctoral fellow
- Nahuel Foressi, SECyT-UNC doctoral fellow
- Leandro Cruz Rodríguez, CONICET doctoral fellow
- Ezequiel Ardanaz, CONICET doctoral fellow
Students
- Melisa Herrera, undergraduate student FCQ-UNC
Selected Publications
- Amyloid oligomerization of the Parkinson’s disease related protein α-synuclein impacts on its curvature-membrane sensitivity. Gallea JI, Ambroggio EE, Vilcaes AA, James A, Jameson DM, Celej MS*. J Neurochem, (2018), 147:541-556
- Structural remodeling during amyloidogenesis of physiological Nα-acetylated α-synuclein. Gallea JI, Sarroukh R, Yunes-Quartino P, Ruysschaert JM, Raussens V, Celej MS. Biochim Biophys Acta (2016), 1864:501-510.
- Structural insights into amyloid oligomers of the Parkinson disease related protein α-synuclein. Gallea JI, Celej MS*. J Biol Chem, (2014), 289:26733-26742.
- Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel beta-sheet structure. Celej MS*, Sarroukh R, Goormaghtigh E, Fidelio GD, Ruysschaert JM, Raussens V. Biochem J, (2012) 443:719-726.
- Protein stability induced by ligand binding correlates with changes in protein flexibility. Celej MS, Montich GG, Fidelio, GD. Protein Sci (2003) 12: 1496-1506.
Grants
- Agencia-FONCyT PICT 2017-0345 (2019-2021)
- SECyT-UNC (2018-2021)
Current Collaborators
- Dr. David Jameson, Dpt. of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai’i at Manoa, USA.
- Dr. Andrés Binolfi, IBR-CONICET.
- Dr. Pablo Iribarren, Depto. Clinical Biochemistry-CIBICI, I. Cs. Chemical, UNC, Argentina.
- Dr. Georgina Fabro, Depto. Biological-Chemical CIQUIBIC, I. Cs. Chemical, UNC, Argentina.
- Dr. Ernesto Ambroggio, Depto. Biological-Chemical CIQUIBIC, I. Cs. Chemical, UNC, Argentina.
Brief CV
Academic Formation
- 2004- PhD in Chemical Sciences, Fcq, UNC. PhD Thesis: Protein stability induced by ligand binding. Characterization of protein conformational states. Advisor: Dr. GD Fidelio. Grade: Outstanding
- 1999- Bachelor in Chemistry, Fcq, UNC. Grade: 8.50/10.0.
Research Background
- 2014-2015: Visiting researcher at Dr. D. Jameson lab., Dept. Cellular and Molecular Biology, University of Hawaii at Manoa, Honolulu, USA. Funding: Fulbright / CONICET
- 2006-2008: Postdoctoral position at Dr. TM Jovin lab., Lab. of Cellular Dynamics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany. Funding: von Humboldt Foundation postdoctoral fellowship
- 2004-2005: Postdoctoral position, at Dr. ST Ferreira lab., Institute of Medical Biochemistry/CCS, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Funding: CNPq postdoctoral fellowship
Teaching Background
- Teaching stuff with more than 17 years of experience at the Dept. Biological Chemistry, College of Chemical Sciences, National Univeristy of Cordoba.
- Undergraduate courses: Biophysical Chemistry, Macromolecule Biochemistry, Molecular and Cell Biology, Advanced Biological Chemistry.
- Graduate, PhD courses
Institutional and R&D Management Background
- 2018-this. Vice-president Argentinean Biophysical Society.
- 2019-present. Member of the Advisory Commission of Biochemistry and Molecular Biology for Reports, Promotions and Projects (CONICET) .
- 2018-present. Member of the Doctorate in Education in Basic Sciences and Technology´s Advisory Board, Fcq, UNC.
- 2016-present. Member of the Doctorate and Master’s Advisory Board, Fcq, UNC.
- 2017-2018. Member of the Advisory Commission of Biochemistry and Molecular Biology for fellowships (CONICET) .
- 2017-2018. Secretary of the Argentinean Biophysical Society
- 2017-2018. Vice-director of Biological Chemistry RC, Fcq, UNC
- 2014-2016. Dept. Biological Chemistry Advisory Board member, Fcq, UNC
- 2011-2016. Member of the Laboratory Practice committee, Fcq, UNC.
- 2011-present. External reviewer in R&D projects (CONICET and Agency-FONCyT) and Research Career of CONICET.
- Reviewer: J. of Luminescence, Bioorganic & Medicinal Chemistry, BBA-Biomembranes, Plos One, J. Neurochemistry.
Awards
- “Most cited paper in Biochem J Knowledge Environment” awarded by Biochemical Journal for the article Celej et al., BJ (2012) 443:719-726
- Special mention “Best Ph.D. Thesis in Biophysics Award 2002-2005”, awarded by the Argentinean Biophysical Society (SAB), 2005.
Human Resources Training
Graduate students
- 2012-2018. Advisor PhD Thesis J. Ignacio Gallea. Grade: Outstanding.
- 2014-2016. Dr Cecilia Challier. Co-Advisor CONICET posdoctoral fellowship.
Bachelor students
- 2017. Advisor final bachelor individual project, Ezequiel Ardanaz.
- 2014-2016. Supervisor undergraduate student, Jacqueline Chanaday Ricagni.
- 2015-2016. Supervisor undergraduate student, Juan Manuel Vargas Fondacaro.
- 2009-2010. Advisor final bachelor individual project, Sebastian Honors.
Internships
- Dr. Rabia Sarroukh, Free University of Brussels (ULB), Belgium, International Cooperation Project granted by CONICET-FNRS. 1/09/14-14/09/14.
- Dr. Adelin Gustot, Free University of Brussels (ULB), Belgium, International Cooperation Project granted by CONICET-FNRS and MINCyT-FNRS. 1/08/13-30/11/13.
- Bioq. Georgina Herrera, National University of South (US), White Bay, Argentina. 1/08/13-30/11/13.
- Biol. Martha Santos, Dept. Anatomy & Cell Biology, College of Medicine, University of Chicago in Illinois, USA. 1/10/12-29/11/12.