Independent Researcher CONICET / Associate Professor (DS) UNC
Phone: +54 351 5353855 ext 3465
Protein misfolding and amyloid aggregation
Several pathologic conditions arise from the misfolding of polyeptides that aggregate into amyloid fibrils, highly organized supramolecular beta-sheet-rich structures. Many of these conditions are neurodegenerative with high socioeconomic impact, such as BSE and Alzheimer’s (AD) and Parkinson’s (PD) diseases. Our line of research is aimed at studying the molecular, kinetic and environmental parameters that lead to misfolding and amyloid aggregation of proteins and their relationship to cell dysfunction. We are particularly interested in the molecular bases underlying systemic amyloidosis and neurodegenerative diseases, with special emphasis on PD. Prefibrillar amyloid oligomers are pointed as the most neurotoxic species. A hypothetical mechanism for toxic is membrane damage. Within this framework we are currently studying amyloid oligomers of α-synuclein, key protein in PD pathogenesis, at the molecular level. We focus on 1) the structure and supramolecular organization of α-synuclein oligomers; 2) the interaction with model membrane systems and 3) the loss of function associated with self-aggregation. Recently, we have become interested in the effect of point mutations and posttranslational modifications in α-synuclein that increase amyloid propensity. We want to establish the physicochemical bases of such behavior.
We employ a multidisciplinary approach that combines genetic engineering, molecular biology, optical spectroscopies, single molecule techniques and microscopies. These studies are complemented by cell-based assays directed at evaluating the effect of amyloid aggregates in ion permeation, seeding and cell viability. The group has close links with scientists in other laboratories in the country and abroad. Group 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.
- Jose Ignacio Gallea
- Cecilia Challier (National University of Rio IV). Co-advisor postdoctoral fellowship from CONICET.
- 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.
- Small molecule fluorescent probes for the detection of amyloid self-assembly in vitro and in vivo. Bertoncini CW *, Celej MS*. Curr Prot and Peptide Sci (2011) 12:205-220.
- Protein stability induced by ligand binding correlates with changes in protein flexibility. Celej MS, Montich GG, Fidelio, GD. Protein Sci (2003) 12: 1496-1506.
- Agencia-FONCyT PICT 2013-2603 (2014-2017)
- SECyT-UNC (2016-2017)
- Dr. David Jameson, Dpt. of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai’i at Manoa, USA.
- Dr. Carlos Bertoncini, Innovation Projects Director DOMINGUEZLAB), Argentina.
- 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.
- 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.
- 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 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 Management Background
- 2014-present. Dept. Biological Chemistry Advisory Board member, Fcq. UNC
- 2015-present. Member of the PhD dissertation commitee of Lic. Luis Benito Perez Socas, Fcq, UNC.
- 2011-present. 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
- “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
- Biol. J. Ignacio Gallea. PhD student. 2012-present
- Dr Cecilia Challier. Co-Advisor CONICET posdoctoral fellowship. 1/04/2014-31/03/2016.
- Jacqueline Chanaday, undergraduate student. 2014-present.
- Juan Manuel Vargas Fondacaro, undergraduate student. 2015-present.
- Sebastian Honors, final bachelor individual project. 08/2009-07/2010.
- 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.