Connecting European Neuroscience

Magdalini Polymenidou

Programme Committee Member FENS Forum 2020

Curriculum Vitae

Professional and Academic Career

EDUCATION

  • 2006: PhD in Natural Sciences (Dr. sc. nat. ), University of Zurich
  • 2001: Diploma in Pharmaceutical Sciences, Aristotle University of Thessaloniki

CURRENT & PREVIOUS POSITIONS

  • Since 2013: Swiss National Science Foundation (SNSF) Assistant Professor, University of Zurich, Switzerland
  • 2008-2013: Postdoctoral Fellow, Department of Cellular and Molecular Medicine, UCSD, USA
  • 2006-2008: Postdoctoral Fellow, University of Zurich, Switzerland.

Honours and Awards

  • 2018: “45 below 45” most highly cited Greek scientists below the age of 45
  • 2018: EMBO Young Investigator Program
  • 2018: US Department of Defense Therapeutic Idea Award, (with C. Lagier-Tourenne)
  • 2017: ALSA Investigator Initiated Award
  • 2017: SNSF Sinergia Grant (with F. Allen, B. Schuler & G. Jeschke)
  • 2017: Target ALS Industry-led Consortium, (with C. Lagier-Tourenne, L. Ranum & Neurimmune)
  • 2015: NCCR RNA & Disease Junior Investigator Award
  • 2015: Georg-Friedrich Götz Prize
  • 2015: ZUNIV Research Talent Development Fund
  • 2013: HFSP Career Development Award
  • 2011: NIH Pathway to Independence Award K99, Best Priority Score: 10
  • 2008: HFSP Long Term Postdoctoral Fellowship
  • 2008: SNSF Fellowship for advanced researchers (gratefully declined)
  • 2005: UZH Career Award
  • 2001: EMBO Short Term Fellowship

General Administrative and Organisational Experience

  • 2013-2018: Coordinator of Gender Equality Committee, Neuroscience Center Zurich, University and ETH
  • Since 2014: Elected member, Steering Committee, Neuroscience Center Zurich, University and ETH Zurich
  • Since 2014: Member, Steering committee, RNA biology PhD program, Life Science Graduate School Zurich
  • 2016: Organizer of Zing Conference on Propagation in Neurodegenerative Disease, Dublin, Ireland, 8th-11th August; co-chair with J. Ravits: http://www. zingconferences. com/gallery/
  • 2017: Organizer of Joint Forces Symposium on Reversible and Pathological Aggregates in Health and Disease, Zurich, Switzerland, 19th-20th June; co-chair with M. Peter & P. Picotti: http://www. joiningforces.ethz.ch/programme. html.

Research Interests

My research is centered on molecular mechanisms of neurodegenerative diseases and my overarching goal is the development of mechanism-based therapies. My team’s work is focused on amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which are fatal and incurable neurodegenerative diseases, characterized by accumulation of RNA-binding proteins such as TDP-43 and FUS. In the most common genetic form of these diseases, non-canonical RNA translation leads to the production of dipeptide repeat proteins (DPRs), which are abnormal and toxic proteins. The molecular mechanisms that trigger aggregation of ALS/FTD-linked proteins, the basis of disease heterogeneity and the mechanisms of neurotoxicity remain elusive. Our vision is to address these important mechanistic questions using a multidisciplinary approach, by combining biochemical and structural protein analysis with cellular assays to unravel the physiological and pathological states of the most important protein players in ALS and FTD. Moreover, we use mouse organotypic slice cultures and multilayer human neuronal networks to understand the initial steps of cytoplasmic protein aggregation and to build models with faithful ALS/FTD-like pathology and neurodegeneration.

Selected Publications

1. Loughlin F, Lukavsky P, Kazeeva T, Reber S, Hock EM, Colombo M, Pauli P, von Schroetter C, Muhlemann O, Polymenidou M, Ruepp MD, Allain FHT (2018) The solution structure of FUS bound to RNA reveals a bipartite mode of RNA recognition with both sequence and shape specificities, Molecular Cell, doi: 10.1016/j.molcel.2018.11.012

2. Laferriere F*, Maniecka Z*, Pérez-Berlanga M, Hruska-Plochan M, Gilhespy L, Wagner U, Afroz T, Boersema PJ, Barmettler G, Foti SC, Asi Y T, Isaacs A, Al-Amoudi A, Lewis A, Stahlberg H, Ravits J, De Giorgi F, Ichas F, Bezard E, Picotti P, Lashley T, Polymenidou M (2019) TDP-43 extracted from FTLD patient brains displays distinct aggregate assemblies and neurotoxic effects reflecting disease progression rates, Nature Neuroscience, 22, 65-77

3. Hock EM, Maniecka Z, Hruska-Plochan M, Reber S, Laferriere F, Sahadevan, SMK, Ederle H, Gittings L, Pelkmans L, Dupuis L, Lashley T, Ruepp M, Dormann D, Polymenidou M (2018) Hypertonic stress causes cytoplasmic translocation of neuronal but not astrocytic FUS due to impaired Transportin function, Cell Reports, 24, 987-1000. e7

4. Polymenidou M (2018) The RNA face of phase separation Science, 360, 859-860

5. Foglieni C, Papin S, Salvade A, Afroz T, Pinton S, Pedrioli G, Ulrich G, Polymenidou M, Paganetti P (2017) Split GFP technologies to structurally characterize and quantify functional biomolecular interactions of FTD-related proteins, Scientific Reports, 7, 14013

6. Afroz T, Hock EM*, Ernst P*, Jambeau M, Foglieni C, Laferriere F, Gilhespy L, Maniecka Z, Pluckthun A, Mittl P, Paganetti P, Allain FHT, Polymenidou M (2017) Functional and dynamic polymerization of the ALS-linked protein TDP-43 antagonizes its pathologic aggregation Nature Communications, doi: 10.1038/s41467-017-00062-0

7. Lagier-Tourenne C*, Polymenidou M*, Hutt KR*, Vu AQ, Clutario K, Baughn M, Huelga SC, Ling SC, Liang TY, Mazur C, Wancewicz E, Kim AS, Watt A, Freier S, Hicks GG, Donohue JP, Shiue L, Bennett CF, Ravits J, Cleveland DW and Yeo GW (2012) Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs, Nature Neuroscience, 15, 1488-97

8. Polymenidou M, Cleveland DW (2011) The Seeds of Neurodegeneration: Prion-like Spreading in ALS Cell, 147, 498-508

9. Polymenidou M*, Lagier-Tourenne C*, Hutt KR*, Huelga SC, Moran J, Liang TY, Ling SC, Sun E, Wancewicz E, Mazur C, Kordasiewicz H, Sedaghat Y, Donohue JP, Shiue L, Bennett CF, Yeo GW, Cleveland DW (2011) Long premRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43 Nature Neuroscience, 14, 459–468

10. Heikenwalder M*, Polymenidou M*, Junt T, Sigurdson C, Wagner C, Akira S, Zinkernagel R, Aguzzi A (2004) Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration Nature Medicine, 10, 187-92.

Magdalini Polymenidou

Swiss National Science Foundation (SNSF) Assistant Professor
Department of Quantitative Biomedicine, University of Zurich, Switzerland
Double appointment, Faculty of Natural Sciences and Faculty of Medicine.

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