FY2023 Annual Report

FY2023 Annual Report

Molecular Neuroscience Unit
Assistant Professor Marco Terenzio

 

  • (From left to right) Lower row: Akiko Guzman, Miki Otsuki, Susan Boerner, Laurent Guillaud, Sara Emad El-Agamy Abdelaal, Marco Terenzio, Sandra De La Fuente Ruiz, Sarah Zakhia, Fregoso Fernandez Esteban Gabriel, Amy Xia Yi Yong, Maria Fransiska Emily, Yuto Akimoto.

Abstract

In 2023 we have charcterized the interaction between the Dynlrb1 subunit of the molecular motor dynein and the FMRP RNA binding protein in sensory neuron axons. This work resulted in a pubblication and was the basis for the Ph.D. graduation of Emad El-Agamy Abdelaal. We also continued our investigation of both axonal translation after injury and the mechanism underlying axonal degeneration in ALS using human iPSC. We have also applied to EMBO for orgnanizing an EMBO workshop at OIST in 2024 and were granted the applicatrion.

1. Staff

  • Assistant Professor Marco Terenzio, Unit Leader
  • Dr. Laurent Guillaud, Group Leader
  • Dr. Madeleine Le Coz, Post-doctoral Scholar
  • Dr. Sandra De La Fuente Ruiz, Post-doctoral Scholar
  • Sara Emad El-Agamy Abdelaal, Ph.D. Student
  • Maria Fransiska Emily, Ph.D. Student
  • Sarah Zakhia, Ph.D. Student
  • Maria Fernanda Bolanos Alejos, Ph.D. Student
  • Fregoso Fernandez Esteban Gabriel, Ph.D. Student
  • Amy Xia Yi Yong, Ph.D. Student
  • Susan Boerner, Unit Technician
  • Miki Otsuki, Technician
  • Masahiro Osada, Unit Intern (from July to October)
  • Yuto Akimoto, Unit Intern (from October to March)
  • Paolo Vincenzo Fioretti, Unit Intern (from February to April)
  • Akiko Guzman, Research Unit Administrator

2. Collaborations

2.1 Local axonal and synaptic maintenance mechanisms in a Drosophila model of Wallerian degeneration

  • Type of collaboration: Joint research
  • Researchers:
    • Assistant Professor Lukas Neukomm, University of Lausanne, Switzerland
    • Maria Paglione, Ph.D. student

2.2 Using nanographene compounds for imaging in neurons

  • Type of collaboration: Joint research
  • Researcher:
    • Assistant Professor Akimitsu Narita, OIST

 

3. Activities and Findings

Neurons need to tightly regulate the flux of information from the periphery to the center and transport defects of signaling complexes, including endosomes, mitochondria and mRNP granules. Some of this perypheral signalling is also generated by axonal local protein synthesis. We have two main lines of research, which deal with the contribution of molecular motors and local translation to axonal homestasis and signalling and reseraching the mechanisms of pathogenesis of ALS.

  1. Axonal transport and translation. We published how genetic depletion of Dynlrb1, a small subunit of the Dynein complex is critical for neuronal survival (Terenzio et al, 2020). In 2023, Emad El-Agamy Abdelaal was able to graduate and publish her work regarding the followup study to the previously mentioned one. In her work, Sara performed a proteomic screening for interactors and characterized the FMRP protein as a Dynein binding partner. Genetic depletion of Dynlrb1 causes FMRP granules accumulation and a decrease clearance of FMRP positive granules. Accumulated FMRP traps FMRP-associated mRNAs and inhibits their translation, with potential fucntional consequences.  Maria Fransiska Emily used customs microfluidics chambers (MFCs), which she designed (Emily et al, 2022) to study axonal transkation. She characterized bulk axonal translation and retrograde transport of translated proteins using both puromycin and transfection with GFP mRNA. She is now taking a sequencing and proteomic approach to study differences in axonal translation between young adult and late adult mice.

 

  1. Mechanisms of axonal pathology in neurodegenerative diseases. We have acquired a collection of human inducible pluripotent stem cells (hiPSCs) from control individuals and Amyotrophic Lateral Sclerosis (ALS) patients. Using this system, Sandra De La Fuente Ruiz at biomarkers of ALS secreted in the culture medium by proteomic analysis.  She is also investigatin mitochondrial activity in ALS. Laurent Guillaud is looking at the role of ATP and mitochondrial activity in the fluidity of the axonal cytosol, with a focus on parkinsonian and ALS models. He found that lower concentration of ATP enhance the condensation of neuronal cytoplasm, with possible ripercussions for the disease.

 

4. Publications

4.1 Journals

  1. FMRP long-range transport and degradation are mediated by Dynlrb1 in sensory neurons. El-Agamy SE, Guillaud L, Kono K, Wu Y, Terenzio M. Mol Cell Proteomics. 2023 Sep 20;22(11):100653. doi: 10.1016/j.mcpro.2023.100653. PMID: 37739344
  2. Mechanisms of axonal degeneration and regeneration of the nervous system. Otsuki M, Terenzio M. Neurosci Res. 2023 Oct 14:S0168-0102(23)00193-1. doi: 10.1016/j.neures.2023.10.003. PMID: 37839523
  3. Intrinsic Burst-Blinking Nanographenes for Super-Resolution Bioimaging.  Zhu X, Chen Q, Zhao H, Yang Q, Goudappagouda, Gelléri M, Ritz S, Ng D, Koynov K, Parekh SH, Chetty VK, Thakur BK, Cremer C, Landfester K, Müllen K, Terenzio M, Bonn M, Narita A, Liu X. J Am Chem Soc. 2024 Jan 26. doi: 10.1021/jacs.3c11152. PMID: 38275287

4.2 Books and other one-time publications

  1. Roles of mRNA Axonal Localization and Translation in Neurodegenerative Diseases. Le Coz M, Zakhia S, Terenzio M. Book chapter in the book Wiring the Nervous System: Mechanisms of Axonal and Dendritic Remodelling in Health and Disease, River Publishers, eBook ISBN 9781032632698, 2024.

4.3 Oral and Poster Presentations

Scientific Talks

  1. “FMRP axonal retrograde transport is critical for its clearance and regulation of translational activity” by Marco Terenzio. KGRI Lecture Series: Seminar on ALS, 2023-05-30. Department of Physiology, School of Medicine, Keio University, Tokyo, Japan.
  2. “FMRP long-range transport and degradation are mediated by Dynlrb1 in sensory neurons”, By Marco Terenzio. 2023-08-04. The 46th annual meeting of the Japan Neuroscience Society. Sendai, Japan.
  3. “Regulation of axonal translation in neuronal survival and regeneration” by Marco Terenzio. 2024-01-21. OIST-JST joint meeting. OIST, Japan.
  4. “Regulation of RNP granule dynamics and axonal translation in sensory and motor neurons” by Marco Terenzio. OIST-RIKEN meeting. 2023-11-17. OIST, Japan.
  5. “Investigating axonal molecular dynamics in regeneration and neurodegenerative diseases” by Marco Terenzio. 2024-02-27. Center for Integrative Biology, University of Trento, Trento, Italy.
  6. “Regulation of RNP granule dynamics and axonal translation in sensory and motor neurons” by Marco Terenzio. 2024-03-01. NICO, University of Torino, Torino, Italy.

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report

6. Meetings and Events

  • Seminar: "A novel function of the nuclear transport factor importin α as a direct DNA-binding protein". 2023-10-24. Speaker: Dr. Kazuya Jibiki, Department of Life Science College of Humanities and Science, Nihon University
  • Seminar: “Axonal transport disfunctions in neurodegenerative diseases”. 2024-03-21. Speaker: Prof. Giampietro Schiavo, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.

7. Other

7.1 Teaching

  • Title: Neuronal Molecular Signaling
  • Curriculum: Course A361 by Prof. Marco Terenzio.
  • Date: Term 3 2023
  • Venue: OIST campus.
  • Lecturer: Marco Terenzio