This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 846282
Project Number: 846282
Project Acronym: MOVEMeNt
Project title: Decoding alpha motor neurons diversity and selective vulnerability to disease
Starting date: 01/02/2020
Duration in months: 24
Call identifier: H2020-MSCA-IF-2018
Free keywords: neuronal diversity, vulnerability, FF-MN, adult, spinal cord, remodeling, neurotoxin, single cell, ALS, SBMA
Abstract: Alpha motor neurons (aMN) are a clinically relevant neuronal population that selectively degenerates in neuromuscular diseases, including amyotrophic lateral sclerosis (ALS) and spinal bulbar muscular atrophy (SBMA). Distinct classes of aMNs (SFR, FFR and FF) degenerate at different rate in these diseases, with the fast fatigable (FF) MNs degenerating first. The molecular mechanisms underlying this selective vulnerability are only partially known. Understanding the molecular logics that shape the identity and function of aMN subtypes in vivo is directly relevant to the development of novel therapeutic strategies. Here I propose to harmonically integrate my solid background in dissecting the molecular fingerprints of distinct neuronal subtypes in adult mice by undertaking new technologies I pioneered at Harvard University, with new skills and knowledge I will build at the Host Institution, which will be critical for the successful achievement of my goal. The overreaching goal of MOVEMeNt is to identify the molecular substrate of disease vulnerability in aMNs. I will (Aim 1) isolate and FACS-purify aMN-nuclei from adult mouse spinal cords, based on the specific expression of aMN markers. Single cell transcriptomic analysis will reveal class-specific molecular fingerprints, including factors playing key roles in suptype-specific development, function, and disease vulnerability. I will also (Aim2) analyze the transcriptional changes of differentially vulnerable aMN classes upon retrograde labeling and functional denervation by neurotoxin intoxication. This work will return candidate genes directly controlling terminal sprouting and remodeling, critical steps that disease-resistant aMN subtypes normally undertake for neuronal loss compensation upon insult. More broadly, I aim to contribute in filling an important knowledge gap by generating the first transcriptomic roadmap of aMN subtypes, and pinpointing at new candidates for therapy development.
Marie Curie IF Fellow: Dr. Emanuela Zuccaro
Presentation: Emanuela Zuccaro obtained her PhD in Neuroscience, Nanotechnology, Robotics and Drug Discovery from the University of Genova in 2012. She spent her PhD training at the iit of Genova and then moved to Harvard University as Postdoctoral Fellow, were she focused her research on cortical development and neural diversity in vivo and in vitro. In 2018 and 2019 she has been awarded the Umberto Veronesi Foundation Postdoctoral Fellowships (CV.pdf).
Emanuela in her MSCA project “MOVEMeNT” – at the Department of Biomedical Sciences under the supervision of Prof. Maria Pennuto - aims at deciphering the motor neuron diversity in the mouse spinal cord to ultimately underpin the molecular logics responsible for their eclectic remodelling capacity and disease vulnerability.
Her research focuses on understanding the molecular mechanisms that govern the establishment of neuronal diversity in the mammalian central nervous system and its impairment during neurodegenerative diseases, such as amyotrophic lateral sclerosis and spinal and bulbar muscular atrophy. In particular, she is interested in decoding what are the molecular mechanisms underlying the selective vulnerability of specific motor neuron classes in neurodegenerative diseases.
