Laboratory of neuro-epigenetics

The main interest of our laboratory is to unravel the molecular machinery regulating the epigenome of neuronal cells. In particular, characterizing the histone code responsible for the REST/NRSF-mediated neuronal gene repression, we identified the first chromatin-associated flavo-protein, the histone demethylase Lysine-Specific Demethylase 1, LSD1. In collaboration with the laboratory of Andrea Mattevi, we addressed several functional properties of this demethylase. We showed that LSD1 can read the histone code thanks to a specific mechanism of histone recognition and analyzed the three-dimensional structure unraveling the structural bases of this feature.

 

Recently we identified a neuronal splicing isoform of LSD1, neuroLSD1, an exceptional example of epigenetic enzyme specifically devoted to neurons and exclusively present in mammals. Remarkably, this isoform can modulate its own activity in response to specific signals, providing a molecular link between epigenetic language and neuronal plasticity. This discovery set the basis of the two main projects currently being pursued in our laboratory.

 

Main research lines

-One project plans to answer how alternative splicing enhance LSD1 tuneability and what is the contribution of LSD1 isoforms in the acquisition and maintenance of neuronal phenotype in mammals. Using chromatin biochemistry, molecular biology and mouse genetics we are analyzing the role of neuroLSD1 in neuronal functions: the molecular features of epigenetic regulation by neuroLSD1, determining its effect on chromatin structure and gene transcription and its specific targets; the nature of the neuronal signals able to modulate epigenetic activity by phosphorylation. Moreover, to gain a deeper understanding of the neuronal processes in which LSD1 is involved, we are characterizing the phenotype of a neuroLSD1 null mouse mutant at the level of chromatin, cells, neuronal connections and behavior.

-The second research project aims to investigate the role of neuroLSD1 in neuronal disorders.

Indeed, we found that in the brain, a correct ratio between LSD1 and neuroLSD1 contributes to the regulation of excitability and when altered, could represent a pathogenic event associated to neurological and neuropsychiatric disorders.

 

Grants

• Progetto Bandiera CNR-EPIGEN 2012-1015 (http://www.epigen.it/participants)
  Title “Epigenetic mechanism of plasticity and neuronal maturation.
  Role in the project: Principal Investigator e coordinatore di un progetto multicentrico.

• CARIPLO 2009-2012 Title: “A multilevel approach to study neuronal and synaptic development: two processes impaired in mental retardation.”
  Role in the project: Principal Investigator e coordinator of a multicentric project

• PRIN 2009-2011 Title: “Alternative splicing and epigenetic drugs to interfere with the activity of the histone demethylase LSD1 in vivo”.
  Role in the project: Unit coordinator

• PRIN 2004-2006 Title: “Enzyme complexes action on biogenic amines involved in neurotrasmitter matabolism and chromatin remodeling”.
  Role in the project: Unit coordinator

• PRIN 2006-2008. Title: “Structural properties and functional activities in a chromatin remodeling nuclear complex”.
  Role in the project: Unit coordinator

• PUR2009 Title “Ruolo dello splicing nel regolare l'attività epigenetica di Lysine Specific Demethylase 1, LSD1, nel sistema nervoso.”
  Role in the project: Principal Investigator

• ELETHON Grant numero GGP07078, 2007-2009. Title: “Dissecting the epigenetic features at the basis of facioscapolohumeral dystrophy (FSHD)”.
  Role in the project: Unit coordinator

• MINISTERO DEGLI ESTERI (MAE), JOINT MOBILITY PROJECTS FOR THE EXCHANGE OF RESEARCHERS 2008-2010 Title “Characterization of the epigenetic mechanism modulated by the histone demethylase LSD1 in the nervous system”.
  Role in the project: Principal Investigator

 

Group composition

The Research Group is composed by Elena Battaglioli (assistant researcher BIO/13), Francesco Rusconi (Biologist, postdoctoral fellow); Emanuela Toffolo (Technician and PhD student). In the laboratory are routinely guested bachelor and master students.

 

Contacts

Elena Battaglioli  (E-mail. Elena.battaglioli@unimi.it)
Skype: elenabattaglioli
Phone: 0250315859 and 0250315844

 

Location

Via Viotti 3/5, 20133 Milan, Italy