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Laboratory of Neurobiology and Molecular Genetics

P.I: Prof. Ferdinando Fiumara, MD, PhD

Staff

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Activity

Our lab is currently developing two main lines of research.

Memory-related synaptic plasticity

One research line focuses on the molecular mechanisms of different forms of short- and long-term synaptic plasticity underlying learning and memory. We are interested in the processes by which neurons can vary neurotransmitter release at their synapses over both short- and long-term time scales. We invesigate these mechanisms through a combination of molecular, biochemical, electrophysiological, and imaging approaches. In particular, we focus on post-translational modifications of synapsins, a family of synaptic phosphoproteins, in the modulation of evoked neurotransmitter release and short-term homoynaptic plasticity. Furthermore, we are interested in the molecular mechanisms underlying the long-term maintenance of synaptic plasticity through self-sustaining dynamics of translational and non-translational regulation involving micro-RNAs and the synaptic proteome.

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Neurological and muscular genetic diseases

A parallel research line concerns the structural, molecular and cellular mechanisms of genetic diseases characterized by polyglutamine (polyQ) or polyalanine (polyA) expansions in proteins, such as Huntington's disease (HD), cleidocranial dysplasia (CCD) and oculopharyngeal muscular dystrophy (OPMD). Furthermore, we are investigating fundamental physiopathological mechanisms underlying the molecular pathogenesis of Rett syndrome (RTT), a neurodevelopmental disorder, focusing on a group of mutations affecting the MECP2 gene. This research integrates bioinformatics, evolutionary, structural, molecular, and cell biological analyses through a multidisciplinary approach that is essential to unravel the complexity of these genetic diseases.

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Funding agencies

Our work has also been funded by:

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ERC Sectors:

LS2_10 - Bioinformatics

LS2_6 - Molecular genetics, reverse genetics and RNAi

LS5_11 - Neurological disorders (e.g. Alzheimer's disease, Huntington's disease, Parkinson's disease)

LS5_2 - Molecular and cellular neuroscience

 

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Publications

Select publications:

Marchetti C, Vaglietti S, Rizzo F, Di Nardo G, Colnaghi L, Ghirardi M, Fiumara F. (2022) Heptad stereotypy, S/Q layering, and remote origin of the SARS-CoV-2 fusion core. Virus evolution 7(2) veab097 [DOI  PMID]

Vaglietti S, Fiumara F. (2021) PolyQ length co-evolution in neural proteins. NAR genomics and bioinformatics 3(2) lqab032 [DOI  PMID]

Pelassa I, Cibelli M, Villeri V, Lilliu E, Vaglietti S, Olocco F, Ghirardi M, Montarolo PG, Cora D, Fiumara F. (2019) Compound Dynamics and Combinatorial Patterns of Amino Acid Repeats Encode a System of Evolutionary and Developmental Markers. Genome biology and evolution 11(11) 3159-3178 [DOI  PMID]

Lilliu E, Villeri V, Pelassa I, Cesano F, Scarano D, Fiumara F. (2018) Polyserine repeats promote coiled coil-mediated fibril formation and length-dependent protein aggregation. Journal of structural biology 204(3) 572-584 [DOI  PMID]

Fiumara F, Rajasethupathy P, Antonov I, Kosmidis S, Sossin WS, Kandel ER. (2015) MicroRNA-22 Gates Long-Term Heterosynaptic Plasticity in Aplysia through Presynaptic Regulation of CPEB and Downstream Targets. Cell reports 11(12) 1866-75 [DOI  PMID]

Pelassa I, Fiumara F. (2015) Differential Occurrence of Interactions and Interaction Domains in Proteins Containing Homopolymeric Amino Acid Repeats. Frontiers in genetics 6 345 [DOI  PMID]

Pelassa I, Cora D, Cesano F, Monje FJ, Montarolo PG, Fiumara F. (2014) Association of polyalanine and polyglutamine coiled coils mediates expansion disease-related protein aggregation and dysfunction. Human molecular genetics 23(13) 3402-20 [DOI  PMID]

Fiumara F, Fioriti L, Kandel ER, Hendrickson WA. (2010) Essential role of coiled coils for aggregation and activity of Q/N-rich prions and PolyQ proteins. Cell 143(7) 1121-35 [DOI  PMID]

Giachello CN, Fiumara F, Giacomini C, Corradi A, Milanese C, Ghirardi M, Benfenati F, Montarolo PG. (2010) MAPK/Erk-dependent phosphorylation of synapsin mediates formation of functional synapses and short-term homosynaptic plasticity. Journal of cell science 123(Pt 6) 881-93 [DOI  PMID]

Rajasethupathy P, Fiumara F, Sheridan R, Betel D, Puthanveettil SV, Russo JJ, Sander C, Tuschl T, Kandel E. (2009) Characterization of small RNAs in Aplysia reveals a role for miR-124 in constraining synaptic plasticity through CREB. Neuron 63(6) 803-17 [DOI  PMID]

Massobrio P, Tedesco M, Giachello C, Ghirardi M, Fiumara F, Martinoia S. (2009) Helix neuronal ensembles with controlled cell type composition and placement develop functional polysynaptic circuits on Micro-Electrode Arrays. Neuroscience letters 467(2) 121-6 [DOI  PMID]

Fiumara F, Milanese C, Corradi A, Giovedi S, Leitinger G, Menegon A, Montarolo PG, Benfenati F, Ghirardi M. (2007) Phosphorylation of synapsin domain A is required for post-tetanic potentiation. Journal of cell science 120(Pt 18) 3228-37 [DOI  PMID]

Fiumara F, Leitinger G, Milanese C, Montarolo PG, Ghirardi M. (2005) In vitro formation and activity-dependent plasticity of synapses between Helix neurons involved in the neural control of feeding and withdrawal behaviors. Neuroscience 134(4) 1133-51 [DOI  PMID]

Claverol-Tinture E, Ghirardi M, Fiumara F, Rosell X, Cabestany J. (2005) Multielectrode arrays with elastomeric microstructured overlays for extracellular recordings from patterned neurons. Journal of neural engineering 2(2) L1-7 [DOI  PMID]

Fiumara F, Giovedi S, Menegon A, Milanese C, Merlo D, Montarolo PG, Valtorta F, Benfenati F, Ghirardi M. (2004) Phosphorylation by cAMP-dependent protein kinase is essential for synapsin-induced enhancement of neurotransmitter release in invertebrate neurons. Journal of cell science 117(Pt 21) 5145-54 [DOI  PMID]

Ghirardi M, Benfenati F, Giovedi S, Fiumara F, Milanese C, Montarolo PG. (2004) Inhibition of neurotransmitter release by a nonphysiological target requires protein synthesis and involves cAMP-dependent and mitogen-activated protein kinases. The Journal of neuroscience : the official journal of the Society for Neuroscience 24(21) 5054-62 [DOI  PMID]

Casadio A, Fiumara F, Sonetti D, Montarolo PG, Ghirardi M. (2004) Distribution of sensorin immunoreactivity in the central nervous system of Helix pomatia: functional aspects. Journal of neuroscience research 75(1) 32-43 [DOI  PMID]

Fiumara F, Onofri F, Benfenati F, Montarolo PG, Ghirardi M. (2001) Intracellular injection of synapsin I induces neurotransmitter release in C1 neurons of Helix pomatia contacting a wrong target. Neuroscience 104(1) 271-80 [DOI  PMID]

 

Last update: 09/05/2022 11:03
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