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ANDREA BURGO

dernière mise à jour : 17/09/2015

Statut :

Maître de conférences

Fonction :

Enseignant-Chercheur
Photo de Andrea Burgo

Présentation générale

Présentation

Understanding the molecular bases of the axonopathy in HSP

 

Compelling evidences suggest that defective axon trafficking may be a common mechanism to several neurodegenerative diseases including Hereditary Spastic Paraplegias (HSPs). HSPs are clinically and genetically heterogeneous diseases characterized by a degeneration of corticospinal tract axons, which leads to a bilateral, symmetrical, slowly-progressive spasticity and weakness of the lower extremities. Mutations in the SPG4 gene, encoding spastin, account for approximately 40% of the familial and 6-15% of the sporadic cases with autosomal dominant HSP. Spastin is a member of the AAA ATPase protein family which severs microtubules through an ATP-dependent mechanism. This suggests spastin specific role in the regulation of microtubule dynamics and indeed in related membrane traffic. Interestingly recent results revealed that microtubule-targeting drugs at nanomolar concentrations prevent axonal swelling, the prominent axonal abnormality observed, in SPG4-deficient mice and SPG4 affected patients.

Spastin also interacts with different molecular partners. These interactions partially explain the implication of spastin in cellular functions such as cytokinesis, ER shaping and endosomal traffic. We recently carried out a two-hybrid screen to identify potential new molecular partners of spastin. The preliminary results are interesting and they might clarify the known cellular functions of spastin but also unravel yet unknown functions for spastin.

 

The aims of our research are:

i) to obtain a qualitative and quantitative view on the role of spastin in the regulation of microtubule dynamics and intracellular axonal trafficking, two parameters that notably participate to axon growth and maintenance and are likely linked to axonal swelling;

ii) to decipher the mechanism of axonal swelling rescue by microtubule-targeting drugs;

iii) to characterize the interaction and the role of the new molecular partners of spastin identified by two-hybrid screen.

 

To achieve these goals, we will use different and complementary cellular models to approach, at best, the condition that neurons experience in the SPG4-linked HSP context and to obtain an integrative view on the pathophysiological mechanisms leading to spastin-related HSP based. We use neuronal culture from SPG4-KO mice and cortical neurons derived from human SPG4-mutated iPSCs.

 

 To date no preventive or curative treatments are available to improve spasticity of HSP patients. Obtaining such information might help to progress toward the treatment of this disease and maybe other neurodegenerative pathologies.

 

Methods:

Cell line culture; primary neuronal culture; iPSCs; live cell video imaging; immunofluorescence; post-acquisition image processing and analysis; molecular biology; biochemistry.

 

Collaboration:

I-STEM (Genopole), Evry, France

Brain and Spine Institut (ICM), Paris, France

 

 

Laboratoire

Publications

Publications

2013
  • Burgo A. *, Casano A. *, Kuster A. *, Arold S.T., Wang G., Nola S., Verraes A., Dingli F., Loew D., and Galli T. Increased activity of the v-SNARE TI-VAMP/VAMP7 by tyrosine phosphorylation in the Longin domain.  Journal of Biological Chemistry, Epub ahead of print. * These authors contributed equally to this work.
2012
  • Burgo A., Formstecher E., Galli T. Molecular network for the transport of intracellular vesicles from cell center to periphery.  Med Sci (Paris) 28(12):1040-1.
  • Burgo A., Proux-Gillardeaux V., Sotirakis E., Bun P., Casano A., Verraes A., Liem R.H., Formstecher E., Coppey M., and Galli T. A molecular network for the transport of the TI-VAMP/VAMP7 vesicles from cell center to periphery.  Developmental Cell 23(1), 166-80.
  • Danglot L., Freret T, Le-Roux N., Narboux-Nême N., Burgo A., Hyenne V., Contremoulins V., Dauphin J., Bizot J.C., Vodjdani G., Gaspar P., Boulouard M., Poncer J.C., Galli T. and Simmler M.C. Vezatin is essential for dendritic spine morphogenesis and functional synaptic maturation. Journal of Neuroscience  32(26), 9007-22.
  • Zylbersztejn K., Petkovic M., Burgo A., Deck M., Garel S., Marcos S., Bloch-Gallego E., Nothias F., Serini G., Bagnard D., Binz T. and Galli T. The vesicular SNARE Synaptobrevin is required for Semaphorin 3A axonal repulsion.  Journal Cell Biology 196, 37-46.
2009

 

  • Burgo A.*, Sotirakis E.*, Simmler M.C., Verraes A., Chamot C., Simpson J.C., Lanzetti L., Proux-Gillardeaux V. and Galli T. Role of Varp, a Rab21 exchange factor and TI-VAMP/ VAMP7 partner, in neurite growth.  Embo Reports 10, 1117-24. * These authors contributed equally to this work.

 

  • Burgo A.*, Tsaneva-Atanasova K.*, Galli T. and Holcman.  Quantifying neurite growth mediated by interactions between secretory vesicles, microtubules and actin networks. Biophysical Journal 96(3), 840-857. * These authors contributed equally to this work.
2006
  • Zatti G., Burgo A., Giacomello M., Barbiero L., Guidoni R., Sinigaglia G., Florean C., Nacmias B., Binetti G., Sorbi S., Pizzo P and Fasolato C. Presenilin mutations linked to Familial Alzheimer’s Disease reduce endoplasmic reticulum and Golgi apparatus calcium levels. Cell Calcium 39, 539-550.
  • Facchinetti F., Fasolato C.(equal contributor), Del Giudice E., Burgo A., Furegato S., Fusco M.,  Basso E., Seraglia R., D’Arrigo  and  Leon A. Nimodipine selectively stimulates -amyloid 1-42 secretion by a mechanism independent of calcium influx blockage. Neurobiology of Aging 27, 218-227.
2003
  • Burgo A., Carmignoto G., Pizzo P., Pozzan T. and Fasolato C. Paradoxical Ca2+ rises induced by low external Ca2+ in rat hippocampal neurones. Journal of Physiology 549, 537-552.
2001
  • Pizzo P., Burgo A., Pozzan T. and Fasolato C. Role of capacitative calcium entry on glutamate-induced calcium influx in type-I rat cortical astrocytes. Journal of Neurochemistry 79, 98-109.
1999
  • Bittner C., Burgo A., Murphy P. J., Sung C. H. and Thornhill A.J.  A Synthetic Approach to the Plakortones. Tetrahedron Letters 40, 3455-3456.

Enseignements

Enseignements

  •  Travaux dirigés et travaux pratiques dans les cours de biologie cellulaire B11, Licence 1 et de biochimie métabolique B32, Licence 2.
  • Coordinateur de la formation continue pour le département de Biologie Cellulaire UEVE.

Curriculum vitae

Formations

  • 2000-2004 Doctorat de recherche en Biologie et Pathologie Moléculaire et Cellulaire, Département de Science Biomédical Expérimentales, Université de Padoue, Italie.
  • 1993-1999 Maitrise en Chimie et Technologies Pharmaceutiques avec la mention, de 109 sur 110, Faculté de Pharmacie, Université de Padoue, Italie.
  • 1985-1990 Diplôma de Chimie Industriel, Institut technique “G.Natta”, Padoue, Italie.

 

 

 

Parcours professionnel

  • Février 2006-Février 2012  

Chercheur dans l’équipe de Dr. Thierri Galli, Membrane Traffic in Neuronal and Epithelial Morphogenesi, Institut Jacques Monod, Université Paris Diderot, Paris, France.

  • Mars 2004-Janvier 2006

Chercheur dans l’équipe de Prof. Tullio Pozzan, Département Science Biomédical Expérimentales,

  • Novembre 2000-Janvier 2004

Doctorant en Biologie et Pathologie Moléculaire et Cellulaire, Département de Science Biomédical Expérimentales, Université de Padoue, Italie. Titre de la thèse: “Dynamics of intra- and extra- cellular calcium in rat cortical neurones and astrocytes”. Directeur de laboratoire : Prof. Tullio Pozzan, DHR: Dr.ssa Cristina Fasolato.

  • Décembre 1998-Décembre 1999

DEA dans l’équipe de Prof. Tullio Pozzan, Département Science Biomédical Expérimentales, Faculté de Biologie, Université de Padoue, Italie. Encadrant: Dr. Cristina Fasolato et Paola Pizzo.

  • Mai-Août 1998

Stage expérimental  réalisé dans le cadre de programme ERASMUS  (European community Action Scheme for the Mobilility of University Students) dans l’équipe de Prof. P.J. Murphy, Département de Chimie, Université de Bangor, Pays de Galles, Angleterre. 
 

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