Non-Coding RNA Explosion: Novel Implications in Neurotrophin Biology
FIRB, MIUR-Cineca

Summary

The main focus of the project is the identification of non-coding RNAs (ncRNA) that regulate the expression of Neurotrophins (NT) and NT receptors (NTR). ncRNAs are a novel class of regulatory molecules that have been shown to be involved in almost all biological phenomena, including development and physiology of the nervous system.
Neurotrophins (NT) (BDNF, NGF and NT sensu stricto) are growth factors that control development, differentiation, synaptic plasticity and survival of several types of neuronal and glial cells in the embryonic and adult central nervous system and sensory organs. Based on the NT role in development and physiology of the nervous system, the present project aims at extending our knowledge on NTs molecular pathways, with emphasis on the their relationships with stress, aging and diseases.
The project will take advantage of as bioinformatic, molecular, genetic, biochemical and behavioural multidisciplinary approaches, with the aim to acquire new insights on the genetic regulatory networks and on the functions exerted by NT and NT receptors during the correct development and in conditions of thermal, social and nutritional stress. A distinctive feature of this research proposal is the use of three different model systems: cells, mouse and zebrafish.
In summary, the main purpose of the present project is to study the molecular, cellular and behavioural phenotype of NTs and NTRs, with emphasis on the relationships of these molecules with stress, ncRNAs and neurodegenerative diseases (NDs).
We are knocking out the BDNF, one of the most known neurotrophin together NGF, in zebrafish using the CRISPR/Cas9 thecnology to he improve our understanding of the role played by NTs during embryonic development and adult brain physiology, with particular attention to the biomedical impact in terms of diagnosis and treatment of neurodegenerative diseases.

What we do

We built a national network, in which the Stazione Zoologica Anton Dohrn of Napoli is the leader Institute, with the aim to merge multidisciplinary approaches and competences to reveal the importance of NT during vertebrate’s brain development.

Partners

Stazione Zoologica Anton Dohrn, Napoli (Unit 1); Dipartimento di Biologia e Biotecnologie "Charles Darwin", Università di Roma Sapienza (Unit 2); Dipartimento di Scienze Biologiche, Università di Napoli Federico II (Unit 3); Laboratorio di Bioinformatica, Università del Sannio (Unit 4).

Research Area

Organismal Biology

Project Lifetime

21 March 2013 to 20 March 2018

SZN Role

Coordinator of the whole project and Research Unit 1

Principal Investigator

Salvatore D’Aniello

Funding Institution

Futuro In Ricerca (FIRB), http://futuroinricerca.miur.it; Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR), http://www.istruzione.it        
Grant no. RBFR12QW4I

Contribution to SZN

€369.443 (MIUR contribution)

Publications

D’Agostino Y, Locascio A, Ristoratore F, Sordino P, Spagnuolo A, Borra M* and D’Aniello S* (2015). A rapid and cheap methodology for CRISPR/Cas9 zebrafish mutant screening. Molecular Biotechnology, in press.

Meet the team

Salvatore D’Aniello, Ricercatore
Ylenia D’Agostino, PhD student
Annamaria Locascio, Ricercatore
Filomena Ristoratore, Ricercatore
Paolo Sordino, Ricercatore
Antonietta Spagnuolo, primo Ricercatore

Summary

The DIsCO project, Diatom life cycles, molecular controls and contribution to ecosystem dynamics, is part of the Marine Microbial Initiative promoted by the Gordon and Betty Moore Foundation.
In this highly multidisciplinary project, laboratory approaches, studies at sea and modelling approaches are combined to answer various questions related to the life cycle of the diatom Pseudo-nitzschia multistriata. In particular we aim to i) understand the endogenous mechanisms that control the diatom life cycle (what are the signal transduction mechanisms? What are the gene networks involved? Is there an epigenetic control in the transitions between the life cycle phases?); ii) follow the natural populations at sea through population genomics, in order to understand the genetic structure but also the dynamics of genome evolution; iii) estimate how much the genetic diversification processes are guided by environmental factors, how much genetic diversity is the result of the neutral interaction between cell division, genetic mutation and recombination, and what is the expected effect of environmental perturbations on rates of division, mutation and recombination.
The project foresees the development and application of technologies that are innovative for phytoplankton, including the ATAC-seq method for epigenetic studies, the CRISPR/Cas9 technology for the study of gene function, and single-cell transcriptomics for the analysis of the different sexual stages.
The possibility of formulating hypotheses in the laboratory and verifying them with data obtained at sea, and vice versa, and the synthesis envisaged through modelling give this project a highly innovative connotation.
Projects outputs will be an increased knowledge on the microscopic component of marine ecosystems, improved understanding of genome evolution dynamics and of the evolutionary consequences of the process of sexual reproduction in a marine unicellular organism.

What we do

The SZN is involved in all project activities. To address the different questions, part of the study is carried out by laboratory experimentation with advanced functional genomics techniques, part involves sampling at the the long-term LTER-MareChiara series site in the Gulf of Naples and in other Mediterranean sites, and a third part involves the application of modeling approaches. High-throughput sequencing methods and advanced bioinformatics analyses are applied for different aspects of the project.

Partners

Stazione Zoologica Anton Dohrn, Napoli, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste.

Research Area

Functional Genomics, Genome Evolution, Population genetics, Modelling

Project Lifetime

December 2018 - November 2021

SZN Role

Coordinator

Principal Investigator

Mariella Ferrante

Project Leader

Mariella Ferrante

Funding Institution

The Marine Microbiology Initiative funded by the Gordon and Betty Moore Foundation (USA)

Dedicated website

Under construction

Personnel involved

Mariella Ferrante, Principal investigator

Marina Montresor, Senior Researcher
Daniele Iudicone, Senior Researcher
Domenico D’Alelio, Researcher
Rossella Annunziata, Researcher
Francesco Manfellotto, Post-doc
Pina Marotta, Post-doc
Maria Valeria Ruggiero, Post-doc
Monia Teresa Russo, Technician
Pasquale De Luca, Senior Technologist
Elio Biffali, Senior Technologist
Gabriele Procaccini, Research Director

Empowering an integrated platform for the study of human diseases with great impact by means of system phenotyping of model animals: mouse and zebrafish clinic (MouZeCLINIC).

Summary

MouZeCLINIC is an infrastructural and training network in biomedicine by means of acquatic and terrestrial model organisms. Through the use of advanced methods of genetic analysis and imaging technologies, MouZeCLINIC aims at performing system phenotyping in zebrafish and mouse models of human diseases. MouZeCLINIC is training a new generation of young researchers by combining the strengths of modern technologies with a real understanding of traditional approaches. The MouZeCLINIC consortium involves two research centers and one academic institution that will provide the MouZeCLINIC fellows with expertise, specialized equipment and training on a wide range of approaches and methodologies incorporated in developmental genetics and translational medicine.

What we do

We are one of the three partners and are contributing by training students, by developing a zebrafish infrastructure and by studying fish models of neuroinflammation, toxicity and metabolism.

Partners

BioGem scarl – Ariano Irpino (Avellino) - IT; Stazione Zoologica Anton Dohrn, Napoli – IT; Università della Magna Graecia – Germaneto (Catanzaro) - IT

Research Area

Organismal Biology

Project Lifetime

January 2012 to July 2015

SZN Role

Partner

Principal Investigator

Paolo Sordino

Funding Institution

Ministero dell’Istruzione dell’Università e della Ricerca (MIUR):
Programma Operativo Nazionale - ”Ricerca e Competitività” 2007-2013
Grant no. PONa3_00239

Contribution to SZN

Infrastructure € 1.273.424,00 (MIUR contribution)
Training € 733.670,00 (MIUR contribution)

Dedicated website

http://www.ponrec.it/open-data/risultati/potenziamento-strutturale/pona3_00239

Publications

Pappalardo A, Porreca I, Caputi L, De Felice E, Schulte-Merker S, Zannini M, Sordino P (in press) Thyroid development in zebrafish lacking TAZ. Mechanisms of Development.

Fortunato AE, Sordino P, Andreakis N (in press) Evolution of the SOUL heme-binding protein superfamily across Eukarya. J Molecular Evolution.

Porreca I, D’Angelo F, Gentilcore D, Carchia E, Amoresano A, Affuso A, Ceccarelli M, De Luca P, Esposito L, Guadagno FM, Mallardo M, Nardone A, Maccarone S, Pane F, Scarfò M, Sordino P, De Felice M, Ambrosino C (2014) Cross-species toxicogenomic analyses and phenotypic anchoring in response to groundwater low-level pollution. BMC Genomics 15: 1067.

De Felice E, Porreca I, Alleva E, De Girolamo P, Ciriaco E, Germanà A, Sordino P (2014) Localization of BDNF expression in the developing brain of zebrafish. Journal of Anatomy 224: 564.

Ferriero R, Manco G, Lamantea E, Nusco E, Ferrante MI, Sordino P, Stacpoole PW, Lee B, Zeviani M, Brunetti-Pierri N (2013) Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis. Science Transl Med, 5 (175): 175ra31.

Porreca I, De Felice E, Fagman H, Di Lauro R, Sordino P (2012) Zebrafish bcl2l is a survival factor in thyroid development. Developmental Biology 366:142.

Meet the team

Paolo Sordino, ricercatore