Profilo personale

Silvia Mandillo

Le informazioni pubblicate in questa pagina sono gestite in completa autonomia da SILVIA MANDILLO il/la quale se ne assume ogni responsabilità

She graduated in Natural Sciences at Universita' La Sapienza- Roma in 1995 with a thesis in Psychobiology, then she obtained her PhD in Psychology at Tufts University, Medford-Boston, USA in 2001. During Graduate School at Tufts University she worked as Research Assistant and Primate Facility manager in the Psychopharmacology Lab (1996-1998) and Nutrition Lab (1998-2001) of the Psychology Dept. From 2001 to 2002 she was a Postdoctoral fellow at Psychobiology Lab, Dept. of Genetics and Molecular Biology at Universita' La Sapienza Roma.

Since 2003 she is Research Scientist at CNR Institute of Cell Biology (2003-2010), Institute of Cell Biology and Neurobiology (2011-2019), and since 2019 Institute of Biochemistry and Cell Biology. Since 2004 she is faculty at Universita' di Roma La Sapienza, Master in Neurobiology, courses of 'Techniques for the study of animal behavior' and 'Methods in Behavioral Neuroscience'. In 2013 she obtained the Abilitazione Scientifica Nazionale a Professore Associato.

Her research focuses on the study of motor and cognitive functions as well as social and emotional behaviors by using automated systems and ethologically based direct behavioral observations. She is currently conducting in-depth behavioral analysis of inbred and mutant mouse strains to develop genetic models of neurodegenerative and psychiatric diseases, e.g. Parkinson's Disease, Amyotrophic Lateral Sclerosis, Schizophrenia, Autism Spectrum Disorders, anxiety and depression.

Aree di interesse:

Psychobiology, Behavioral Pharmacology, Models of Drug Abuse, Neurodegenerative and Psychiatric Diseases, Learning and Memory, Behavioural Neurobiology, Mouse Phenotyping, Animal Welfare, Statistical analysis.


Contatti

Telefono: +39-06-90091410/205
Pec: silvia.mandillo@postecert.it

Identificatori Internazionali

Scopus Author ID: 6603484229
WoS Researcher ID: E-6503-2019
Research Gate: Silvia_Mandillo
Google Scholar: iuT0jBUAAAAJ&hl=en

H-index

Google Scholar H-Index: 22
ISI-WoS H-Index: 20

Attività

Partecipazione a progetti scientifici, campagne di rilevamento, commesse o moduli/attività/sottoprogetti

EMMAinf - European Mouse Mutant Archive Infrastructure

Ruolo: Partecipante Progetto
Perodo di partecipazione all'attività: 07/2004 - oggi
Organizzazioni coinvolte: CNR ISTITUTO DI BIOLOGIA CELLULARE IN MONTEROTONDO; DE TYPAGE ET D'ARCHIVAGE ANIMAL IN ORLEANS; FRANCE; FRANCE; GERMANY; ILLKIRCH; ITALY (CORE STRUCTURE); PORTUGAL; SPAIN.; SWEDEN; THE CNRS CENTRE DE DISTRIBUTION; THE EMBL EUROPEAN BIOINFORMATICS INSTITUTE IN HINXTON; THE FCG INSTITUTO GULBENKIAN DE CIêNCIA IN OEIRAS; THE GIE-CERBM INSTITUT CLINIQUE DE LA SOURIS; THE HELMHOLTZ ZENTRUM MüNCHEN INSTITUTE OF EXPERIMENTAL GENETICS IN MUNICH; THE KAROLINSKA INSTITUTET IN STOCKHOLM; THE MRC MAMMALIAN GENETICS UNIT IN HARWELL; THE WELLCOME TRUST SANGER INSTITUTE IN HINXTON; UK; UK; UK AND THE CSIC CENTRO NACIONAL DE BIOTECNOLOGíA IN MADRID;

Finalità del progetto: The mouse shows great similarities in development, physiology and biochemistry to humans. This makes it a key model for research into human disease. The identification of all the genes in mice and humans in the Human Genome Project has shown that about 99% of the genes in mice have a homologue in humans. This is important as to date around 5000 human diseases have been shown to be caused by an error in our genetic make-up. In numerous other diseases e.g. in diabetes, errors in our genetic make-up are a contributory factor. The similarity of the mouse and human genome means that genes associated with disease in humans can be investigated in mouse models. This knowledge can then be transferred to understanding and treatment of disease in humans. Therefore, it is imperative that a secure, well managed central repository exists for the cryopreservation and dissemination of mouse lines which will ensure pan- European access and efficient delivery of mouse models, prerequisites for maintaining Europe's leading role in the functional annotation of the mouse genome.
Risultati ottenuti: Results of the behavioral and neurchemical characterization of some mouse model mutants archived in EMMA and relevant for the study of Parkinson's disease, Hungtinton's disease and ALS as well as development of the sensori-motor system have been published in the follwing articles: -Marazziti D, Golini E, Mandillo S, Magrelli A, Witke W, Matteoni R, Tocchini-Valentini G (2004). Altered dopamine signaling and MPTP resistance in mice lacking the Parkinson's disease-associated GPR37/parkin-associated endothelin-like receptor. PNAS 101: 10189-10194. -Marazziti D, Mandillo S, Di Pietro C, Golini E, Matteoni R, Tocchini-Valentini G P (2007) GPR37 associates with the dopamine transporter to modulate dopamine uptake and behavioral responses to dopaminergic drugs. PNAS, 104: 9846-9851. -Marazziti D, Di Pietro C, Mandillo S, Golini E, Matteoni R, Tocchini-Valentini GP (2011). Absence of the GPR37/PAEL receptor impairs striatal Akt and ERK2 phosphorylation, DeltaFosB expression, and conditioned place preference to amphetamine and cocaine. FASEB J. 25(6): 2071-81. -Mandillo S, Golini E, Marazziti D, Di Pietro C, Matteoni R, Tocchini-Valentini GP (2013). Mice lacking the Parkinson's related GPR37/PAEL receptor show non-motor behavioral phenotypes: age and gender effect. Genes Brain Behav.,12(4):465-77. -Marazziti D, Di Pietro C, Golini E, Mandillo S, La Sala G, Matteoni R, Tocchini-Valentini GP (2013). Precocious cerebellum development and improved motor functions in mice lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor. PNAS, 110(41):16486-16491. -Mandillo S*, Heise I*, Garbugino L*, Tocchini-Valentini GP, Giuliani A, Wells S, Nolan PM. Early motor deficits in mouse disease models are reliably uncovered using an automated home cage wheel-running system: a cross-laboratory validation. Disease Models and Mechanisms (under revision). Dissemination of knowledge of most relevant techniques of mouse behavioral phenotyping have been the focus of several courses and training workshops (Corso Tecniche di studio del comportamento, Laurea magistrale in Neurobiologia, Universita' "Sapienza", Roma; Theoretical course "Mouse Behavioral Phenotyping", ICGEB International Centre for Genetic Engineering and Biotechnology, Trieste; Techniques and Approaches in Mouse Behavioural Phenotyping, ICS Institut Clinic de la Souris, Strasbourg) as weel as the main topic of the following published articles: -Brown S. et al. and members of EUMORPHIA consortium. (2005). EMPReSS: standardised phenotype screens for functional annotation of the mouse genome. Nature Genetics, 37 (11): 1155. -Mandillo S, Tucci V, Holter SM, Meziane H, Al Banchaabouchi M, Kallnik M, Lad HV, Nolan PM, Ouagazzal AM, Coghill EL, Gale K, Golini E, Jacquot S, Krezel W, Parker A, Riet F, Schneider I, Marazziti D, Auwerx JH, Brown SD, Chambon P, Rosenthal N, Tocchini-Valentini G, Wurst W (2008) Reliability, Robustness, and Reproducibility in mouse behavioral phenotyping: a cross-laboratory study. Physiological Genomics, 34: 243-255. -Morgan H, Beck T, Blake A, Gates H, Adams N, Debouzy G, Leblanc S, Lengger C, Maier H, Melvin D, Meziane H, Richardson D, Wells S, White J, Wood J; EUMODIC Consortium, de Angelis MH, Brown SD, Hancock JM, Mallon AM (2010). EuroPhenome: a repository for high-throughput mouse phenotyping data. Nucleic Acids Res. 38 (Database issue): D577-85. Epub 2009 Nov 23. Implementation and study of forms of environmental enrichment to improve animal well-being has been the main topic of lectures on 'Arricchimento ambientale e sociale' for the Corso "Scienza degli animali da laboratorio" at Fondazione S. Lucia - European Brain Research Institute (EBRI) CNR, and of the activities of the Animal Welfare Advisory Board of which I am a member.
Attività svolta: Phenotypic analysis of mouse models of human diseases with particular attention to neurodegenerative disease models (Parkinson's disease, Hungtinton's disease, ALS) and disorders of the sensori-motor system. Dissemination of knowledge of most relevant techniques of mouse behavioral phenotyping. Implementation and study of forms of environmental enrichment to improve animal well-being.

COST Action CA20135 -TEATIME "Improving biomedical research by automated behaviour monitoring in the animal home-cage"

Ruolo: Proposer, Management Committee Member, WG Co-Leader, Core Group Member
Perodo di partecipazione all'attività: 10/2021 - oggi
Organizzazioni coinvolte: COST ASSOCIATION;

The aim of this Action is to bring together European organizations developing and using automated home-cage monitoring technologies, combining experts in mouse behaviour, laboratory animal science and data science, to critically and transparently assess the potential of these technologies, to develop user guidelines and standard operating procedures and to identify needs for further technological development, including analysis of big data.

IMPC

Ruolo: Membro
Sito web attività: http://www.mousephenotype.org
Perodo di partecipazione all'attività: 01/2012 - oggi
Organizzazioni coinvolte: EUROPEAN MOLECULAR BIOLOGY LABORATORY (EMBL); GSF FORSCHUNGSZENTRUM FUR UMWELT UND GESUNDHEIT, GMBH; INSTITUT CLINIQUE DE LA SOURIS (ICS); ISTITUTO ITALIANO DI TECNOLOGIA (IIT); MRC MEDICAL RESEARCH COUNCIL;
  • International Mouse Phenotyping Consortium: "Building a truly comprehensive functional catalogue of a mammalian genome". Research Activity In-depth analysis of mouse behavior applied to mutant mouse models of human neurodegenerative and psychiatric diseases (Parkinson's, Huntington's, ALS, anxiety, depression, schizophrenia, autism). Study of motor, emotional and cognitive functions through an ethological approach at various ages from development to ageing. Evaluation of gender differences. Set up, standardisation and validation of tests for the behavioural phenotyping of mouse genetic models. Neurosurgery in small rodents.

Progetto CNR: PI.P02 - Progetto di Interesse-Invecchiamento [Scheda progetto ]

Ruolo: Partecipante Progetto
Perodo di partecipazione all'attività: 2012 - oggi

Sottoprogetto 1-Studio dei meccanismi molecolari della neurodegenerazione e dell'invecchiamento. WP1.8 Modelli transgenici d'invecchiamento cerebrale e di longevità.

PhenoScale: Large-scale, high-throughput automated systems for phenotyping mouse models of human disease

Ruolo: Partecipante Progetto
Perodo di partecipazione all'attività: 03/2009 - 02/2012
Organizzazioni coinvolte: CONSIGLIO NAZIONALE DELLE RICERCHE (CNR); FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA (IIT); GERMANY; GERMANY; HELMOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH (HMGU); ITALY; ITALY; MEDICAL RESEARCH COUNCIL (MRC); TSE SYSTEMS GMBH; UK;

Finalità del progetto: Il progetto PhenoScale: "Large-scale, high-throughput automated systems for phenotyping mouse models of human disease" e' un programma di ricerca finanziato dalla Commissione Europea (FP7). Questo progetto si occupa della messa a punto di metodologie automatizzate per il monitoraggio su larga scala di abilità motorie, metabolismo e alte funzioni cognitive del topo, misurati nella gabbia di residenza. Il progetto si svolge in collaborazione tra una ditta che fornisce strumenti di misurazione del comportamento (TSE Systems, Bad Homburg, Germany) e quattro centri di ricerca europei (CNR, Monterotondo, Italy; IIT, Genova, Italy; HMGU, Muenchen, Germany; MRC, Harwell, UK).
Risultati ottenuti: E' stato osservato che, mentre la performance sul Rotarod risultava piuttosto simile tra topi HD e controlli, i mutanti HD mostravano invece un deficit motorio in età precoce se misurato con le ruote di attività. Allo stesso modo alcuni parametri di attività sulle ruote mostravano deficit nei mutanti SOD1 che non erano stati messi in evidenza dai test sul Rotarod. Da questi risultati si evince che e' possibile svelare deficit motori in questi modelli di patologie se misurati con le ruote nelle gabbie di residenza anche in stadi pre-sintomatici. Questo nuovo approccio potrebbe anche essere applicato ad altri modelli di malattie neurodegenerative caratterizzati da specifici deficit motori. I risultati di tali esperimenti sono stati presentati ai vari Phenoscale meetings e a convegni internazionali ed inoltre pubblicati o in via di pubblicazione su riviste scientifiche: ABSTRACTS -I Heise1, L Garbugino2, S Wells1, IR Meredith1, PM Nolan1, S Mandillo2, GP Tocchini-Valentini2 Automated motor function phenotyping in mice via voluntary wheel running. IBANGS (International Behavioural and neural Genetics Society) Annual meeting, Rome, May 10-14, 2011. -L Garbugino1, I Heise2, S Wells2, IR Meredith2, PM Nolan2, GP Tocchini-Valentini1, S Mandillo1 Automated motor function phenotyping in mice via voluntary wheel running. EUMODIC Final meeting. Geneva, 21-22 November 2011. ORAL PRESENTATIONS -Mandillo S (2010). Motor phenotypes in mice lacking GPR37, a receptor involved in Parkinson's disease. Phenoscale Annual Meeting, IIT Genova, Italy, 4-5 February 2010. -Mandillo S (2012). Non motor phenotypes of mice lacking the Parkinson's associated GPR37 receptor: effect of age and gender. Phenoscale Annual Meeting, IIT Rome, Italy, 24-25 January 2012. PUBLISHED ARTICLES -Maggi S, Garbugino L, Heise I, Nieus T, Balci F, Wells S, Tocchini-Valentini GP, Mandillo S, Nolan PM, Tucci V (2013). A cross-laboratory investigation of timing endophenotypes in mouse behavior. Timing & Time Perception (2013) DOI:10.1163/22134468-00002007 -Silvia Mandillo2*, Ines Heise1*, Luciana Garbugino2*, Glauco P. Tocchini-Valentini2, A. Giuliani3, Sara Wells1, Patrick M. Nolan1 . Early motor deficits in mouse disease models are reliably uncovered using an automated home cage wheel-running system: a cross-laboratory validation. Disease Models and Mechanisms (under revision)
Attività svolta: La sottoscritta ha coordinato il lavoro del gruppo che si occupa dell'analisi di comportamenti motori (Phenoscale System PSS009 MO - Motor skills) attraverso la messa a punto e l'uso di ruote di attività (Workpackage WP2-Validation and refinement of systems and Workpackage WP3 - Development of Standard Operating Procedures for systems). E' stata analizzata l'attività motoria esponendo i topi per tre settimane all'uso volontario di ruote standard (2 settimane di abituazione) e di ruote complesse (1 settimana) ovvero ruote alle quali mancavano alcuni pioli, rendendo così più difficile la coordinazione durante la corsa. L'analisi comportamentale è stata condotta su quattro ceppi inbred di topi usati come riferimento (C57BL6/N, C57BL6/J, C3H/HeH, 129P2Ola) e due linee di topi mutanti: TgN(HD82Gln)81Dbo (modello di malattia di Huntington, HD) e Tg(SOD1G93A)dl1/GurJ (modello di SLA, sclerosi laterale amiotrofica, SOD1). L'attività sulle ruote è stata anche confrontata con la performance degli animali sul Rotarod, il test più comunemente usato per valutare la coordinazione motoria. Vari parametri motori sono stati considerati per verificare quale dei due test fosse più rappresentativo per valutare la funzione motoria delle due linee mutanti a varie età. Sono state inoltre valutate le funzioni cognitive e la percezione di intervalli di tempo negli stessi ceppi inbred e nei topi mutanti modello di HD e SLA atraverso l'uso di gabbie per il condizionamento operante dotate di specico software (Phenoscale System PSS009 COWE - Cognition and Welfare).

EUMODIC - The European Mouse Disease Clinic: A distributed phenotyping resource for studying human disease

Ruolo: Partecipante Progetto
Sito web attività: http://www.europhenome.org/
Perodo di partecipazione all'attività: 02/2007 - 01/2012
Organizzazioni coinvolte: ANI.RHONE-ALPES; AUTONOMOUS UNIVERSITY OF BARCELONA; CENTER FOR INTEGRATIVE GENOMICS; EUROPEAN MOLECULAR BIOLOGY LABORATORY MONTEROTONDO; FRANCE; FRANCE; FRANCE; GERMANY; GERMANY; GREECE.; HELMHOLTZ ZENTRUM MüNCHEN; HELMHOLTZ-CENTRE FOR INFECTION RESEARCH; INSTITUT CLINIQUE DE LA SOURIS; INSTITUT DE TRANSGENOSE; ISRAEL; ITALY; ITALY; ITALY; MRC HARWELL; NATIONAL RESEARCH COUNCIL; RESEARCH CENTRE "ALEXANDER FLEMING"; SPAIN; SPAIN; SPANISH NATIONAL CANCER RESEARCH CENTRE; SWITZERLAND; TEL AVIV UNIVERSITY; TELETHON INSTITUTE OF GENETICS AND MEDICINE; THE WELLCOME TRUST SANGER INSTITUTE; UK; UK; UK; UK; UNIVERSITY OF CAMBRIDGE; UNIVERSITY OF MANCHESTER;

Finalità del progetto: EUMODIC stands for the European Mouse Disease Clinic: A distributed phenotyping resource for studying human disease. EUMODIC has brought together a large consortium of 18 research institutes in 8 European countries who are experts in the field of mouse functional genomics and phenotyping. EUMODIC will undertake a primary phenotype assessment of 500 mouse mutant lines. Phenotyping of further mutant lines will be continued by the International Mouse Phenotyping Consortium (IMPC) http://www.mousephenotype.org/. Mutant lines will be made available from another EU initiative, the EUCOMM (European Conditional Mouse Mutagenesis) project which aims to produce conditional mutations in 20,000 mouse genes. In addition, a number of these mutant lines will be subject to a more in depth secondary phenotype assessment. The EUMODIC consortium will build on the work in the EUMORPHIA project that delivered a comprehensive database EMPReSS - of Standard Operating Procedures (SOPs) that can be used to determine the phenotype of a mouse. EUMODIC has developed a selection of these screens, EMPReSSslim, which is structured for comprehensive, primary, high throughput phenotyping of large numbers of mice. Primary phenotype assessment using EMPReSSslim will be undertaken in four large-scale phenotyping centres at the HMGU, Germany; ICS, France; MRC Harwell, UK and the Sanger Institute, UK. This primary phenotyping data will then be made publicly available on EuroPhenome http://www.europhenome.org/. A distributed network of centres with in depth expertise in a number of phenotyping domains will undertake more complex, secondary phenotyping screens and apply them to a subset of the mice which have shown interesting phenotypes in the primary screen.

Risultati ottenuti: Results of all these experiments as well as the description and discussion on the procedures used have been presented to all EUMODIC meetings and to international scientific conferences and workshops. Results have also been published on major scientific journals. ORAL PRESENTATIONS -Mandillo S (2007). Behavioural alterations in mice lacking the Parkinson's disease associated GPR37 receptor. EUMODIC Start Up Meeting Barcelona, Spain. 23 February 2007. -Mandillo S (2007). Mice lacking the parkin associated receptor GPR37 show behavioral abnormalities linked to dopaminergic system alterations. Invited speaker at the Symposium: "Behavioural phenotyping for alterations in brain function" of the 9th Annual Meeting of the International Behavioural and Neural Genetics Society (IBANGS) Doorwerth, The Netherlands. 21-25 May 2007. -Mandillo S (2009). WP 2.5 Behaviour, cognition and nervous system. EUMODIC Annual Meeting, Athens, Greece, 2-4 March, 2009. -Mandillo S (2009). Behavioral characterization of knock-out mutant mice for a Parkinson's disease-associated receptor. Invited speaker to XV National Congress of Experimental Psychology Italian Psychology Association (AIP), Symposium "Behavioral phenotypes in animal models", Chieti, Italy, 24-26 Sept. 2009. -Mandillo S (2010). Motor phenotypes in mice lacking GPR37, a receptor involved in Parkinson's disease. Phenoscale Annual Meeting, IIT Genova, Italy, 4-5 February 2010. -Mandillo S (2010). Behavioral characterization of mutant mouse models of human neurodegenerative diseases. CNR-EBRI-EMBL-ICGEB Monterotondo Workshop 2010, 18-19 March 2010. -Mandillo S (2011). Behavioural characterization of EUMODIC mutant lines. EUMODIC Annual Meeting, Barcelona, Spain, 2-3 March, 2011. -Mandillo S (2012). Non motor phenotypes of mice lacking the Parkinson's associated GPR37 receptor: effect of age and gender. Phenoscale Annual Meeting, Rome, Italy, 24-25 January 2012. PUBLISHED ARTICLES 1.Mandillo S, Golini E, Marazziti D, Di Pietro C, Matteoni R, Tocchini-Valentini GP (2013). Mice lacking the Parkinson's related GPR37/PAEL receptor show non-motor behavioral phenotypes: age and gender effect. Genes Brain Behav. 2013 Jun;12(4):465-77. 2.Marazziti D, Di Pietro C, Golini E, Mandillo S, La Sala G, Matteoni R, Tocchini-Valentini GP. (2013). Precocious cerebellum development and improved motor functions in mice lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor. Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16486-16491. Epub 2013 Sep 23. 3.Marazziti D, Di Pietro C, Mandillo S, Golini E, Matteoni R, Tocchini-Valentini GP (2011). Absence of the GPR37/PAEL receptor impairs striatal Akt and ERK2 phosphorylation, DeltaFosB expression, and conditioned place preference to amphetamine and cocaine. FASEB J. 25(6): 2071-81. 4. Marazziti D, Golini E, Mandillo S, Magrelli A, Witke W, Matteoni R, Tocchini-Valentini G (2004). Altered dopamine signaling and MPTP resistance in mice lacking the Parkinson's disease-associated GPR37/parkin-associated endothelin-like receptor. Proc. Natl. Acad. Sci. USA 101 (27): 10189-10194. July 2004. 5.Marazziti D, Mandillo S, Di Pietro C, Golini E, Matteoni R, Tocchini-Valentini G P (2007) GPR37 associates with the dopamine transporter to modulate dopamine uptake and behavioral responses to dopaminergic drugs. Proc. Natl. Acad. Sci. USA (PNAS), 104 (23): 9846-9851. 6.Morgan H, Beck T, Blake A, Gates H, Adams N, Debouzy G, Leblanc S, Lengger C, Maier H, Melvin D, Meziane H, Richardson D, Wells S, White J, Wood J; EUMODIC Consortium, de Angelis MH, Brown SD, Hancock JM, Mallon AM (2010). EuroPhenome: a repository for high-throughput mouse phenotyping data. Nucleic Acids Res. 38 (Database issue): D577-85. Epub 2009 Nov 23. 7.Simon MM, Greenaway S, White JK, Fuchs H, Gailus-Durner V, Sorg T, Wong K, Bedu E, Cartwright EJ, Dacquin R, Djebali S, Estabel J, Graw J, Ingham NJ, Jackson IJ, Lengeling A, Mandillo S, Marvel J, Meziane H, Preitner F, Puk O, Roux M, Adams DJ, Atkins S, Ayadi A, Becker L, Andrew Blake1, Brooker D, Cater H, Champy M-F, Combe R, Danecek P, di Fenza A, Gates H, Gerdin A-K, Golini E, Hancock JM, Hans W, Hölter SM, Hough T, Jurdic P, Keane TM, Morgan H, Müller W, Frauke Neff F, Nicholson G, Pasche B, Roberson L-A, Rozman J, Sanderson M, Santos L, Selloum M, Shannon C, Southwell A, Tocchini-Valentini GP, Vancollie VE, Wells S, Westerberg H, Wurst W, Zi M, Yalcin B, Ramirez-Solis R, Steel KP, Mallon A-M, Hrab de Angelis M, Herault Y and Brown SDM (2013). A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains. Genome Biology, 2013 Jul 31;14(7):R82. [Epub ahead of print].

Attività svolta: For the entire project I have been involved in the development and validation of secondary phenotyping screens actively contributing within the activities of workpackage 2.5 "Behaviour, cognition and nervous system". During the first part of the project we have set up equipment and procedures at CNR to perform the following tests: rotarod to evaluate coordination and motor learning, fear conditioning to asses emotional memory, light/dark box to uncover anxiety-like behaviours, Morris water maze to study spatial memory. All these tests have been previously applied and validated on two inbred strains (C57BL/6J and C57BL/6NTac). Interesting and significant strain differences have been observed in all these procedures. These findings provide relevant information on the baseline behavior of strains used as mutant genetic background. Results of these experiments have been published in Genome Biology (Simon et al. 2013).

Some of these tests have also been validated and performed on GPR37 and GPR37-L1 knockout mutant mice. These mice lack two orphan G-protein coupled receptors that are highly expressed in the mammalian central nervous system. In particular, GPR37 is involved in the pathophysiology of Parkinson's disease and it modulates several aspects of dopaminergic system functions (Marazziti et al., 2004; 2007; 2011). These two strains could contribute to elucidate the role of GPR37 family receptors in the pathophisiology of Parkinson's disease and possibly other disorders characterised by motor, emotional or cognitive disturbances (Mandillo et al., 2013; Marazziti et al., 2013). Additionally, new secondary phenotyping procedures were developed at CNR: olfactory tests and colon motility tests to evaluate non-motor phenotypes highly relevant to model early symptoms of Parkinson's disease and possibly other neurodegenerative syndromes (Mandillo et al., 2013); and the set up of an automated system for home cage monitoring of motor activity and motor skills through the analysis of running wheel activity. This new system was validated in 4 inbred reference strains (C57BL6/N, C57BL6/J, C3H/HeH, 129P2Ola) and two lines of mutants: TgN(HD82Gln)81Dbo (model of Huntington disease) and Tg(SOD1G93A)dl1/GurJ (model of amyotrophic lateral sclerosis) also as part of the Phenoscale project (FP7).

Finally, in the last part of the project, the EUCOMM/EUMODIC lines Zranb2 and Fto have been phenotyped. Zranb2 (zinc finger, RAN-binding domain-containing protein 2) and Fto (fat mass and obesity associated) male and female KO mutant mice at the age of 8-12 weeks were tested in selected secondary behavioural phenotyping screens including, open field, light/dark test and elevated plus maze to assess anxiety-like behaviors, fear conditioning to evaluate emotional memory, and running wheel activity associated with daily monitoring of food intake. Zranb2 is widely expressed and it has a role as regulator of alternative splicing. It was found that Zranb2 female mutants show higher levels of anxiety-like behaviours and both male and female mutants show possible deficits in emotional memory. Fto has been associated to the risk of obesity in humans. It is ubiquitously expressed in mammalian brain, namely cerebellum, hippocampus and hypothalamus. Fto homzygous mice show higher perinatal mortality and a significant reduction in body weight associated to increased food intake and wheel running activity. It can be hypothesized a role of Fto in metabolism and energy balance regulation.

Within the EUMODIC project I have been a Member of Animal Welfare Advisory Board involved in the following activities: Assessment of animal welfare between institutes: questionnaires and collection of protocols, implementation of cage environmental enrichment; Development of Guidelines for optimal husbandry: production of a "welfare catalogue" by collecting phenotype relevant data already published and existing in the consortium and presented on a common database (www.mousewelfareterms.org); Development of Guidelines for humane endpoints to monitor, define and determine severity limits clearly; Dissemination of welfare information; Monitor status of implementation of EU Directive 2010/63/EU on Protection of animals for scientific purposes.

During the EUMODIC project I have participated and presented results and activity reports to the following meetings: PRIME-EuroPhenome, Munich, Germany 7-9 Sept. 2006; EUMODIC Start-up meeting, Barcelona, Spain 22-23 Feb. 2007; EUMODIC annual meeting, Le Bischenberg, Strasbourg, France 11-12 March 2008; EUMODIC Clinics Management Meeting, Harwell, UK 24-25 Sept. 2008; EUMODIC annual meeting, Athens, Greece 2-4 March 2009; EUMODIC mid-year meeting Harwell, UK 16-17 June 2009; EUMODIC annual meeting, Brussels, Belgium 25-26 march 2010; EUMODIC annual meeting, Barcelona, Spain 2-3 March 2011; EUMODIC Final meeting, Geneva, Suisse 21-22 Nov 2011.

EUMORPHIA - European Union Mouse Research for Public Health and Industrial Applications

Ruolo: Partecipante Progetto
Perodo di partecipazione all'attività: 10/2002 - 03/2006
Organizzazioni coinvolte: AMSTERDAM; ANIMAGE CERMEP; BRAUNSCHWEIG; CAMBRIDGE; CNG; CNIO; CNRS INSTITUT DE TRANSGENOSE; EDINBURGH; EMBL MOUSE BIOLOGY; ENS LYON LABORATORY OF MOLECULAR BIOLOGY OF THE CELL; EVRY; FRANCE; FRANCE; FRANCE; FRANCE; FRANCE; GBF; GERMANY; GERMANY; GSF (IDG & IEG); IBC-CNR; INSTITUT CLINIQUE DE LA SOURIS; INSTITUT PASTEUR; ITALY; ITALY; KAROLINSKA INSTITUTE; LYON; LYON; LYON; MADRID; MONTEROTONDO; MONTEROTONDO; MRC HARWELL (MGU AND MLC); MRC HUMAN GENETICS UNIT; MUNICH; NETHERLANDS; NKI; SPAIN; STRASBOURG; SWEDEN; SWITZERLAND; SWITZERLAND; THE WELLCOME TRUST SANGER INSTITUTE; UK; UK; UK; UK. HTTP://CORDIS.EUROPA.EU/PROJECTS/RCN/64756_EN.HTML; UNIVERSITY OF GENEVA; UNIVERSITY OF LAUSANNE; UNIVERSITY OF MANCHESTER;

Finalità del progetto: Understanding human molecular physiology and pathology through integrated functional genomics in the mouse model. An integrated approach applying phenotyping, mutagenesis, informatics to development of mouse models/understanding of human physiology/disease, focusing on the development/standardisation of primary and secondary phenotyping protocols for all body systems in the mouse underpinned by substantial networking involving working groups from EU and abroad bringing expertise to bear in the development/validation of screens. The programme is supported by new informatics developments within research/networking focusing on provision of tools for dissemination, acquisition and querying of phenotype data. The training programme bolsters research bringing new skills from diverse areas e.g. veterinary and clinical medicine to mouse biology and the study of disease models, while also creating a new cadre of scientists trained in mouse genetics. EUMORPHIA prepares the EU community for future challenges regarding Genomes for Human Health.
Risultati ottenuti: The results of this collaborative effort have been presented to several meetings, collected in two databases (EMPReSS, www.empress.har.mrc.ac.uk and EuroPhenome, www.europhenome.org) and published in: 1. Mandillo S, Tucci V, Holter SM, Meziane H, Al Banchaabouchi M, Kallnik M, Lad HV, Nolan PM, Ouagazzal AM, Coghill EL, Gale K, Golini E, Jacquot S, Krezel W, Parker A, Riet F, Schneider I, Marazziti D, Auwerx JH, Brown SD, Chambon P, Rosenthal N, Tocchini-Valentini G, Wurst W (2008). Reliability, Robustness, and Reproducibility in mouse behavioral phenotyping: a cross-laboratory study. Physiological Genomics, 34: 243-255. 2. Brown S. et al. and members of the EUMORPHIA consortium (2006). EUMORPHIA and the European Mouse Phenotyping Resource for Standardized Screens (EMPRReSS) Chapter 13 in: Standards of Mouse Model Phenotyping. Edited by M. Hrabe' de Angelis, P. Chambon and S. Brown, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. 3. Brown S. et al. and members of EUMORPHIA consortium. (2005). EMPReSS: standardised phenotype screens for functional annotation of the mouse genome. Nature Genetics, 37 (11): 1155.
Attività svolta: Within Eumorphia we have developed a new robust primary screening platform, EMPReSS - European Mouse Phenotyping Resource for Standardised Screens. This primary screen incorporates over 150 new SOPs (Standard Operating Procedures) and associated annexes and appendices, many validated on a cohort of inbred strains across a number of laboratories. EMPReSS covers all of the major body systems, as well as generic approaches in imaging, pathology and gene expression (Brown et al., 2005; 2006). Our group at IBC-CNR was involved in the activities of Workpackages WP9 (PNS and skeletal muscle) and WP10 (Behaviour and Cognition). We developed the SOPs for a battery of 9 behavioral tests (Open Field, SHIRPA, Grip test, Rotarod, Y-maze, Pre-pulse inhibition, Tail flick, Tail suspension, Swim ability) to assess neurological and behavioural functions in a primary phenotyping screen. The battery of tests was validated in four inbred mouse strains - C57BL/6J, C3HeB/FeJ, BALB/cByJ, 129S2/SvPas across five European laboratories (CNR, MRC. ICS, GSF, EMBL) (Mandillo et al., 2008). Beside research activities I have also participated to networking activities through training programs as tutor or trainee: SHIRPA training, September 2003, Harwell, UK; Medical Imaging for Small Animals, June 2004, Lyon, France; Behavioural Phenotyping, April 2005, Strasbourg, France. During the four years of the project I have participated and presented results and activity reports to the following meetings: First General Assembly, 15-17 Jan 2003, Strasbourg, France; WP9&10 meeting, 11 July 2003, Rome, Italy; First Annual Project Meeting, 6-8 Oct 2003, London, UK; WP9&10 meeting, 15 Dec 2003, Rome, Italy; Second General Assembly, 18-24 March 2004, Munich, Germany; WP9&10 meeting, 23 April 2004, Rome, Italy; WP9&10 meeting, 2-3 July 2003, Lyon, France; Second Annual Project Meeting, 5-7 Oct 2004, Heathrow, UK; WP9&10 meeting, 9-10 Dec 2004, Rome, Italy; Third General Assembly, 16-17 March 2005, Madrid, Spain; WP9&10 meeting, 29 Nov 2005, Rome, Italy; Third Annual Project Meeting, 23-24 Feb 2006, Barcelona, Spain.


Research activities classification (ERC)

LIFE SCIENCES
NEUROSCIENCES AND NEURAL DISORDERS: NEUROBIOLOGY, NEUROANATOMY, NEUROPHYSIOLOGY, NEUROCHEMISTRY, NEUROPHARMACOLOGY, NEUROIMAGING, SYSTEMS NEUROSCIENCE, NEUROLOGICAL DISORDERS, PSYCHIATRY

Prodotti della ricerca

Casola I 1.; Scicchitano B.M. 2; Lepore E. 1; Mandillo S. 3; Golini E. 3; Nicoletti C. 1; Barberi L.1; Dobrowolny G. 1; Musaro A. 1,4

Circulating myomirs in muscle denervation: From surgical to als pathological condition

(2021) in Cells
Buonfiglio M.; Albini M.; Mandillo S.; Brighina F.; Di Sabato F.; Di Bonaventura C.; Giallonardo A.T.; Avanzini G.

Differences in visual information processing style between Idiopathic Generalized Epilepsy with and without photosensitivity

(2021) in Epilepsy & behavior (Print)
La Cognata Valentina; Golini Elisabetta; Iemmolo Rosario; Balletta Sara; Morello Giovanna; De Rosa Carla; Villari Ambra; Marinelli Sara; Vacca Valentina; Bonaventura Gabriele; Dell'Albani Paola; Aronica Eleonora; Mammano Fabio; Mandillo Silvia; Cavallaro Sebastiano

CXCR2 increases in ALS cortical neurons and its inhibition prevents motor neurons degeneration in vitro and improves neuromuscular function in SOD1G93A mice

(2021) in Neurobiology of disease
B. Cardinali (1), C. Provenzano (1), Mariapaola Izzo (1), C. Voellenkle (2), J. Battistini (1), G. Strimpakos (1), E. Golini (1), S. Mandillo (1), F. Scavizzi (1), M. Raspa (1), A. Perfetti (2), D. Baci (2), D. Lazarevic (3), J. Garcia-Manteiga (3), G. Gourdon (4) F. Martelli (2), G. Falcone (1)

Inducible CRISPR/Cas9 strategy mediates efficient gene editing of trinucleotide repeat expansion in DMPK locus

(2021) Pathogenesis and Therapies of Neuromuscular Diseases, 18th Interuniversitary Institute of Myology (IIM) Meeting, On-line, 22-24 Ottobre 2021
E. Golini1, M. Rigamonti2, F. Iannello2, C. De Rosa1, F. Scavizzi1, M. Raspa1, S. Mandillo1

Home cage detection of sleep disturbances in a mouse model of ALS

(2021) 3rd CCP Phenogenomics conference 2021, 16-17/09/2021
Mandillo Silvia

A non-invasive digital biomarker for the detection of rest disturbances in the SOD1G93A mouse model of ALS

(2021) Research Topic on Home Cage Monitoring, Frontiers Webinar, 20/05/2021
Beatrice Cardinali 1, Claudia Provenzano 1, Mariapaola Izzo 1, Jonathan Battistini 1, Georgios Strimpakos 1, Elisabetta Golini 1, Silvia Mandillo*1, Ferdinando Scavizzi 1, Marcello Raspa 1, Christine Voellenkle 2, Alessandra Perfetti 2, Denisa Baci 2, Fabio Martelli 2, Genevieve Gourdon 3, Germana Falcone 1

Gene Therapy Strategies For Myotonic Dystrophy Type 1

(2021) "Mechanistic Insights into Neurological Disorders and New Therapeutic Strategies", DSB Conference, CNR Rome, Italy, 07-08/07/2021
Silvia Mandillo

The potential of home cage monitoring to screen mice for sleep disturbances

(2021) "Mouse Genetics and Genomics Medicine", IMPC 10th Anniversary Virtual Conference, 23-24/09/2021
Golini E 1, Rigamonti M 2, Iannello F 2, De Rosa C 1, Scavizzi F 1, Raspa M 1, Mandillo S 1

A non-invasive digital biomarker for the detection of rest disturbances in the SOD1G93A mouse model of ALS

(2020) in Frontiers in neuroscience (Online)
Silvia Mandillo

DVC technology to detect digital biomarkers in a mouse model of ALS

(2020) Accelerating animal model research by leveraging home cage monitoring, Webinar Tecniplast - Mary Ann Liebert Inc. Publishers, 22/04/2020
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