Université de Strasbourg

Christelle Golzio & Hélène Puccio

Biography - Christelle Golzio

Institute of Genetics and Molecular and Cellular Biology (IGBMC), University of Strasbourg, CNRS & Inserm

Christelle Golzio, USIAS Fellow 2019

Dr. Christelle Golzio studied for her thesis with Professor Stanislas Lyonnet and his team at the hôpital Necker-Enfants malades (Necker hospital for sick children) where she worked on FGF (fibroblast growth factors) signalling in cardiac morphogenesis and the study of congenital cardiopathies. In 2009 she obtained her doctorate in human genetics and development at Paris Descartes University (France). She subsequently carried out her post-doctoral training at Duke University (North Carolina, USA) where she studied the genetical architecture of complex diseases including gene interaction, dosage effects and determining variant pathogenicity identified among persons with rare diseases.  

In 2014 she won the NARSAD Young Investigator Grant and was made senior lecturer in the Department of Psychiatry at Duke University, where she led a research group at the Center for Human Disease Modeling. With a grant from the LabEx INRT (Integrative Biology: Nuclear dynamics, Regenerative and Translational Medicine), she transferred her laboratory to the IGBMC. Her team is part of the LabEx INRT. In 2017, she obtained the habilitation à diriger des recherches (accreditation to lead research) and was named research scientist at the French National Institute of Health and Medical Research (Inserm).

Her research work concentrates on the study of chromosomal rearrangements in syndromic forms of autism. More specifically, the aim is to understand how genetic variations can have an impact on the development and homeostasis of the central nervous and enteric system.

Biography - Hélène Puccio

Institute of Genetics and Molecular and Cellular Biology (IGBMC), University of Strasbourg, CNRS & Inserm and NeuroMyoGene Institute (INMG), Claude Bernard Lyon 1 University

Hélène Puccio, USIAS Fellow 2019

Dr. Hélène Puccio obtained her PhD in genetics from Harvard University (USA) in 1998, on the identification and characterisation of a family of novel dystrophin-related and associated proteins, the dystrobrevins. She then joined the group of Michel Koenig at the IGBMC to work on the molecular pathogenesis of Friedreich ataxia (FA).  In 2001, she was appointed Inserm – the French National Institute of Health and Medical Research - research associate and has since been the principal investigator on the FA project. In 2008, she was promoted to Inserm Research Director. Her research interest focuses on understanding the pathophysiological mechanisms implicated in recessive ataxias linked to mitochondrial dysfunction. Her team has made significant contributions advancing fundamental knowledge on Fe-S cluster and CoQ10 biosynthesis, pathophysiological pathways involved in diseases and developing novel therapeutic approaches.

Hélène Puccio has received a number of awards, including the Pediatric Pathology Prize (2005), the "Equipe FRM” label (2005), an ERC Starting Grant Award (2007), the Dr. Jean Toy Prize from the French Academy of Sciences (2008), the Prix de l’Académie Rhénane (2014), the Prix “La Recherche - La science en avance” (2015) and the Prix Antoine Lacassagne of the Collège de France (2016).

Project - In vivo modelling of a rare recessive ataxia linked to mitochondrial dysfunction utilizing zebrafish

01/10/2019 - 30/09/2021

ARCA2 (autosomal recessive cerebellar ataxia type 2) is a rare cerebellar ataxia characterised by severe cerebellar atrophy and mild deficiency in Coenzyme Q10 (CoQ10), with large phenotypic variability. ARCA2 is due to mutations in the gene encoding for the protein COQ8A, a mitochondrial protein involved in Coenzyme Q biosynthesis. Different types of mutations (missense, non-sense, frameshift) have been identified, but no genotype-phenotype correlation has been established. Given the high phenotypic variability observed in the affected individuals, as well as the relatively mild phenotype in the mouse model, Dr. Golzio and Dr. Puccio hypothesise that 1) ARCA2 is not due solely to a loss-of-function of COQ8A and that some missense COQ8A mutations might be more deleterious than a complete loss of function (i.e. dominant-negative or gain-of-function) and 2) there might be a developmental component that could not be recapitulated in the knockout mouse model. They propose to address these two hypotheses using the zebrafish as an in vivo model.

By generating these novel vertebrate models and performing in vivo complementation to assess the pathogenicity of the mutations, it will be possible to gain functional insight into the basic biology of COQ8A as well as the functional consequences of a series of mutations associated with the human disease. The completion of the project will help to understand better the phenotypic spectrum of ARCA2. On the long-term and beyond the scope of this proposal, the use of the disease models generated during this award period for high-throughput in vivo screen of candidate therapeutic molecules may be envisaged.

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Investissements d'Avenir