The MIB will be hosting two speakers on Friday 20 July, 12-1pm (in the MIB Lecture Theatre)
Speaker 1: Déborah Tribouillard-Tanvier (CNRS, Institut de Biochimie et Génétique Cellulaires, France).
Seminar Title: Yeast as a system for modeling mitochondrial disease mechanisms and discovering therapies.
Speaker 2: Jean-Paul di Rago (CNRS, Institut de Biochimie et Génétique Cellulaires, France)
Seminar Title: Mitochondrial to nuclear gene transfer via synthetic evolution
Abstracts
Yeast as a system for modeling mitochondrial disease mechanisms and discovering therapies.
Mitochondrial diseases are severe and largely untreatable. Due to the many essential processes carried out by mitochondria and the complex cellular systems that support these processes, these diseases are diverse, pleiotropic, and challenging to study. As a facultative aerobe amenable to mitochondrial and nuclear genome manipulations, and owing to the high level of conservation of mitochondrial components and processes, Saccharomyces cerevisiae is an excellent model system for studying and resolving the molecular basis of diseases associated to mitochondrial dysfunctions. Additionally, it affords the possibility to identify potential therapeutic targets by way of genetic and chemical screens. Using this system I investigated the pathogenic mechanisms of disorders associated to mutations in the mitochondrial ATP6 gene and defects in the remodeling of cardiolipin, a phospholipid with multiple roles in mitochondria. A number of chemical compounds that hold promise for the development of therapeutic strategies against these diseases have been identified.
Short bio: Déborah Tribouillard-Tanvier is currently research associate at the Institut National pour la Santé et la Recherche Médicale (INSERM). She received her PhD in Biological Sciences from the University of Rennes (France) in 2007. She then performed postdoctoral research in Rockies Mountain Laboratories, Hamilton, MT (USA), working on prion diseases. She became a research associate at the INSERM in 2012 and joined the laboratory of Jean-Paul di Rago in 2015 at the Institut de Biochimie et Génétique Cellulaires in Bordeaux, France. Her current research focuses on mitochondrial diseases using yeast a model system to better understand their mechanisms and help the development of therapeutic solutions.
Mitochondrial to nuclear gene transfer via synthetic evolution
Mitochondria, the centers of cellular energy production, have transferred the majority of their own genetic material to the nuclear genome during evolution. Yet a handful of genes remain in all mitochondrial genomes, despite their susceptibility to damaging by metabolic byproducts and mutations. The consequences of mtDNA mutations are significant: they are implicated in a range of severe diseases, and the mutations accumulated during a lifetime are believed to lead to neurodegenerative disorders and the ageing process itself. This raises the question of why the mitochondrial genome still exists, despite the potentially severe consequences on fitness in all eukaryotes, and what are the cellular processes that limit or support mitochondrial gene expression from the nucleus. These questions can be answered by synthetic 'allotopic' expression of these genes from the protected environment of the nucleus. Yeast is uniquely suited to study this problem because it is one of few organisms where mtDNA can be manipulated, and is amenable to genomic and synthetic biology techniques. Using this approach, we found that successful transfer of mtDNA to the nucleus requires adaptations not only in the allotopic protein, but also in several cellular processes to protect it from degradation both outside and inside the organelle.
Short bio: Jean-Paul di Rago is currently a research director at the Centre National de la Recherche Scientifique (CNRS) at the Institut de Biochimie et Génétique Cellulaires in Bordeaux, France. He received his PhD in Biological Sciences from the University of Louvain, Louvain-la-Neuve (Belgium) in 1988. He then performed postdoctoral research in the lab of Professor Piotr Slonimski in Gif-Sur-Yvette (Paris, France), working on yeast mitochondrial genetics. He became a research associate at the CNRS in 1990. He was a guest scientist at Dartmouth Medical School (NH, USA) in 1992. In 1999, he moved to Bordeaux where he became a group leader and was promoted to research director in 2001. His current research focuses on mitochondrial ATP synthase biogenesis, mitochondrial genome evolution, and the modelling in yeast of human diseases associated to mitochondrial dysfunction to better understand their mechanisms and help the development of therapeutic solutions.
