Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

Final Activity Report Summary - MITOMED-TRAIN (Early stage training in mitochondrial medicine)

Mitochondrial medicine is a growing field that is anticipated to give rise to many future breakthroughs in medicine. We used an interdisciplinary approach to study the link between mitochondrial dysfunction and human disease. Several rare metabolic diseases are caused my mitochondrial dysfunction, which is also implicated in a wide variety of age associated human diseases, such as heart failure, diabetes mellitus type II and Parkinson's disease and even implicated as one of the causes of the normal ageing process.

The mitochondrial medicine centre combined a multitude of disciplines to attack a single biological problem, i.e. mitochondrial disease. In this way we approached the subject from several different angles, thus significantly increasing the chances for real breakthroughs. Within the centre we collected internationally leading expertise dealing with mitochondrial medicine from molecule to patient.

The MITOMED-TRAIN programme provided graduate training of the highest calibre. There was a structured system of mentoring and monitoring of progress, with specific goals and milestones at all stages of the PhD programme. Students were closely supervised and expected to gain independence over the years. They learnt how to report their findings in peer reviewed scientific journals, how to design a successful experiment, how to present their research at international conferences etc. Graduate students in the programme were submerged in an internationally leading scientific environment with access to state of the art techniques and graduate courses taught by internationally leading scientists.

The graduate projects themselves focussed on different aspects of mitochondrial function in health and disease. It has been shown that in mice a lot of mutations in the mitochondrial genome (mtDNA) leads to symptoms of ageing.

The first research project, by Ivana Bratic, aimed to study the impact of the same kind of high mutation rate in the small worm and model the organism caenorhabditis elegans. Using this simpler organism it was anticipated to be easier to identify genes and pathways involved in ageing.

The second graduate project, Twinkle, by Dominika Kasperska, focussed on creating three-dimensional models of how mitochondrial proteins looked. She contributed to a new method to achieve this and used the method to determine the structure of one of the key proteins in mitochondrial function.

Student Javier Miralles aimed to investigate the molecular mechanisms of how mtDNA replicated. He was able to produce a test-tube model of the entire replication machinery, which could be used to understand how the replication was regulated.

Student Paulina Matikainen's research project had the objective to investigate the connections between the mitochondrial and nuclear transcription apparatus, with the term transcription describing how the cell transferred genomic information to the protein synthesis machinery. How could gene expression in the nucleus be coordinated with mitochondrial requirements? During her time as a Marie Curie ESR, Paulina made very important discoveries and established a new model for the initiation of mtDNA replication in mammalian cells.

Finally, the focus of the fifth project, by Christakos Panayiotou, was on the identification of new protein sequences predicted to be involved in the salvage pathways of nucleotides, i.e. of the building blocks of our deoxyribonucleic acid (DNA). Christakos was involved in the design of a new programme that was able to search many proteins for patterns that indicated they were involved in these pathways. Using this programme, he was able to identify seven possible new proteins of interest.

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