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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - REMIX (Regulation of mitochondrial expression)

Teaser

Summary

The main scientific focus of REMIX network is to further understand the molecular mechanism involved in regulation of mitochondrial gene expression that is coordinated by two different genomes. The mitochondrial genome (mtDNA) encodes for key subunits of the oxidative phosphorylation system all RNA components needed for their translation. All other factors needed for mitochondrial DNA replication, DNA repair, transcription and translation are encoded in the nucleus, made in the cytoplasm and then imported into mitochondria. Dysfunction of many different components involved in the regulation of mitochondrial gene expression underlies a great variety of human diseases and modulates organismal aging. To achieve this, REMIX network has recruited 15 highly motivated early stage researcher in order to train them to become the next generation leading scientists in the field. After the recruitment REMIX fellows began a scientific training in their own laboratories, and even more importantly through network-based activities. The extensive network-based training allowed REMIX fellows to form a highly coherent group that communicate on a daily basis sharing their protocols, ideas and successes. All REMIX fellow started working on their respective research projects that are very much interconnected. Initial and preliminary results are very promising as we identified novel players and pathways involved in different steps of mitochondrial gene expression. To achieve the best possible dissemination of our goals and results, we have developed REMIX website (www.remix-itn.eu) aimed to address different audiences but also enable communication within Consortium. To maximize dissemination of results and public engagement, REMIX fellows started active social media dissemination through Facebook, Instagram and Twitter platforms, but also maintain daily bases communication within the group.

Work performed

To achieve its goals, REMIX network has recruited 15 highly motivated early stage researcher in order to train them to become the next generation leading scientists in the field of mitochondrial research. REMIX fellows began a scientific training in their own laboratories, and even more importantly through network-based activities. As a class, theyâ€™ve already attended three different soft skill training workshops: Scientific Writing, Statistical Literacy and Data Analysis and two specialized workshops: Mass Spectrometry and Drug Development courses. Majority of fellows also attended EMBO Workshop on Molecular Biology of Mitochondrial gene Expression. Training through research is extremely important part of their predoctoral education and it is accomplished through the three research work packages: (i) Novel insights into maintenance of mitochondrial genome, (ii) Molecular mechanisms of mitochondrial transcription and (iii) RNA processing and Identification of novel factor governing mitochondrial ribosomal assembly and protein synthesis. During the first half of the project, fellows started actively attending some international scientific conferences where they have presented their results and we expect this to be increasing over the second part of the REMIX project, as fellows develop their projects further.
We have also developed REMIX website (www.remix-itn.eu) aimed to address different audiences but also enable communication within Consortium. The website contains a specific section dedicated to communication and dissemination of our results where fellows post their thoughts and experiences from different events in the form of blogs. To maximize dissemination of results and public engagement, active social media dissemination started from Month 18. Three main social channels have been chosen for this means: Facebook, Instagram and Twitter. For each channel one ESR is in charge of posting and gathering news and information, but all 15 fellows are motivated to also post pro-actively. REMIX fellows created their own WhatsApp group that allowed them to coordinate many of their dissemination activities and allow daily basis communication. They participated in direct outreach activities aimed toward general public and elementary and high school students, as a part of e.g. European Researcherâ€™s Night or Light up for Mito: Global Mitochondrial Disease Awareness Week.

Final results

The overall objective of the REMIX project remained the same, we want to shed more light on the molecular mechanism regulating mitochondrial gene expression on all different levels, from mtDNA replication, to transcription and translation, but also crosstalk between nuclear and mitochondrial genomes essential for proper function of energy generating system â€“ OXPHOS. Despite encoding only 13 polypeptides, mitochondrial gene expression is in the heart of cellular energy production and defects in the synthesis, import, and modification of mitochondrial polypeptides as well as defective assembly of multi-subunit OXPHOS complexes result in devastating diseases that primarily affect tissues with a high metabolic demand, such as the nervous, muscular, cardiac, ocular and endocrine systems. These very heterogeneous diseases are very prevalent and affect children and adults alike.
REMIX project aims to understanding of the mechanisms governing the mitochondrial gene expression and its associated pathologies; we want to understand the regulation of these processes in response to metabolic demands and discover mechanisms governing crosstalk between the two genomes needed for the coordination of OXPHOS assembly. The multidisciplinary nature and technical complexity of the proposed work made it too large in scope for any individual research group, and therefore REMIX project was established to coordinate and integrate European mitochondrial gene expression research and even more importantly, to train and teach the next generation of scientists in the field of mitochondrial biology. Our multidisciplinary team, which harnesses the different expertise (genetics, molecular and cell biology, biochemistry and structural biology) of researchers across Europe, is perfectly tailored to answer these questions and preliminary results included in this periodic report clearly show this. Fifteen brilliant ESRs that joined our teams are being trained in the broad range of skills and expertise in mitochondrial biology, biochemistry and genetic and also complementary soft skills. They are and will become even more the driving force behind REMIX goals allowing them to grow into the future leaders in the field. With our ESRs working on their individual projects, but also by pooling our resources, stimulating researcher exchange and training-promoting knowledge transfer, and enhancing scientific communication between researchers with complementary expertise, we are certain to achieve REMIX goals.