Research Trainee in Mitochondrial Biology

**The Institute** The Centre for Genomic Regulation (CRG) is an international biomedical research institute of excellence, based in Barcelona, Spain, with more than 400 scientists from 44 countries. The CRG is composed by an interdisciplinary, motivated and creative scientific team which is supported both by a flexible and efficient administration and by high-end and innovative technologies. In April 2021, the Centre for Genomic Regulation (CRG) received the renewal of the 'HR Excellence in Research' Award from the European Commission. This is a recognition of the Institute's commitment to developing an HR Strategy for Researchers, designed to bring the practices and procedures in line with the principles of the European Charter for Researchers and the Code of Conduct for the Recruitment of Researchers (Charter and Code). Please, check out our Recruitment Policy **The role** **About the**lab** Group leader: Luis-Carlos Tábara, Ph.D Mitochondria, as the primary providers of cellular energy through oxidative phosphorylation (OXPHOS), are essential for metabolism and sustaining life. Throughout evolution, most genes from the ancestral mitochondrial genome have either been lost or relocated to the nuclear genome. As a result, only a compact mitochondrial DNA (mtDNA) molecule remains. In mammals, mtDNA is a circular, double-stranded molecule of 16.6 kb. This genome is inherited exclusively from the mother because paternal mtDNA is degraded and not transmitted to offspring. Despite its small size, mtDNA encodes 37 genes: 13 essential subunits of the OXPHOS system, 2 ribosomal RNAs (rRNAs), and 22 transfer RNAs (tRNAs) required for mitochondrial protein synthesis. While these mtDNA-encoded proteins represent only a fraction of the more than 90 proteins that make up the OXPHOS machinery, they are indispensable and mitochondrial energy production collapses in their absence. Unlike diploid nuclear DNA, mtDNA exists as a multicopy genome. mtDNA replicates independently of the cell cycle, a process known as "relaxed replication," resulting in a high mtDNA copy number (CN) ranging from hundreds to thousands of molecules. Factors such as ATP demand and nucleotide availability are proposed to influence mtDNA content. However, the mechanisms by which cells sense and regulate mtDNA levels remain poorly understood. Understanding this process is crucial as altered mtDNA levels are associated with various human diseases, including rare inherited primary mitochondrial disorders and common age-related diseases such as neurodegeneration and cancer. Additionally, because mtDNA is continuously replicated, it is particularly prone to mutations. This results in heteroplasmy, a condition where both wild-type and mutant mtDNA coexist within the same cell. Some mutations are pathogenic and can disrupt mitochondrial function, causing mitochondrial diseases. However, how cells detect the presence of mutant mtDNA and prevent its accumulation and detrimental effects remains largely unknown. Based on this, our laboratory aims to address three fundamental questions in the coming years: (1) What mechanisms dictate the mtDNA CN of each individual cell? (2) How do cells detect the presence of damaged or mutant mtDNA molecules? and (3) What cellular adaptations result from altered mtDNA homeostasis, and how do maladaptations contribute to disease pathophysiology? To tackle these questions, we will employ a multidisciplinary approach combining high-resolution microscopy, genomics, and high-throughput screening coupled with a wide range of biochemical techniques to measure mitochondrial function. We will use both cellular and novel pre-clinical models of mitochondrial diseases, with the ultimate goal of identifying new therapeutic strategies for patients suffering from mitochondrial dysfunction. **Whom** would we like to hire?** **Professional experience** **Must Have** - Experience in any aspect of molecular or cellular biology - Enthusiastic about science and discovery, with a keen willingness to learn **Desirable but not required/ Nice to have** - Previous experience with microscopy or other cell-biology techniques (tissue culture, qPCR, immunoblot, etc) - Experience in some aspect of mitochondrial research **Education and training** - MSc in Molecular Biosciences (or related). - BSc in Biology, Biotechnology, or any research-oriented degree **Languages** - Fluency in English - Spanish is a plus **Technical skills** - Familiarity with cell and molecular biology techniques - Advanced MS office skills **Competences** - Strong analytical, interpersonal, and communication skills - Curiosity, initiative and critical thinking **The Offer** - Working Conditions** - **Contract d**uration**: 6 months (extendable for other 6 months) - **Estimated annual gross salary**: Salary is commensurate with qualifications and consistent with our pay scales - **Target s**tart date**: As soon as possible We provide a highly stimulating environment