MitoPhenomics Lab

MitoPhenomics of mitochondrial disease.

Mitochondrial diseases (MD) are metabolic disorders of oxidative phosphorylation that affect ~1 in 5,000, cause substantial morbidity and have no cure. The clinical features involve tissues with high-energy demands, especially striated muscle and the nervous system. MD are genetically determined by mutations of mitochondrial DNA (mtDNA) or nuclear genes encoding mitochondrial proteins. mtDNA is a small, circular DNA, that encodes 13 polypeptides of the electron transport chain and the tRNAs and rRNAs necessary for their synthesis. mtDNA is maternally inherited and polyplasmic, each cell and mitochondria contain many copies of mtDNA where several alleles can co-exist in a state called heteroplasmy (ratio WT/mutant). In a state of homoplasmy the cell contains mtDNA of a single genotype. Heteroplasmy occurs when exists a subpopulation of mtDNA by a variance in mtDNA sequence. In heteroplasmic pathological variant the phenotype is thought to need a certain threshold to be disease-causing.  However, a great variation in the penetrance of mtDNA pathogenic mutations have been observed, suggesting a complex interplay between the primary OXPHOS defect and the compensatory adaptation to that dysfunction.

MitoPhenomics lab studies new compensatory mechanisms in cells from patients with MD. Our over-arching aim is to develop new treatments for these diseases using a combination of genomic, cell biology, and bioinformatic techniques on human tissues and cell models. Understanding the molecular mechanism will reveal tissue specific targets and will provide rationale for developing novel therapies.

The student will learn a combination between dry and wet lab. The project will unite basic bioinformatics analysis on pre-existing transcriptomic and metabolomics data with cell biology studies (cell culture, quantitative PCR, Western blot, microscopy, etc). We will also perform some genetics analysis on bulk and single cell (NGS, pyrosequencing, etc). The overall aim is to learn how to characterize new targets in MD. In addition to their own research, there will be opportunities for training and career development.

The main tasks will be:

• Identifying new molecular mechanisms involved in the penetrance of mitochondrial diseases
• Contributing to the design and interpretation of laboratory experiments
• Close working with experimental laboratory scientists
• Presentation at lab meetings
• Writing scientific articles describing key findings.