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  • Creating the Future

    The Hector Fellow Academy initiates innovative research projects on latest scientific problems.

From mitochondrial genotypes to phenotypes with single-cell multi-omics

Pauline Kautz – Hector RCD Awardee Leif Ludwig

Somatic mitochondrial DNA (mtDNA) mutations are associated with a wide range of human disorders, yet it has been difficult to reliably establish mitochondrial genotype-phenotype associations. Therefore, we aim to integrate metabolic profiling readouts with single-cell multi-omics sequencing techniques to characterise the consequences of pathogenic mtDNA mutations and increased mitochondrial mutational burden at the cellular and genomic level.

Mitochondria carry their own multi-copy genome and are central to cellular metabolic processes. Germline inherited mutations in mitochondrial DNA (mtDNA) have been associated with different metabolic disorders characterised by a wide variety of phenotypes (known as mitochondriopathies). Likewise, somatic mtDNA mutations accumulate with age and this increased mutational burden can lead to age-related mitochondrial dysfunction. While it is well appreciated that mutations in mtDNA can impact cellular metabolism, the mechanisms of molecular adaptation are less well understood and may further be cell-type specific. Therefore, we aim to integrate metabolic profiling readouts with single-cell multi-omics sequencing techniques to characterise the consequences of mtDNA mutations on cellular metabolism and gene regulation. We envision these efforts to significantly aid our understanding of altered cellular states due to mtDNA mutation related dysfunction that has been broadly implicated to affect cellular function in for example cancer and ageing contexts.

Linking mitochondrial genotypes to phenotypes using single-cell multi-omics sequencing.
Integration of metabolic profiling readouts with single-cell multi-omics sequencing techniques to
characterise the consequences of pathogenic mtDNA mutations and increased mitochondrial
mutational burden at the cellular and genomic level. Healthy mitochondria shown in blue and
mitochondria with increased mtDNA mutation associated burden shown in red.