Using proteomics to diagnose mitochondrial disease

Bio21 Molecular Science and Biotechnology Institute
Primary Supervisor Email Number Webpage
Prof David Stroud

Summary The Stroud lab uses advanced systems biology techniques to understand the assembly and function of multi-subunit complexes and how their dysfunction underpins a number of important human diseases. We employ a range of mass-spectrometry techniques, including shotgun proteomics, affinity enrichment and BioID proximity studies, metabolic labelling and multi-omics approaches and combine them with patient derived cell lines, CRISPR/Cas9 gene editing, and classical biochemistry. Our research is aimed at both understanding the primary biology underpinning human disease, as well as developing systems biology tools to improve patient diagnostic outcomes.

Project Details

Genetic disorders affecting mitochondrial energy production constitute the most common form of inherited metabolic disease, affecting ~1/5000 births. The diagnosis rate for mitochondrial disease is only ~60%. While whole genome sequencing is routinely applied to patients with suspected mitochondrial disease, sorting through the sheer number of different genomic variants detected in each individual means that for many patients a molecular diagnosis takes months or years. Our lab is developing the use of quantitative proteomics to rapidly prioritise variants of unknown function while simultaneously providing functional validation of their impact on mitochondrial metabolism.

With our collaborators we have now used proteomics to assist in the diagnosis of more than 10 patients with suspected mitochondrial disease (see Lake et al., 2017 Am. J. Hum. Genet. and Frazier et al., 2020 Med as examples). We are now focused on further developing the technique for routine use in diagnosis. This project will utilise quantitative proteomics on patient cell lines, system biology analyses. The project will involve development and optimisation of proteomics sample preparation techniques, as well as the use of CRISPR/Cas9 to validate candidate disease genes. You will also become skilled in molecular cloning, protein biochemistry and human cell culture techniques.

School Research Themes

Cell Signalling

Key Contact

For further information about this research, please contact a supervisor.

Research Node

Bio21 Molecular Science and Biotechnology Institute

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