David Stroud laboratory
A/Prof David Stroud
+ 61 3 834 47316
View A/Prof Stroud's latest PubMed publications listing here
View A/Prof Stroud's latest ORCiD publications listing here
Research in the Stroud laboratory aims to raise the diagnostic rate for monogenic rare diseases, including mitochondrial disease, understand rare disease pathology, and ultimately improve human health through the application new mass- spectrometry based technologies to functional genomics.
We work within 3 primary research themes:
i. Mass-spectrometry based functional testing for monogenic rare disease.
We aim to increase the diagnostic yield for monogenic (caused by mutations in one gene) rare disease through the development and translation of new mass-spectrometry based tests. The key issue in diagnosis of rare diseases is the extreme genetic heterogeneity that underpins the >7,000 rare diseases. Although individually rare, as a group, rare diseases collectively impact ~8% of Australians (see: http://rarevoices.org.au/). Importantly, most rare diseases are subject to the same diagnostic challenges. Currently, the diagnostic workup for most suspected rare diseases involves a first round of genomic sequencing. Genomic sequencing has transformed rare disease diagnosis, raising the diagnostic yield to about 60%. Despite this impressive outcome, up to half of patients remain undiagnosed, and those that do receive a diagnosis often wait months to years. The key challenge in increasing diagnostic yield is confirming which of the hundreds of variants (mutations) detected through genome sequencing are pathogenic. This can be a time consuming and costly process as it often requires development of biochemical tests for each gene. We have leveraged the next generation of mass-spectrometry and proteomics technologies to pioneer a new functional test suitable for many types of monogenic rare diseases, including mitochondrial disease. Proteomics is capable of ‘sequencing’ all proteins (the products of genes) in a single test, making it broadly applicable to confirming which of the variants detected in clinical genome sequencing are pathogenic. To date we have used this new technology to assist in the molecular diagnosis of >30 individuals with confirmed rare monogenic disease. Our current work is focused on standardising and benchmarking our approach with view toward its development as a NATA/RCPA accredited genetic pathology test.
Research on diagnostic proteomics in the Stroud lab is supported by the Mito Foundation
ii. Developing gene-edited cell-based models to understand rare disease pathology.
Functional studies in cell-based models are critical for confirming the pathogenicity of novel variants and the involvement of novel disease genes in disease pathology. In this research theme, we are coupling proteomics-based approaches with gene-edited (CRISPR/Cas9) cell-based model systems to understand rare disease pathogenesis, with a focus on defects in multi-protein complexes relevant to mitochondrial disease, but also investigating other complexes with human disease relevance. Much of the work overlaps with the above diagnostic studies and comprises follow-up studies where novel disease genes are functionalised, while other projects in this theme are aimed at understanding fundamental concepts with relevance to rare disease.
iii. Understanding mitochondrial function through systems biology and multi-omics.
This research theme aims to build on the mass-spectrometry method development of the above themes and combining it with transcriptomics (RNAseq), lipidomics and metabolomics to gain a better clearer understanding of the role mitochondria play in disease pathogenesis and potentially develop new methods to aid rare disease diagnosis.
Dr Daniella Hock, Postdoctoral researcher
Dr Nikeisha Caruana, Postdoctoral researcher
Dr Tanavi Sharma, Postdoctoral researcher
Karena Last, Lab manager
Linden Muellner-Wong, PhD student
Roopasingam Kugapreethan, PhD student
David Robinson, PhD student
Liana Semcesen, PhD student
Minhao Yang, Honours student
Prof David Thorburn, Murdoch Children's Research Institute
Prof Mike Ryan, Monash University
Prof John Christodoulou, Murdoch Children's Research Institute
Dr Diana Stojanovski, University of Melbourne
A/Prof Lena Ho, Duke-NUS
Prof Dany Hatters, University of Melbourne
Prof Brett Collins, University of Queensland
Prof David Bishop, Victoria University
View A/Prof Stroud's recent awards here.
This research project is available to PhD students, Honours students, Master of Biomedical Science, Post Doctor Researchers to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.
See below for a list of key publications from the lab.
- Stroud DA, Surgenor EE, Formosa LE, Reljic B, Frazier A, Dibley MG, Osellame LD, Stait T, Beilharz TH, Thorburn DR, Salim A and Ryan MT (2016) Accessory subunits are integral for assembly and function of human mitochondrial complex I. Nature 538: 123–126. https://doi.org/10.1038/nature19754
- Hock DH, Reljic B, Ang CS, Muellner-Wong L, Mountford HS, Compton AG, Ryan MT, Thorburn DR, Stroud DA (2020) HIGD2A is Required for Assembly of the COX3 Module of Human Mitochondrial Complex IV. Mol. Cell Proteomics 19: 1145-1160. https://doi.org/10.1074/mcp.ra120.002076
- Granata C, Caruana NJ, Botella J, Jamnick NA, Huynh K, Kuang J, Janssen HA, Reljic B, Mellett NA, Laskowski A, Stait TL, Frazier AE, Coughlan MT, Meikle PJ, Thorburn DR, Stroud DA, Bishop DJ (2021) High-intensity training induces non-stoichiometric changes in the mitochondrial proteome of human skeletal muscle without reorganisation of respiratory chain content. Nat. Commun. 12, 1-18. https://doi.org/10.1038/s41467-021-27153-3
- Robinson DRL, Hock DH, Muellner-Wong L, Kugapreethan R, Reljic B, Surgenor EE, Rodrigues CHM, Caruana NJ, Stroud DA (2022) Applying Sodium Carbonate Extraction Mass Spectrometry to Investigate Defects in the Mitochondrial Respiratory Chain. Front. Cell Dev. Biol. 10:786268. https://doi.org/10.3389/fcell.2022.786268
- Amarasekera SSC, Hock DH, Lake NJ, Calvo SE, Grønborg SW, Krzesinski EI, Amor DJ, Fahey MC, Simons C, Wibrand F, Mootha VK, Lek M, Lunke S, Stark Z, Østergaard E, Christodoulou J, Thorburn DR, Stroud DA, Compton AG. Multi-omics identifies large mitoribosomal subunit instability caused by pathogenic MRPL39 variants as a cause of pediatric onset mitochondrial disease. Hum Mol Genet. 2023 Jul 20;32(15):2441-2454. https://doi.org/10.1093/hmg/ddad069 PMID: 37133451; PMCID: PMC10360397.
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