A new step to identify biomarkers and therapies for Diamond Blackfan Anaemia and other ribosomopathies

Share this:
Share on twitter
Share on linkedin
Share on email

New research supported by Phenomics Australia unravels the molecular mechanisms underlying a group of rare diseases characterised by abnormal ribosome protein production. This work has been published in Cell Reports by researchers at the Australian National University and Peter MacCallum Cancer Centre.

Phenomics Australia Functional Genomics and High-Throughput Screening services nodes at the ANU Centre for Therapeutic Discovery (ACTD), and at the Victorian Centre for Functional Genomics (VCFG), have collaborated to unravel the molecular pathogenesis of a rare class of syndromes called ribosomopathies, which impact on ribosome function and protein synthesis. These include Diamond Blackfan Anaemia, an inherited blood disorder that affects the ability of the bone marrow to produce red blood cells.

Dr Amee George, head of the ANU Centre for Therapeutic Discovery, a Phenomics Australia node at the John Curtin School of Medical Research at the Australian National University, and lead of the research said

“This paper describes our work to unravel the molecular mechanism underlying the nucleolar surveillance pathway, which is a stress response pathway activated when ribosome biogenesis is perturbed. Using high-throughput genome-wide functional RNAi screening conducted in both the ACTD and VCFG, we identified the critical genes involved in the regulation of p53, a tumour suppressor protein which is stabilised when the nucleolar surveillance response is activated. This process underlies the molecular pathogenesis of a rare class of syndromes called ribosomopathies which impact on ribosome biogenesis and ribosome function, including Diamond Blackfan Anaemia.”

“Through genome-wide RNAi screening, we unbiasedly identified that genes which are associated with the ribosome, when disrupted, most potently stabilise p53. Furthermore, we present data to support the notion that a functional nucleolar surveillance pathway is essential for all nuclear-acting stresses to stabilise p53, thus ensuring that ribosome biogenesis is hardwired to cellular proliferative capacity through p53 activity”.

“Our data provides important information that will help us in the future to identify biomarkers and therapies for Diamond Blackfan Anaemia and other ribosomopathies, as well as develop new cancer therapies which selectively activate the nucleolar surveillance pathway.”

This manuscript is dedicated to the memory of A/Prof Kate Hannan, Head of the Cancer Therapeutics Laboratory in the Division of Genome Sciences and Cancer in the John Curtin School of Medical Research, whose contribution was key to the publication of this work.

Phenomics Australia Feedback Form

Phenomics Australia (formerly the Australian Phenomics Network, APN) offers consolidated infrastructure and expertise supporting genomic medicine and biomedical research from discovery through into early clinical development and evaluation.

Phenomics Australia is a founding capability enabled by the National Collaborative Research Infrastructure Strategy (NCRIS). We would love to hear from you!

Please feel free to provide any ideas or general comments you might have so that we can further improve how Phenomics Australia can support you.

Phenomics Australia PHENOMENA News Contribution

Have you recently had a publication accepted? Do you want to tell us about a grant you have received? Or maybe you have just been recently in the news? You can complete this form to tell us about your latest research developments.

Information provided will be used to inform press releases, website stories, social media content and more. This form is being used to capture everything that is happening at Phenomics Australia, which can then be used as part of our outreach and communications.

Once you have completed the form, the Communications and Outreach Coordinator will then be in contact with you.

Thanks.

Make an Enquiry

_Get in touch to discuss how we can help with your research.