Congratulations to Rhett Marchant who graduated from The University of Sydney with Honours Class I and was awarded The University Medal. The University Medal is awarded to honours students based on outstanding academic performance over their complete student enrolment.

Rhett’s thesis was focussed on improving rare genetic disease diagnosis. During his studies he worked with Professor Sandra Cooper and the Genomic Medicine team at Kids Neuroscience Centre (KNC).

Rhett’s thesis investigated the following two questions.

1. How we can find variants which may cause genetic disease in a family when we think we have looked everywhere?
2. How can we confirm a disease causing variant in the lab if we don’t have access to patient tissue to test?

As part of the Sydney Children’s Hospitals Network the team at KNC are on the ground and able to move swiftly from investigation to treatment. Rhett says,

We are in constant dialogue with clinicians who provide us with ideas and insights on how our findings relate to their patients, and the clinicians are able to learn from our team’s expertise in the genetic mechanisms underlying disease and better understand the analysis that we conduct to evaluate genetic variants.

For many families, the variant causing genetic disease may remain elusive even after whole exome sequencing and whole genome sequencing. In his investigation, Rhett explored five such families with the aim of developing a bioinformatics workflow which could help uncover their disease causing variants. By specifically focussing the workflow to look for RNA splicing variants, Rhett successfully identified a promising variant in a potential new disease gene in one of his families. Since then, the team have been working on functional studies in the lab to explore this new gene and how it may be causing disease.

Rhett also investigated how confirming a disease causing variant in the lab may be possible even without access to patient tissue. He worked on a minigene assay to evaluate a suspicious variant identified in a family with a connective tissue disorder. Minigenes are small, synthetic gene-like molecules which contain part of the gene being studied and they enable the team to explore the effects of different variants on RNA in situations where patient tissue is not available. His work is now in the process of being distributed to the referring clinician and the affected family, who hope to use the findings for guiding treatment.

To conclude his project, Rhett presented his minigene work at the SpliceACORD clinical consortium which allowed the Genomic Medicine team to gain insight into how the genetic pathology community might approach using minigene assay data for diagnosis. This project was part of a larger goal of the team to extend RNA diagnostics to genetic diseases caused by genes only expressed in inaccessible tissues, for example, in the brain, bone, or heart.

Now as a Research Assistant, Rhett is continuing to explore new ways to look for suspicious genetic variants and works collaboratively with scientists and clinicians across Australia and the world to try find genetic answers for undiagnosed families.

Pictured: Rhett presenting his work at the Westmead Precision Medicine Conference 2021