What is your role?

I was initially hired by the Kids Neuroscience Centre as a research assistant to support the Gene Discovery research team. Our team has a cohort of ~200 families with various neuromuscular disorders who did not previously have a genetic diagnosis. The aim of our team was to find the genetic cause of disease for all these families, with a secondary goal of identifying new genes associated with neuromuscular disorders. DNA from these families was sent to the Broad Institute of MIT and Harvard for massively parallel sequencing. Basically, this provides us with details of detectable genetic variation in a person. Our team analyses this data to determine which genetic variants cause disease.

Finding the correct answer for each family is difficult as each individual is born with thousands of unique variants in their genome which makes finding the specific disease causing variant very tricky. My role within the team is to perform laboratory based experiments to provide extra evidence that a particular variant in a person’s genome is causative of the neuromuscular disorder.  To date our team has found a genetic diagnosis for ~60% of our families.

How did you get in this area of study?

When I finished high school, I didn’t really know what I wanted to do. I liked animals so I decided to do a Bachelor of Science – Zoology at Western Sydney University (2012-2014). This degree had the option of a major so on a whim I chose to do a biochemistry and molecular biology major without really knowing much about these topics. I found the subjects within this major far more interesting and challenging than my other subjects, particularly “Genes, Genomics and Human Health” which explored many different types of genomic changes and how these result in disease. When I finished this degree I had a passion for genetics but predominant knowledge in animal biology.

I decided the best way to further my knowledge and experience in genetics and molecular biology would be to do an honours project. I ended up finding a project at the National Measurement Institute in the bioanalysis team. I completed my project in 2015 working with new technology to detect trace levels of cancer cells in Leukaemia patients to determine the risk of relapse. After receiving first class honours I was able to apply for the research assistant position advertised at the Kids Neuroscience Centre, which landed me in the human genetics field I was so interested in.

In laymen’s terms what area do you do research in?

For my PhD, I am researching genetic variants which impact splicing. Splicing is a process by which the instructions found in your DNA are put together in a way that can be correctly read and interpreted by your cell to make a functional, healthy protein.  Some genetic changes can mess up how these instructions are put together, which can lead to a dysfunctional protein being made or no protein at all!

These genetic variants disrupt the process of splicing. There are programs available which aim to predict if these genetic variants will affect the cells ability to find the correct “pages” of instruction, but these aren’t always accurate. Functional studies are needed to see exactly what “pages” of the instructions are actually being used by the cell, to show that a splice variant is the cause of disease. For my PhD, I have been performing these functional studies to investigate splice variants identified in some of our patients and have shown that these are the cause of disease, providing these families with genetic diagnoses which can help with treatment and family planning.

What does a typical work day look like for you?

I have found that in my work, there is never a “typical” day. There are days where I find myself mostly at my computer searching through patient data, comparing it to what is known in the literature and designing experiments to investigate possible outcomes. There are days where I’m mostly working at my laboratory bench doing experiments that can take hours with lots of little steps to complete. Other days can be mostly filled with meetings as I explain and discuss my results with my team and then to clinical staff that will pass the information on to their patients, translating my work into clinical care for patients and their families.

Briefly explain how the scholarship will assist with your research?

The 2018 MDNSW Sue Connor PhD Scholarship helps me enormously with my PhD as it relieves financial pressure and allows me to focus on my work. It will enable me to continue my research which can be directly applicable and helpful for the families with neuromuscular disorders that we have been studying.

What are the long term goals of the research?

Currently, functional studies to investigate the impact of splice variants are not widely available. This means that many potentially disease causing variants end up being classified as “variants of unknown significance” or VUS. Doctors and families cannot interpret these results and the family remains without a definitive genetic diagnosis. Our laboratory has extensive experience in carrying out these studies. We aim to create robust practical guidelines that can be used by diagnostic laboratories in standard clinical practice.

It isn’t always possible to perform functional studies to determine the effects of a splice variant, as it requires patient tissue which can be invasive to obtain (e.g. muscle biopsies). By understanding how genetic variants can disrupt splicing, our work can inform predictive programs of the future and improve their predictive power, enough to find a diagnosis without these functional studies.

In general, the long term goal of this research aims to equip doctors with more resources and tools to accurately determine if a splice variant is the underlying cause of a genetic disorder. With this knowledge and understanding, fewer variants will be classified as a VUS and more families will benefit from obtaining a genetic diagnosis.

Where do you see yourself in five years’ time?

Advances in the field of genomic medicine are occurring rapidly so it’s very difficult to picture what it will be like in 5 years’ time. I plan to be working on cutting edge translational science bringing genetic analysis to patient care, to improve the rate of genetic diagnoses for families with rare genetic disorders.

Anything else you would like to add?

I absolutely love the work that I do. I gain immense job satisfaction when the work I do directly helps families with neuromuscular disorders. For example, earlier this year I was able to confirm the genetic diagnosis for a couple who desperately wanted another child. They can now use pre-implantation genetic diagnosis (PGD) to ensure that their next child is healthy. Another family that I helped diagnose was able to be treated with a medication known to help with their condition and now they are regaining ambulation, improving their quality of life. Another family has been waiting for more than 10 years for their diagnosis and I was able to put the last piece of the puzzle together, providing them with a diagnosis allowing for family planning. I am honoured to have been given this scholarship and to have the opportunity to continue to help families with neuromuscular disorders.