New technologies informing future approaches to mitochondrial disease

University of Melbourne Postdoctoral Fellow Dr Elena Tucker has achieved a lot in a short amount of time. Inspired by a life-long interest in genetics and the real-life impact of improving human health, Dr Tucker’s research is focused on mitochondrial disease.

Dr Tucker completed her PhD at the Murdoch Children’s Research Institute and the Department of Paediatrics at the University of Melbourne in 2011. Her research used Next Generation Sequencing (NGS) to identify the genetic cause of mitochondrial disease in many patients. Using this NGS technology illustrates how such science is rapidly transforming research and patients’ outcomes in the disease. 

This research has received extensive recognition within the scientific field. However, when you discuss mitochondrial disease and the quest for a cure, it is clear Dr Tucker is not in it for the accolades.

“I’ve always been interested in genetics and passionate about improving human health. If my research can prevent future cases of mitochondrial disease and reduce the suffering of patients and families, then I’m happy,” she says. 

Dr Tucker is motivated by applying her knowledge of genetics to situations of real life impact, where discoveries can help change the course of a patient’s treatment.

“I’ve always loved genetics. But I didn’t want to study genetics just for the sake of knowledge; I wanted some application for what I was doing and an application for people. I’m motivated by hearing the personal stories of the children we are studying and really being able to help those families.” 

It is in this same spirit that has seen Dr Tucker receive widespread recognition for her research into mitochondrial disease. In November 2012, she was awarded an NHMRC Peter Doherty Australian Biomedical Fellowship and also won a Victorian Tall Poppy Award for Science. 

Dr Tucker also received a Commendation in the Premier’s Award for Health and Medical research in 2012. Receiving these awards “…made me feel really happy that my research was recognised and that I really am at the forefront of this research,” she says. 

Mitochondria are present in every cell of the human body and are responsible for generating the majority of energy required for normal bodily functions. When mitochondria do not function properly, mitochondrial disease results. This is a devastating and often fatal condition affecting approximately 1/5000 live births. 

There are already more than 100 known mitochondrial “disease” genes but these genes account for about only half of patients, highlighting that there are many more to be discovered. 

For families without a genetic diagnosis, this discovery process often means ongoing tests and uncertainty about the progression of and treatment for their condition. The research focused on identifying the causes of mitochondrial disease using gene sequencing technology. 

“This diagnostic ordeal continues for patients until a genetic diagnosis is achieved, which often takes years and is sometimes never achieved. My research uses new technology that can speed up genetic diagnosis because thousands of genes can be investigated at once, rather than one by one,” she says.

The use of Next Generation Sequencing technologies has allowed for the scope of such projects to increase, as well as reducing the diagnosis time for patients. The research findings will contribute to improvements in treatment for people with mitochondrial disease.

“Once a genetic diagnosis is achieved, families can better understand and accept the condition and can use genetic testing to ensure future children are not affected. Furthermore, this work has enabled the identification of new “disease genes”, giving new insights into mitochondrial function which hopefully will help the development of treatments and cures, which are currently lacking for this devastating group of diseases,” she explains.

For Dr Tucker, working at the Murdoch Children’s Research Institute under the supervision of Dr Alison Compton and Professor David Thorburn, Acting Director of the Genetic Disorders Theme at MCRI was a great experience.

“My supervisor, David Thorburn has been a fantastic mentor. He has vast knowledge and I’m always impressed by his ideas and insights. He’s been encouraging, supportive and has given me many opportunities that I’m grateful for – to travel to international conferences and laboratories, to write reviews and peer-review manuscripts among other things.”

Professor Thorburn believes Dr Tucker has been a “key player” in some of the first studies applying Massively Parallel Sequencing approaches to patients with genetic diseases.

“Dr Tucker’s research has set a current benchmark for what we know about the genetics of mitochondrial disease…The approaches Dr Tucker has taken are informing the way others will study not just mitochondrial disorders but many other inherited conditions. Importantly, her work has pointed out many issues related to the complexities and subtleties of these approaches.

“Dr Tucker’s approach was to study patients that are more representative of the typical clinical situation where most patients suspected of a genetic disorder do not have a strong family history that helps narrow down the focus,” he says.

Collaboration was also of key importance in this research endeavor. Dr Tucker’s research was part of an international collaboration at the Broad Institute of MIT and Harvard. 

In future, Dr Tucker hopes that gene sequencing technologies will be used ethically for genetic diagnosis in general.

“I hope that they will be able to be used for conditions that are treatable, because if you can get a quick diagnosis for a treatable condition you can really change the clinical course of that patient.”