A group of children laughing in the grass

Eight Murdoch Children’s Research Institute-led projects, from unlocking the causes of autism to improving brain cancer treatments, have received National Health and Medical Research Council (NHMRC) grants.

Professor Andrew Sinclair, Associate Professor Silvia Velasco, Dr Ken Pang, Dr Gabrielle Haeusler, Dr Sean Humphrey, Dr Ghazaleh Dashti, Dr Jeremy Anderson and Professor Sharon Goldfeld have each received a share of $12.4 million under the Investigator Grants scheme, designed to support Australia’s highest-performing researchers.

Their research will determine genetic drivers behind Differences of Sex Development (DSD), explore the biology of autism, optimise the use of hormonal treatments for transgender youth, aim to reduce the burden of infection in children with cancer, find new treatments for childhood brain cancer, develop better statistical methods to improve health, visualise the immune functions of preterm babies and address childhood developmental inequities.

The genes behind early sex development

Differences of Sex Development (DSD) are complex genetic conditions where sexual development is atypical, occurring in about 1.7 per cent of births. Professor Andrew Sinclair’s project will work to determine the genetic drivers behind these differences.

The research will identify the genes that are responsible for testis and ovary development and how they can be altered to cause DSD.

“DSD are mainly caused by problems with the genes that control how testes and ovaries develop, but only around 40 per cent of patients receive a formal genetic diagnosis,” Professor Sinclair said.

“My research will identify which genes may be associated with DSD, establish if there are additional cancer risks or reproductive impacts and find better ways to provide earlier diagnosis and appropriate care.”

The biology of autism

Associate Professor Silvia Velasco will investigate the biological causes of autism spectrum disorder (ASD), utilising ‘brain organoids’ created in the lab from human stem cells.

“Brain organoids are a powerful tool to investigate how brain cells develop and understand how alterations during this process can lead to neurodevelopmental differences,” she said.

“We will generate organoids that model different regions, features and functions of the human brain and ultimately uncover the molecular and cellular mechanisms behind complex brain disorders.

“Understanding these mechanisms is fundamental to identify new and effective therapies for neurodevelopmental disorders.”

Optimising hormonal treatments for transgender youth

Dr Ken Pang will undertake research that will answer important questions about affirmative therapy for transgender adolescents.

“Referrals to specialist paediatric gender services have increased substantially across the western world and more data in this area is vital to optimally support these young people and their families,” he said.

“We know that psychosocial support and hormonal interventions are lifesaving for many young trans people and this research will help us offer the most appropriate treatments for those that have reached puberty.”

Dr Pang said his vision was to improve the physical and mental health of transgender adolescents by ensuring the use of puberty blockers were as safe and effective as possible.

“We will investigate whether treatment is best to deliver in early or late puberty and whether this treatment has any impact on cognitive development so young people and their families can make the best possible decisions,” he said.

This project will also undertake an economic analysis that weighs up the  costs and benefits of providing puberty blockers to trans adolescents.

Reducing the burden of infection for children with cancer

Infection-related research gaps in childhood cancer will be investigated by Dr Gabriella Haeusler, Clinician Scientist Fellow at MCRI and Infectious Diseases Physician and Peter MacCallum Cancer Centre’s National Centre for Infections.

“Children with cancer who go through chemotherapy-induced immune suppression can develop serious infections that are often challenging to prevent and to diagnose,” she said. Even though treatments for cancer have advanced, our approach to treating infection has remained the same for many years.”

“We urgently need to offer a more personalised approach to the infection management in this vulnerable population.”

Dr Haeusler’s research program will explore new ways to detect and monitor complicated infections, assess the safety of shortening antibiotic courses and develop national guidelines for infection management to improve outcomes of childhood cancer.

“My vision is to eliminate the burden of infection in children undergoing cancer treatment,” she said. We will achieve this by using innovative research methods, such as trials into electronic medical records and planning pathways for implementation of results into practice.”

Finding new treatments for childhood brain cancer

Dr Sean Humphrey will also work to improve treatments for children with cancer, with a focus on medulloblastoma.

“Medulloblastoma is the most common malignant brain cancer in children and there is an urgent need for more effective and safer treatment options,” he said.

“My team and I will work with The Royal Children’s Hospital to identify any obvious vulnerabilities in this kind of brain cancer by honing in on the communication of these cells.”

Dr Humphrey said findings from this research could be leveraged to potentially develop new therapies for children with brain cancer.

“This work will utilise world-class equipment, mass spectrometry instrumentation, that we have recently installed at the Murdoch Children’s Research Institute,” he said.

“These cutting-edge capabilities were funded by generous philanthropic donations and we are excited to put them to work towards this critical brain cancer research project.”

Developing better statistical methods to improve health

Dr Ghazaleh Dashti’s research will develop new statistical methods to study the causes of diseases and potentially transform the way longitudinal cohorts are used.

“Long-term longitudinal studies use data from the same cohort of people across their lifetime and are powerful tools for understanding how certain diseases occur, but there are critical gaps in how we analyse them,” she said.

“This new research program will develop new statistical methods that can help us understand how diseases occur, and how to treat or prevent them at different life stages with a focus on mental health disorders and cancer.”

Dr Dashti said that by preventing inappropriate analysis in longitudinal research her team could advance our understanding of what treatments harm or benefit people.

“We ultimately want to prevent wrong findings, wasted research efforts or other statistical issues that can derail this valuable long-term research,” she said.

“We will use these advanced analytic methods to generate new knowledge for improving health outcomes across life that will inform policy and practice here in Australia and around the world.”

Visualising the immune functions of preterm babies

Dr Jeremy Anderson will investigate the immature immune system in preterm babies and establish how susceptible they are to severe Respiratory Syncytial Virus (RSV) disease.

“Preterm babies have very underdeveloped immune systems and often do not cope well with infections, especially severe RSV disease,” he said.

This study will characterise immune ‘signatures’ of infants that are hospitalised with severe RSV disease at The Royal Children’s Hospital between 2024 and 2026.

Dr Anderson said that the study would also use ‘fluorescently-labelled’ RSV to determine how the virus infects different parts of a preterm infant’s immune system. 

“This powerful visualisation will show how RSV behaves in stem cells derived from donated umbilical cord blood – and potentially help us to develop more targeted and effective strategies to reduce the burden of disease in this highly vulnerable group,” he said.

Addressing childhood developmental inequities

Professor Sharon Goldfeld will work to drive major reforms in Australia’s health and support services through  child health equity-based research.

This five-year program of research will build on Professor Goldfeld’s previous work with an aim to directly influence current policy and practice.

“By the time many disadvantaged Australian children start school, we see clear inequities in their health and developmental outcomes. This is a serious and possibly preventable public health issue,” Professor Goldfeld said.

“This research will work towards significant, structural and national change, starting with key projects in data analysis, translational trials and the creation of key enablers that work within our current systems and structures.”

Professor Goldfeld’s research will also put emphasis on early interventions, with the ultimate aim to prevent higher rates of physical, social, and cognitive setbacks among children from disadvantaged backgrounds. 

“This research will be anchored within existing and new platforms to get the highest impact at the widest possible scale across Australia,” she said.

These NHMRC Investigator Grants support high-performing researchers at all career stages and helps them broaden the reach and depth of their chosen project.

This significant program also allows recipients to investigate important new research directions as they arise, providing resources for potential additional collaborations.

*The content of this communication is the sole responsibility of Murdoch Children’s Research Institute and does not reflect the views of the NHMRC.