This study will develop an improved protocol for testing children with intellectual disability (ID) of undefined cause. We expect that in 2,000 children whose ID is not explained by standard testing, we will identify and clinically assess ~160 children that have a small proportion of cells with abnormal function in genes that cause Fragile X syndrome and Chromosome 15 imprinting disorders. Early diagnosis in these children and can improve outcomes through early intervention and informed reproductive choices for their families.

Brain cancer kills more children than any other disease. Children with high grade glioma have 5% survival rate, with no new treatments in decades. Immunotherapy is a powerful new weapon against cancer with impressive clinical benefit. Chimeric antigen receptor (CAR) T cells are genetically engineered killer cells, targeting the tumour. This project characterises various receptor designs to determine which format promotes maximum killing with limited inflammation. This will provide a much-needed new therapy for this aggressive and fatal cancer in children.

Individuals who are born prematurely are known to be at a greater risk of developing heart disease and diabetes as adults than those born at term. This study will determine whether providing preterm infants with a simple nutritional intervention in early infancy, in the form of a high dose omega-3 supplement, can reduce their future risk of heart disease and diabetes.

We were the first to report viral mediated gene editing in the retina, and the application of this technology opens the prospect for anticipatory cures to some inherited retinal diseases. We now seek support to generate substantial pre-clinical data for use in our case submitted to the TGA for a first in human clinical trial for gene-based therapy for PCDH15-related Usher Syndrome. Children affected by this neglected, orphan disease are born deaf and generally become blind during their teenage years.

Our knowledge about the molecular mechanisms that cause genetic bone and cartilage diseases and how these could be manipulated therapeutically remains incomplete. Bone and cartilage cells are not available from patients for study and so we will turn stem cells derived from accessible patient skin cells into cartilage and bone to determine the cellular response to mutant protein and how the mutations cause disease. We will test drugs that target the pathological pathways to provide therapeutic strategies for patients.

Regular consumption of traditionally allergenic foods, like egg and peanut, in solid foods can reduce food allergies, however this is too late for some infants. We have discovered that infant immune responses to egg can be beneficially enhanced during the first six weeks of breastfeeding when mothers eat more eggs. We now propose to investigate the effects of breastfeeding mothers eating higher dietary intakes of both egg and peanut for an extended period of the first six months of life.

Childhood anxiety is common and problematic for many young Australians. Although we have effective treatments, very few young people receive help. We propose new research to translate our knowledge about evidence-based practice into real world solutions that children want to use, that are accessible, are low cost and ultimately, provide the right support to the right children. This study will examine the effectiveness of a stepped-care model for delivering evidence-based treatment for child anxiety via the internet.

Septic shock is a life-threatening condition usually caused by bacterial infection in the bloodstream. More than 5000 people, including 500 children, die from sepsis each year in Australia. Worldwide, it is the most significant cause of death in children. Sepsis is associated with leakage of fluid and proteins through the cells lining the blood vessels. We are developing a novel treatment for sepsis which focuses on reducing this leakage by blocking the Eph/ephrin proteins.