The Wesfarmers Centre is pleased to announce the successful applications for the 2016 Round 2 Wesfarmers Centre Seed Funding.
The Wesfarmers Centre Scientific Committee collectively scored each grant using the NHMRC project grant criteria, and awarded funds only where it was confident it would lead to a highly competitive grant application (weighted score >4.8).
Jenefer Blackwell| Telethon Kids Institute Selma Jeronimo (Federal University of Rio Grande do Norte), Timo Lassmann (Telethon Kids Institute), Denise Anderson (Telethon Kids Institute), Dave Tang (Telethon Kids Institute). Awarded $21,280.00.
Zika: Is there an underlying genetic/epigenetic basis to microcephaly and eye damage due to congenital Zika virus infection?
Microcephaly is usually associated with Mendelian inheritance of rare genetic variants affecting developmental pathways. Clinical application of next generation sequencing has greatly improved ability to identify rare variants associated with developmental anomalies. We now know a lot about genes and mechanisms responsible for brain development, and where perturbations occur that cause congenital microcephaly and severe eye disorders. Our hypothesis is that congenital Zika virus infection dysregulates these genes early in the developing fetus, in a manner similar to what our data suggests is happening in other congenital infections like CMV (microcephaly) and toxoplasmosis (severe ocular disease; brain lesions). We can get a handle on this in two ways: (i) using next generation sequencing that captures regulatory and coding regions of all genes; and (ii) using DNA methylation arrays to determine whether congenital Zika infection has left its mark on the epigenome of infected babies. We will look for enrichment of rare genetic defects in microcephaly/eye disorder genes in Zika babies, and identify the genes that are subject to changes due to epigenetic signatures left by the virus. This proposal is timely as Zika transmision, and associated microcephaly in babies, is now spreading outside of South America, and could be introduced into Australia. Determining developmental pathways perturbed during congenital Zika infection could identify key pathways for drug repurposing, while genetic screening could identify babies at increased risk in mothers infected during pregnancy. The results will have broader implications for other congenitally-acquired infections causing developmental anomalies in babies, including CMV and toxoplasmosis.
Holly Clifford| Telethon Kids Institute Andrew Whiteley (University of Western Australia), Lea-Ann Kirkham (University of Western Australia), Ruth Thornton (University of Western Australia). Awarded $22,922.00.
The dust microbiome: how does it affect susceptibility to bacterial lung infections in Aboriginal Australian children?
Aboriginal children are 10 times more likely to die from lung disease than non-Aboriginal children. Aboriginal children experience many bacterial infections from a young age, and these frequent and long-lasting infections can lead to long-term lung disease as the children grow older. Infectious lung diseases are a major problem for people living in remote communities. There may be unique exposures in the physical environments of the remote regions of the country that make infections worse - this needs further investigation. Exposure to inhaled,earth-derived (or "geogenic") dust is extremely high in remote Aboriginal communities, and it has been shown that dust storms cause more people to be hospitalised with lung infections. We are particularly interested in investigating Australia's distinctive "red dust" - what exactly is in this dust and what are its effects during bacterial lung infections? The "dust microbiome" - or community of microbes within the dust - is likely to have significant effects, however, this has not yet been fully explored.
Once dust is seen as not just a nuisance but as a real threat to lung health, dust levels can be reduced relatively easily in remote Aboriginal communities across Australia by funding interventions to decrease exposure to airborne dust, such as by increasing gardens and sealing roads. We predict that this will lead to improved lung health in the most vulnerable group of Australian children. This research may also have global significance by reducing the burden of lung infections in resource-poor, arid settings worldwide, such as the meningitis belt in Africa.
Hannah Moore| Telethon Kids Institute Chris Blyth (Princess Margaret Hospital for Children), Pia Hardelid (University College London), Tasnim Abdalla (Telethon Kids Insitute). Awarded $19,833.00.
Enhanced paediatric respiratory epidemiology: international comparisons to inform current and future intervention strategies
Acute respiratory infections, or chest infections, including bronchiolitis, pneumonia and influenza are a major health problem responsible for 1.9 million deaths worldwide in young children every year and the leading cause of hospitalisation in children aged <5 years. Infants aged <12 months experience the highest admission rates. There is a disproportionate burden of chest infections in Indigenous and other disadvantaged populations. In Australia, admission rates are >7 times higher in Aboriginal children aged <2 years than in non-Aboriginal children of the same age. The aetiology of chest infections is diverse with many viral and bacterial pathogens implicated. Some are vaccine preventable (e.g. S.pneumoniae, pertussis, influenza), while others have vaccines in late stages of clinical development (e.g. Respiratory Syncytial Virus). Additionally, antibiotics and antivirals are available with others expected to become routinely available in the future.
In order to sensibly inform planning and evaluation of vaccination and treatment strategies, accurate burden of disease estimates and understanding of the relative contribution of specific risk factors (poverty, crowding, smoking), particularly in populations at increased risk, are required. These estimates traditionally rely on hospital discharge coding using a selection of diagnosis codes. Enhancing hospital discharge data with perinatal data and routinely collected laboratory data is possible through population-based data linkage. There are few centres worldwide with the capacity to do this. We have formed a collaboration with the University College London. Both our research groups have the capacity to undertake large-scale population-based data linkage projects using administrative health data. Our ongoing collaboration will enable a greater understanding of the global burden of chest infections in children, particularly populations at greatest risk of disease.
Mejbah Bhuiyan| University of Western Australia Tasnim Abdalla (Telethon Kids Insitute), Tom Snelling (Telethon Kids Institute), Chris Blyth (Telethon Kids Institute), Julie Marsh (Telethon Kids Institute), Hannah Moore (Telethon Kids Institute), Peter Richmond (Telethon Kids Institute). Awarded $4,872.00.
A meta-analysis and meta-regression of the contribution of respiratory viruses to the global burden of community-acquired pneumonia in children
Pneumonia is the greatest cause of death among young children. Approximately 150 million episodes occur annually with nearly 2 million deaths. Pneumonia remains an important public health concern in developed countries with growing resistance of bacteria to antibiotics, identification of new causative pathogens, and bacterial pneumonia caused by replacement non-vaccine strains.
In the past, studies have focused on the role of bacteria. This has led to effective vaccines targeting the major bacterial causes of childhood pneumonia, pneumococcus and Haemophilus influenza type B. With improvements in technology, it is now thought that approximately 80% of childhood pneumonia is caused by respiratory viruses. Despite this, antibiotics are still prescribed to the majority of children. In recent years, a large number of aetiology studies have been conducted across different settings and different age groups. These studies have used varying case definitions and methods for pathogen detection - from blood, nasopharyngeal aspirates or swabs and pleural fluid (for severe cases).
This variation has made it difficult to reconcile differences and distil a comprehensive understanding of the contribution of viruses to childhood pneumonia. To our knowledge, no group has attempted to aggregate the dozens of childhood pneumonia aetiology studies through systematic review and formal meta-analysis.
Given treatment and prevention of childhood pneumonia remains a global health priority, and appropriate preventive strategies such as vaccines are dependent upon understanding which viruses contribute to this burden and by how much, we anticipate such a review will be highly informative for future pneumonia research at WCVID and for researchers and policy-makers internationally.