Exploration of novel biomarkers of biliary atresia in neonatal dried blood spots

Biliary Atresia [BA] is a rare, inflammatory pathology occurring in newborn infants which causes necrosis of the bile duct. Early diagnosis is important as effective intervention is time-critical. In New Zealand, diagnosis is often delayed leading to inferior outcomes for affected infants. NZ has more than double the rate of BA compared with America and Europe due to elevated incidence in infants of Maori and Pacific Island descent. Lack of a clear clinical phenotype leads to a delay in diagnosis with resulting poor clinical outcomes (liver transplant and or death).

New Born screening Guthrie cards trap a drop of a neonate’s blood collected in the 48 hours postpartum. There are a number of metabolites detectable in blood which discriminate BA from unaffected infants. None currently achieve the sensitivity and specificity required for standalone community screening. Conjugated bilirubin is the closest but has not been investigated in Guthrie cards due to concerns of photolability. Mass spectrometric analysis of BA Guthrie cards show differing patterns of changes compared to controls, but still lack specificity.

In this project we will conduct laboratory experiments with dried blood spots spiked with conjugated bilirubin and stored under different conditions. Using Liquid Chromatography with Mass Spectrometry [LC-MS] we will quantify relative changes in the abundance of the blood spot metabolome to characterise it’s stability and degradation. We will use multivariate statistics to identify which metabolites are correlated with the change in conjugated bilirubin to identify proxy biomarkers that will allow us to predict its original concentration. We will then carry out follow-up with analysis of blood spots collected on Guthrie cards of infants with BA, neonatal cholestasis and normal controls to quantify those biomarkers and evaluate our ability to classify the samples.

• Applicants should have a good grasp of the biochemistry, physiology and metabolism of animals. Experience with quantitative analytical techniques such as pipetting, spectrophotometry, preparation of standards, chromatography and mass spectrometry, will be highly favourable.
• This would ideally suit students already enrolled in an MSc at the University of Auckland in the field of Biomedical Science, Chemistry, Health Science or Med Lab Science, looking for a 90 or 120-point research project.

Limited scholarships or philanthropic funding may be available periodically.

Closing date: Wednesday, 30 April 2025