Borko Amulic, PhD, Lecturer (Assistant Professor), University of Bristol, Bristol, UK
“Neutrophil dysfunction in Barth syndrome”
Award: US $49,967 over 2-year period
*Partial funding for this award was provided by Barth Syndrome Trust
Barth syndrome (BTHS) is an X-linked genetic disease caused by loss-of-function mutations in the tafazzin (TAZ) gene, leading to mitochondrial dysfunction and neutropenia, cardioskeletal myopathy and growth delay. Neutropenia is found in 80% of BTHS patients and is accompanied by a risk of life-threatening bacterial infections. The molecular mechanism underlying neutropenia in BTHS has not been fully elucidated. We will examine neutrophils from patients under the care of the UK NHS Barth Syndrome Service to test the hypotheses that mitochondrial defects lead to breakdown of neutrophil homeostasis and impaired antimicrobial function. Specifically, we will analyse (1) metabolism, (2) a neutrophil-specific cell death pathway called NETosis and (3) anti-microbial effector functions, in order to gain insight into disease mechanisms leading to neutrophil dysfunction.