Barth syndrome (BTHS) is a rare genetic disorder caused by mutations in the TAFAZZIN gene, which lead to abnormalities in the protein tafazzin and the crucial mitochondrial membrane lipid called cardiolipin. This leads to a spectrum of issues including impaired muscle function, cardiac irregularities, and susceptibility to infections, significantly affecting the quality of life for individuals affected with BTHS. Our research addresses two fundamental aspects of BTHS research. Firstly, we aim to improve the accessibility to critical data provided by the Tafazzin Human Variants Database by integrating it into other widely used databases. With this, we aim to encourage and simplify future research efforts and collaborations in the study of BTHS. Secondly, we aim to interrogate the molecular consequences of specific TAZ mutations through bioinformatic analyses. Our approach involves mapping these variants with specific segments of the tafazzin protein they affect, to gain knowledge of potential molecular mechanisms of tafazzin function. By examining the three-dimensional structure of the tafazzin protein with pathogenic mutations, we aim to simulate how these mutations impact its function. With deeper understanding of these disease mechanisms, we hope to help in the development of more effective strategies in the search for a cure. Our methodology involves a combination of manual curation, automated data analysis, and molecular dynamics simulations. By addressing these critical research objectives, we aspire to contribute to the advancement of novel treatment approaches and improve outcomes for individuals affected by BTHS.
About the Investigator:
Irma Markesina is a PhD student of Medicinal Chemistry at the Faculty of Biotechnology and Drug Development, University of Rijeka. Irma received her MSc in Biotechnology in Medicine at the same faculty, where she studied the implications of Tafazzin variants in Barth syndrome as part of her master's thesis. During her graduate studies, she worked as a scientific curator where she gained experience in navigating databases and scientific literature. Simultaneously, she volunteered at one of the faculty's laboratories where she studied mutants of Barth syndrome models in the yeast Saccharomyces cerevisiae. She has specialized knowledge in bioinformatics, which is reflected in her thesis that focused on bioinformatics methods. As her PhD study advances, Irma continues to research Barth syndrome through molecular modeling and molecular dynamics simulations.
