ESR 4 – Serhii Chornyi, Academic Medical Centre, Amsterdam 

Academic Medical Centre at the University of Amsterdam

Supervisor: Hans Waterham

I received my bachelor and master degree in Ivan Franko National University of Lviv, Ukraine. During my study I worked under the guidance of Oleh Stasyk in the Institute of Cell Biology of Ukraine and Biocenter of Innsbruck Medical University (Austria) in the group of Lukas Huber. In both my projects the main focus was metabolic therapy based on single amino acid arginine deprivation for colon cancer. One of the hallmarks of some types of cancers is their auxotrophic for certain amino acids, for instance, arginine. This inferiority was used to design selective anticancer enzyme therapy. However, the molecular mechanisms of cell response to arginine deficiency are not clear and there is a lot of subsequent possibilities of improvement of therapy efficiency. The goal of my projects was to find the possible relationship of mTORC1 activation in different colorectal carcinoma cell lines and their sensitivity to a single amino acid arginine deprivation. Work in this project sparked my interest in cell biology and brought me into the world of peroxisome research.

Project Title: Human peroxisomal metabolite/cofactor transporter proteins

Peroxisome are single-membrane bounded organelle that present in most eukaryotic cells and responsible for beta-oxidation of very long chain fatty acids, alpha-oxidation of branched chain fatty acids, reactive oxygen metabolism, glyoxylate detoxification and synthesis of ether- phospholipids as well as bile acids. Membrane-bound nature of peroxisome raises the question of how the transport of all metabolites and cofactors across the peroxisomal membrane is accomplished. It is widely accepted that the peroxisomal membrane is impermeable to ‘bulky’ molecules like NAD+/NADH, NADP+/NADH, CoA, ATP. In contrast to plant and yeast, the mechanism of mammalian transport of many cofactors across the peroxisomal membrane is still an enigma. With the application of FRET-based indicators and metabolomic assays, we are going to study peroxisomal proteins that could function as transporters of cofactors and fill the gap in our understanding of human peroxisome functioning. Using CRISPR technology and beta-oxidation enzyme assay we will also characterize generated knock out cell lines to validate the impact of loss of potential peroxisomal transporters on metabolism and peroxisomal functions. Close relation with real clinical practice is also one of the main characteristic features of our laboratory, so we hope that a better understanding of peroxisomal cofactor transport will open new opportunities to improve treatment of patients with peroxisomal metabolic disorders.

My main research interests now lie in the membrane transport and human peroxisomal metabolism.

My free time I love to spend close to nature, I like going to some wild places, living in the tent and enjoy the starry sky and open fire. Since I moved to Amsterdam I’m also spending a big part of my time on cycling. With or without a real destination to aim cycling is freedom and such fun.

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grant number 812968