Hong Kong — The zebrafish has been utilised as a model organism for biomedical research globally for half a century, mainly due to the high genetic similarity (over 70%) between zebrafish and human genes, with over 80% of human morbid genes related to at least one zebrafish orthologue.

As test subjects, zebrafish are suitable for high throughput applications (to screen a large amount of genetic data simultaneously) and are widely used as a model organism for studying vertebrate development and for characterising diseases such as cancer, to help in identifying and testing new drugs. Fast development, cost-effective and easy to breed are also primary drivers for using the zebrafish research model. However, a recent research project led by Dr Alvin MA Chun-hang, Assistant Professor of the Department of Health Technology and Informatics, The Hong Kong Polytechnic University (PolyU), has revealed that the conventional application of 1-phenyl 2-thiourea (PTU), a pigment suppresser used in the zebrafish research model, may affect the results of autophagy-related studies.

This ground-breaking finding subsequently sheds light on the respective research guidelines and the research protocol in on-going studies on autophagy and haematology, warranting researchers to re-examine research that is linked to existing cancer therapy options. The research titled “1-phenyl 2-thiourea (PTU) Activates Autophagy in Zebrafish Embryos” (link) was published in Autophagy, a peer-reviewed science journal in April 2020.

Photo – https://mma.prnewswire.com/media/1212533/Photo1.jpg

In most research using the zebrafish model, a chemical compound called 1-phenyl-2-thiourea (PTU) is commonly used to suppress pigment formation in zebrafish embryos, maintaining optical transparency to facilitate microscopic imaging.

Over the past three years, the PolyU research team led by Dr MA has been using the zebrafish model to investigate the causes of leukaemia and its relationship with autophagy (self-eating) – a mechanism of metabolism that involves the degradation of cells by lysosomes and the process of cell renewal and regeneration. It is a cellular reaction to various physiological and pathological conditions regulating important processes, including intracellular material turnover, cell death, proliferation, development, ageing and tumourigenesis.

According to Dr Ma, “Upon 0.003% PTU treatment, aberrant autophagosome and autolysosome formation, accumulation of lysosomes and elevated autophagic flux were observed in various tissues and organs of the zebrafish,” He pointed out that “Autophagy is crucial in the process of drug resistance of various cells and over-activation of autophagy may potentially interfere with the efficacy of drugs.