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Professor Jürg Bähler
University College London
International Academic Fellowship
2018

Learning about ageing from a short-lived fish

Adult male (left) and female (right) turquoise killifish in a research facility. Picture by Giovanni Stefani, University of Trento.

As a geneticist, I have worked with yeast as a simple model system throughout my career. We are investigating genome function and regulation, including factors affecting the ageing and lifespan of cells. Ageing is a fascinating biological process which affects us all sooner or later. Although single-celled yeasts have been useful to identify basic principles of ageing, they are limited to understand the more complex, multi-factorial processes associated with ageing in multicellular organisms like humans. I am therefore keen to also establish a tractable animal model organism in my laboratory to enable complementary, advanced insights into the nature of ageing. 

A midlife crisis perhaps, but I have recently become intrigued by the African turquoise killifish, Nothobranchius furzeri, which emerges as a potent model system for ageing. This fish inhabits seasonal ponds in Southeast Africa. It therefore grows, reproduces and ages very rapidly during the short rainy season. Older fish show multiple hallmarks of ageing typical for humans, such as reduced muscles and frequent cancers. The fish only lives for about 5 months. Its eggs then survive the long dry season in diapause, a state of suspended animation. Diapause features delayed ageing, and likely shares genetic mechanisms with longevity. Killifish has tremendous potential as a new model organism. Its genetic tractability and short adult lifespan allow rapid, cost-effective assays to study ageing and associated biological processes. 

I will spend my Fellowship at Stanford University (Palo Alto, USA), with the group of Professor Anne Brunet who are pioneering ageing experiments with killifish. This stay will allow me to learn about the general husbandry and breeding of killifish. Such know-how will be critical to adopt standardised conditions for reproducible experiments at UCL. The Brunet laboratory is at the forefront of killifish research, and I will also learn specialised techniques like genome editing to generate fish with specific mutants. For example, such mutants could make the fish live longer. The broad, direct experience with both routine upkeep methods as well as cutting-edge genetic approaches will equip me with a strong basis to train group members in essential procedures to successfully establish the killifish model back in my group in London. Moreover, Stanford’s Genetics Department includes many groups pursuing a wide range of research on molecules, organisms, populations and genomes. Without doubt, exposure to this varied, rich science will generate fresh ideas for my own research and opportunities for future collaborations. 

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