How our bodies sense and respond to environmental changes are fundamental biological questions. In particular, understanding how organisms sense and cope with warming temperatures is key for the survival of species and it will become an even more important area of research given the raising trend in the earth’s temperature. In research recently published in PLOS Biology, researchers from the Casanueva group used the tiny nematode worm C. elegans to show for the first time that although ectotherms cannot internally regulate their own body temperature as mammals do, they are able to centrally control their response to heat.
Rising temperatures are problematic for cell membranes, which are mostly made of fat molecules called lipids. Lipids are extremely sensitive to temperature change and must be regulated for cell membranes to be able to maintain their function. Multicellular organisms face an additional challenge: membrane lipids are only produced and kept in specialised fat storage tissues. The question is how can distant tissues get the right type of lipids to adapt their membranes in response to temperature change?
Endotherms, such as mammals and birds, maintain their body temperature by using peripheral sensors to relay information to the brain, where specific neurons function as a type of thermostat that sets and maintains a healthy body temperature. By contrast, ectotherms, such as reptiles, fish, and invertebrates, cannot control their own body temperature. For invertebrates like C. elegans, it was thought that this process was controlled independently by individual cells rather than coordinated on an organism wide level.
Dr Olivia Casanueva and her team have shown that in C. elegans a group of neurons in worms act by registering external temperature and coordinating fat remodelling. This process is a result of a conserved response that exists in all animals called the heat shock response. When exposed to heat stress, cells activate the Heat Shock Response pathway during which the signalling molecule Heat Shock Factor 1 (HSF-1) rapidly induces the production of heat shock proteins (HSPs), which are themselves involved in repairing heat-damaged proteins. HSF-1 is also recognised as a pro-longevity factor because it clears aggregates and misfolded proteins that accumulate in old cells.
In this study, Dr Casanueva found that in some sensory neurons, HSF-1 responds to slight changes in temperature and sends signals through a multistep response to the gut, where fats are made. The team took advantage of the transparency of the worm’s cuticle to visualise fat metabolism in individual worms. They found that HSF-1 is necessary and sufficient to coordinate a complex neuro-hormonal response between the neurones detecting temperature change and fat producing gut cells.
“This is the first study to show that ectotherms utilise an ancient heat sensing cellular response as a thermostat to centrally coordinate complex adaptive responses to warming temperatures.” said Dr Casanueva, “This response ensures that the right type of fats are made for membrane remodelling across the organism’s tissues and allows worms to survive warming temperatures.”
By better understanding how invertebrates regulate fat composition in the body, future research will be able to identify if a similar role has been co-opted in mammals, which may be important in the context of ageing and obesity in humans.
Chauve L, Hodge F, Murdoch S, Masoudzadeh F, Mann H-J, Lopez-Clavijo A, et al. (2021) Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans. PLoS Biol 19(11): e3001431.
Honor Pollard, Communications Officer, email@example.com
Image description: C. elegans worms labelled with a fluorescent protein and imaged using a confocal microscope.
Affiliated authors (in author order):
Laetitia Chauve, former postdoc, Casanueva lab
Francesca Hodge, former research assistant, Casanueva lab
Sharlene Murdoch, former senior research assistant, Casanueva lab
Fatemah Masoudzadeh, former visiting student, Casanueva lab
Harry-Jack Mann, former research assistant
Andrea Lopez-Clavijo, Head of the Lipidomics facility
Hanneke Okkenhaug, Deputy manager, Imaging facility
Greg West, former research assistant
Bebiana Da Costa Sousa, postdoc, Lipidomics facility
Anne Segonds-Pichon, Biological statistician, Bioinformatics facility
Cheryl Li, fromer postdoc, Casanueva lab
Steven Wingett, former bioinformatician
Michael Wakelam, former Institute directorOlivia Casanueva, Group leader, Epigenetics research programme
This research was funded by the European Research Council and the Biotechnology and Biological Sciences Research Council (BBSRC)
News, 6 February 2019: What can worms tell us about human ageing?
Casanueva group research pages
Animal research statement:
As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. The research described here used nematode worms called Caenorhabditis elegans (shortened to C. elegans) which is used as a model organism by researchers to understand human development and disease. The use of C. elegans in research is one of the ways by which we aim to reduce the numbers of animals we use in research.
Please follow the link to find out more about ways we work to meet the 3Rs principles: reduction, refinement and replacement in our research and when using animals in research.
About the Babraham Institute
The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through Institute Strategic Programme Grants and an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.
The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government.
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond. Funded by government, BBSRC invested £451 million in world-class bioscience in 2019-20. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
03 November 2021