Hodor 'holds the door' open for a potential new way to curb mosquito populations

March 18, 2020

The identification of an insect-specific metal-sensing receptor in the gut lining highlights a possible new way to curb populations of disease-transmitting insects such as mosquitoes.

In this new study led by the MRC London Institute of Medical Sciences, researchers discovered that removal of this nutrient-sensing receptor called Hodor was fatal in Anopheles mosquitoes as the insects did not make it past their larval stage.

The findings, published in the journal Nature, identify an attractive drug target that is easily accessible in the gut lining which can act to curb mosquito populations. It again emphasises the value of investigating insect specific biology, and not just human research, to lead to healthcare treatments and interventions.

The ability for cells in the gut to sense nutrients is essential to maintain homeostasis and their ability to adapt to a changing environment. Micronutrients, such as metal ions, are known to have important roles in growth and development, but our understanding of how metals are sensed is limited. These nutrient sensors are most commonly found in the gut lining, specifically in the enteroendocrine cells. However, Professor Irene Miguel-Aliaga, the principal investigator on this study, and colleagues were curious about enterocytes - which play more of a role in digestion and absorption of nutrients - and whether they have any ability to sense nutrients themselves.

They performed a genetic screen of over 100 candidate proteins thought to be involved in nutrient sensing. This screen uncovered a receptor that seems to regulate the development of larvae, particularly in nutrient-poor conditions that was expressed in the gut lining. Inhibiting the expression of this protein resulted in developmental delay, as referenced in the name 'Hodor' (an abbreviation for 'hold on, don't rush').

Hodor is a zinc-sensing protein that uses the metal to transport chloride within and out of cells, facilitating pathways that regulate nutrient-sensing and growth. Increasing the levels of zinc in the flies' diet led to increased feeding, which was reversed when Hodor was blocked. The authors suggest that the receptor helps to direct the animals to nutrient-rich food sources (metals such as zinc are produced by yeasts, which are found on fruit and other foods). Finally, they demonstrate that deleting the gene in mosquitoes is fatal, suggesting that such disease vectors could be targeted and controlled by using ingestible drugs and also could be harmless to humans due to its insect specificity.
Notes to Editors

For more information or interview requests, please contact: Sophie Arthur, LMS Science Communications Officer. Tel: +44 (0)7725 159772, Email: sophie.arthur@lms.mrc.ac.uk

Siamak Redhai, Clare Pilgrim, Pedro Gaspar, Lena van Giesen, Tatiana Lopes, Olena Riabinina, Théodore Grenier, Alexandra MIlona, Bhavna Chanana, Jacob B. Swadling, Yi-Fang Wang, Farah Dahalan, Michaela Yuan, Michaela Wilsch-Brauninger, Wei-hsiang Lin, Nathan Dennison, Paolo Capriotti, Mara K. N. Lawniczak, Richard A. Baines, Tobias Warnecke, Nikolai Windbichler, Francois Leulier, Nicholas Bellono and Irene Miguel-Aliaga. 'The intestinal zinc sensor regulates food and developmental growth' will be published online in Nature on Wednesday 18th March 16:00 UK time / 12:00 US ET, and is under strict embargo until then.

The DOI for this paper will be: https://doi.org/10.1038/s41586-020-2111-5

About the MRC London Institute of Medical Sciences (LMS)

The MRC London Institute of Medical Sciences (LMS) is a research institute which aims to advance the understanding of biology and its application to medicine. Our research is focused on some of the UK's major health challenges that arise from changes in diet (obesity, diabetes and heart disease) and increased lifespan (dementia and cancer). Through tackling fundamental questions about the links between our genes, environmental stresses such as diet, and the way our bodies age researchers aim to translate this knowledge to improve the understanding, diagnosis and treatment of diverse medical conditions. Research at the institute falls into three sections: epigenetics, genes and metabolism and quantitative biology. The LMS is core funded by the Medical Research Council (MRC), which is part of UK Research and Innovation (UKRI).

http://www.lms.mrc.ac.uk | Twitter @MRC_LMS

MRC London Institute of Medical Sciences

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.