Science Talk

Having a bad air day? Cilia to the rescue

A multiciliated cell from the human airway.
A multiciliated cell from the human airway. PHOTO: DR SUDIPTO ROY

These hair-like projections help clear mucus that traps pollutants entering our airways

Singapore suffered the return of the haze just a few months back, with PSI readings breaching unhealthy levels on several occasions.

Have you ever wondered why most of us are still able to breathe normally despite the bad air quality? It is all thanks to a special kind of cell within our airways which works extra hard during these times to keep the pollutants we breathe in from harming us.

These cells are called multiciliated cells and, on their surface, they bear a brush-like specialisation of hundreds of cilia. The cilia are slender hair-like projections that beat continuously in a rhythmic manner to clear the mucus that traps pathogens and pollutants entering our airways with every breath we take.

Multiciliated cells can be damaged in patients with defects in genes that are required to make cilia. Those suffering from asthma and chronic obstructive pulmonary disorder also have problems with their multiciliated cells. People with these disorders have a particularly difficult time coping with unhealthy air.

At Singapore's Institute of Molecular and Cell Biology, we have discovered a protein called Gmnc, which we have named a "master regulator" for multiciliated cell formation. Our research focused on two model organisms - the zebrafish embryo and the tadpole.

These two species are known to be readily amenable to genetic analysis. It may seem perverse that we chose to investigate multiciliated cell formation in these animals that do not breathe air like us, but multiciliated cells are highly conserved in evolution. This means that they behave similarly across a wide variety of animal species.

  • About the writer

  • Dr Sudipto Roy, 45, is a senior principal investigator at the Institute of Molecular and Cell Biology at the Agency for Science, Technology and Research (A*Star). He also holds adjunct appointments with the biological sciences and paediatrics departments of the National University of Singapore.

    He is trained as a developmental biologist. His lab examines how genes regulate cell and tissue formation and how genetic dysfunction affects the pathology of human diseases.

    He is also keenly interested in music, art and wildlife. He plays the cello, paints and has a collection of butterflies from around Asia. He started writing to communicate scientific discoveries to the general public, and won a merit award at last year's inaugural Asian Scientist Writing Prize competition.

Multiciliated cells similar to those in our airways decorate the nasal cavity and kidney tubes of zebrafish embryos. In the nose, the cilia beat to drive in water laden with attractive or repulsive substances that the fish can smell, whereas in the kidney, the cilia promote urine flow. The skin of the tadpole also has multiciliated cells, and here they function much like their counterparts in our airways - to clear a protective layer of mucus that traps pathogens and toxins in the water.

When we inactivated the production of Gmnc in the zebrafish embryo and the tadpole, multiciliated cells failed to form or were significantly reduced in number. On the other hand, rather strikingly, when we engineered tadpoles to make more of the Gmnc protein, they responded by generating several-fold more multiciliated cells.

So what's next for Gmnc? Well, there is strong evidence that the relevance of our findings extends to mammals. A similar study in Europe has shown that in mice, Gmnc is both necessary as well as sufficient for multiciliated cell development, suggesting that the protein also functions in multiciliated cell formation in humans.

Our work, together with the mouse study, strongly implicates Gmnc in transcriptional regulation - switching on the expression of genes.

As a master regulator, Gmnc is much like the conductor of a symphony orchestra. We surmise that it directs the expression of a whole retinue of genes that together function in multiciliated cell formation.

The most exciting avenue that we wish to explore is the relevance of Gmnc in human respiratory disorders. The prospect of Gmnc dysfunction in inherited respiratory diseases is high, and due to its master regulatory property, the protein may also hold the key to a therapeutic tool to allow multiciliated cells to regenerate.

Genetic screening for Gmnc mutations in patients with respiratory disorders is already in the works. Whether Gmnc can facilitate the regeneration of the ciliated cells after injury to the airways will require new projects that will take at least five years to reach a conclusion.

The next time you take in a breath of air, be grateful to these multiciliated cells - the janitors of our airways.

The tireless beating of their cilia slowly but surely gets rid of germ- and toxin-loaded mucus, and keeps us out of harm's way.

A version of this article appeared in the print edition of The Straits Times on February 05, 2016, with the headline 'Having a bad air day? Cilia to the rescue'. Print Edition | Subscribe