Mucus, flatworms and us
June 21, 2012 § 2 Comments
You have something in common with a flatworm: more than 100 mucosal proteins. In a recent paper in Molecular and Cellular Proteomics, researchers showed that the freshwater planarian Schmidtea mediterranea has proteins in its mucous coating that are strikingly similar to ones in human mucus and other secretions, such as tear fluid.
The work grew out of a lab rotation project by a graduate student, Donald Bocchinfuso at the University of Toronto, who set up a collaboration between the laboratories of Michael Moran (an expert in mass spectrometry) and Bret Pearson (an expert in planarians) at the Hospital For Sick Children in Toronto, Canada. Bocchinfuso was interested in analyzing the mucous coating on the worms by MS.
“The idea to compare worms before and after removing their mucous coating started out as a simple technical step,” says Moran. “However, it grew to become a central part of the study, in part because we are at a children’s hospital and, therefore, have an awareness of the huge problem of mucousopathies, which is one way to describe cystic fibrosis.”
The mucous coating is known to be functionally essential in S. mediterranea, but it had never been molecularly characterized. The team decided to take a “proteogenomics” approach. They chopped up the proteins in the mucous coating and sequenced the peptides by MS. They matched the peptide sequences with the sequences of planarian messenger RNA. Because the planarian genome and transcriptome are not fully characterized, Moran and colleagues also looked for similarities between the planarian proteins, including the subset in mucous, and human proteins curated in databases.
The investigators found more than 100 proteins in the planarian mucus that matched ones in human secretions. Some of the matches made sense. One of them was collagen. It is hygroscopic by nature, so it serves “as an external emollient, an essential physical property of mucus-type fluids,” notes Moran. Other common proteins were ones that neutralize reactive oxygen species, which damage biological tissues. Worms naturally encounter them in the environment. Human mucus in the respiratory tract also has antioxidant properties to protect against radical damage from environmental pollutants and microorganisms.
Then there were the matches that left the investigators scratching their heads. These were histone proteins, normally associated with chromatin in the nucleus, heat shock proteins and other proteins involved in protein folding and stabilization. “We can speculate that some proteins, such as histones, may possess physical properties that allow them to moonlight in mucus in addition to their day jobs inside cells,” says Moran.
Overall, the work drives home the message that, evolutionarily, “we are more similar than different, which is why we study model organisms such as worms and flies and fish, even in a hospital research institute,” says Moran. He adds that the finding of common mucous proteins between planarians and humans could mean that planarians can be a model system to help researchers better understand the properties, functions and pathologies of human mucous proteins.
Moran says the work highlights the value of serendipity “in the absence of a rationale and hypothesis or a well-developed systematic plan.” He also notes that the work greatly benefited from the peer-review process. “Some key parts of our paper, such as the noted similarities in the proteomes of our nonparasitic Schmidtea mediterranea model and parasitic flukes, such as Schistosoma mansoni, and our use of the proteogenomics approach were really developed or expanded upon as a result of the expertise and constructive suggestions we received during the peer-review process.”