'MaMTH' advance: New technology sheds light on protein interactions

Mar 24, 2014

Scientists have a better way to study human proteins—large molecules that are part of every cell in the body—thanks to a new technology developed by University of Toronto researchers. The technology tracks a class of proteins called membrane proteins as they interact with other proteins to either maintain health or contribute to disease.

Membrane proteins make up about one third of all proteins in the human body, and their malfunction is associated with more than 500 diseases. But they've been hard to study because understanding their role depends on observing their interactions with other proteins.

"This technology gives us a new tool to examine in their natural environment of the human cell," said Igor Stagljar, a Professor in the Donnelly Centre for Cellular and Biomolecular Research. "As well, it's sensitive enough to detect minor changes upon introduction of drugs, so it should prove useful in the development of therapeutics, particularly for cancer and neurological diseases."

The journal Nature Methods published the research online today.

Stagljar and his colleagues also applied the , which they dubbed MaMTH (for Mammalian-Membrane Two-Hybrid assay), to identify a protein that plays a role in the most common form of called non-small cell lung cancer.

That protein, CRKII, interacts with another protein called an epidermal growth factor receptor. Mutation of this receptor—which is already the target of several cancer drugs either approved or in development—causes a proliferation of .

"CRKII most likely regulates the stability of mutated epidermal growth factor receptors and drives cancer growth by promoting signaling, or communication, within cancer cells," said Julia Petschnigg, lead author on the paper and a postdoctoral fellow at U of T. "We found that a combinatorial chemotherapy that inhibits those mutated receptors and CRKII could be beneficial in treating lung cancer."

The research was highly collaborative, involving clinicians, bioinformaticians and researchers in five labs around Toronto and Boston. Stagljar and his lab spent four years developing the MaMTH technology, which they adapted from a similar technology that captures protein-protein interactions in yeast.

Next, the group will apply their technology to study some of the 500 proteins that are mutated in other human diseases.

"You simply cannot publish meaningful research in proteomics without collaborating," said Stagljar, who is also a Professor in the Departments of Biochemistry and Molecular Genetics. "Fortunately, we have access to great cross-disciplinary expertise and infrastructure in the Donnelly Centre. Science is alive and well in Toronto."

Explore further: Microbial diversity throughout ice sheet melt season

More information: The Mammalian-Membrane-Two-Hybrid (MaMTH) assay for probing membrane protein interactions in human cells, DOI: 10.1038/nmeth.2895

Related Stories

Protein inhibits cancer cell growth

Dec 21, 2009

(PhysOrg.com) -- Researchers at the University of Toronto and Goethe University in Germany have discovered a protein that can inhibit the growth of cancer cells, providing crucial clues for the future development of new drugs ...

New knowledge on molecular mechanisms behind breast cancer

Sep 25, 2013

Researchers at University of Copenhagen have gained more insight into the molecular mechanisms of importance for, for example, cancer cell growth and metastasis. The research objective is improved and more targeted drugs. ...

Recommended for you

The vital question: Why is life the way it is?

8 hours ago

The Vital Question: Why is life the way it is? is a new book by Nick Lane that is due out on April 23rd. His question is not one for a static answer but rather one for a series of ever sharper explanations—explanations that a ...

Food poisoning: New detection method for bacterial toxin

9 hours ago

The Bacillus cereus bacteria is one of the potential causes of food poisoning. Indeed, a recent study in Analytical and Bioanalytical Chemistry shows that this versatile pathogen produces 19 different varian ...

Detailing heterochromatin formation at the onset of life

10 hours ago

Antoine Peters and his group at the Friedrich Miescher Institute for Biomedical Research (FMI) have elucidated the mechanisms controlling the packaging of chromatin in the early embryo. They have identified ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.