Photo C/O Grace Gkuang

By: Saad Ahmed

A recent publication co-authored by a McMaster alumnus links a major biological pathway to fat, stress, and aging. The study was conducted by Ayush Ranawade, a PhD alumnus from the Gupta Lab at McMaster University who is currently pursuing postdoctoral studies at Harvard University, and Avijit Mallick, a University of Melbourne graduate and current PhD student in the Gupta Lab, under the supervision of Prof. Bhagwati Gupta, a professor of biology at McMaster.

The research was supported by a discovery grant from the natural sciences and engineering research council of Canada.

The team’s study demonstrated the important role of a protein called PRY-1, or Axin in mammals, which negatively regulates a well-studied Wnt signaling pathway. Wnt signaling pathways are typically associated with the regulation of cell fate determination, cell migration and organogenesis throughout embryonic development.

“Wnt proteins form a family of highly conserved, secreted signalling molecules that regulate cell-to-cell interactions during embryogenesis. Mutations in Wnt genes or Wnt pathway components lead to specific developmental defects, while various human diseases, including cancer, are caused by abnormal Wnt signaling,” reads a statement on the Gupta Lab’s website.

For decades, the specific Wnt signaling pathway has been studied for its key role in development, cell fate specification and organ formation. The pathway’s clinical importance was demonstrated by mutations that lead to various diseases, including but not limited to breast and prostate cancer, glioblastoma and type two diabetes.

According to the paper, Axins are defined as scaffolding proteins that play a significant role in signal transduction pathways through interaction with multiple factors and coordination of protein complex assembly. PRY-1, an Axin family member, showed differentially regulated genes related to lipid metabolism.

“Our paper has demonstrated, for the first time, the role of this protein in lipid metabolism. When the function of this protein is muted, the animals have a very severe lipid defect. Further study revealed that this protein might regulate lipid synthesis and involve yolk lipoproteins, which is a very interesting discovery,” said Mallick.

Research at the Gupta Lab focuses on key biological processes related to cell signalling, cell proliferation and cell differentiation. The team has been working on this study for the past three to four years, and their paper was recently accepted to the internationally reputed peer-reviewed journal PLOS ONE, which is published by the “Public Library of Science” of the United States of America.

“Initially, our focus was to understand the processes that this protein regulates and as such a whole genome transcriptome profiling was done in the mutants. For the involvement of this pathway in cancer and organ development, we were expecting genes mostly involved in those processes,” said Mallick. “To our surprise, we found highly enriched genes involved in lipid metabolism and the aging process.”

After a number of years involving rigorous study, the team presented their findings on the crucial protein.

“One part of our research got published recently in PLOS One where as the research on aging is still going on, which will hopefully be submitted next year for publication,” said Mallick.

The open access and peer reviewed study is available on the PLOS One website. More information about the Gupta Lab can be found at  

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