Tag: proteins

Tiny proteins found across the animal kingdom play a key role in cancer spread

Tiny proteins found across the animal kingdom play a key role in cancer spread

Researchers from McGill University have made an exciting discovery about specific proteins involved in the spread of certain cancers.

Dr. Kalle Gehring, professor of biochemistry and founding director of the McGill Centre for Structural Biology, and his team have focused on unravelling the mystery around phosphatases of regenerating liver (PRLs). These proteins are found in all kinds of animals and insects — from humans to fruit flies – and play a unique role in the growth of cancerous tumours and the spread of cancer throughout the body.

“It’s important for us to study PRLs because they are so important in cancer,” said Gehring, “In some cancers, like metastatic colorectal cancer, the proteins are overexpressed up to 300-fold.”

This overexpression of PRLs makes cancer cells more metastatic and drives the spread to other organs.

In his most recent paper, published in the Journal of Biological Chemistry, Gehring and his colleagues confirmed that PRLs exist in all kinds of single- and multi-cell animals. Data collected at the Canadian Light Source (CLS) at the University of Saskatchewan confirmed the role of PRLs in binding magnesium transporters, helping to further the understanding of how these proteins influence human disease.

Read more on the Canadian Light Source website

Attacking cancer cells from the inside out

Attacking cancer cells from the inside out

Researchers from the University of Toronto (U of T) are harnessing the power of proteins to stop cancer cells in their tracks.

“Proteins are the workhorses of the cell,” said Walid A. Houry, professor of biochemistry at U of T. “They define the cell and allow it to divide or migrate if needed.”

The team is especially interested in proteases, enzymes that chew up old or misfolded proteins and act as cellular quality control. Houry and his colleagues used the CMCF beamline at the Canadian Light Source (CLS) at the University of Saskatchewan to identify key compounds affecting these quality control mechanisms that cause cell dysfunction and, ultimately, cell death. Their research paper was recently published in Structure.

“Let’s say you have a small puppy and when you leave it in the room, it starts chewing your sofa, your carpet; it’s just hyper and eating everything up,” Houry said. The compounds cause the proteases to act like the puppy, “and the cell cannot handle this type of disruption to its machinery.”

By targeting the cell’s self-destruct button, Houry’s team, including collaborators at Madera Therapeutics, is designing a new approach to cancer therapy. Synchrotron techniques allowed the researchers to visualize the interaction between their compounds and the proteases.

Houry said hard-to-treat cancers like glioblastomas and certain types of breast cancers are good candidates for this new approach.

“Instead of inhibiting a protease, we are hyperactivating the protease, and that is unique.”

The CLS is crucial to the team’s work.

“Synchrotron technology is extremely important for us and our structure-based drug design,” he said. “We want to know why the protein is going wild when we add our compound.”

Read more on the CLS website

Image: Houry research team

MAX IV research contributes to the development of new cancer drugs

MAX IV research contributes to the development of new cancer drugs

In the battle against cancer, scientists from the drug discovery company Sprint Bioscience and researchers from MAX IV have taken important steps together toward developing new and more efficient cancer drugs with the help of fragment screening by X-ray crystallography.

Cancer accounts for nearly one out of six deaths yearly. It begins when one or more genes in a cell mutate, creating an abnormal protein or preventing a protein’s formation.

Therefore, you need to start at the protein level to fight cancer.

Sprint Bioscience is working to develop new drug candidates by identifying small molecules (fragments) that can bind targeted cancer proteins. In collaboration with researchers from the FragMAX team at MAX IV during 2019 and 2020, Sprint Bioscience optimised and developed a protein crystallisation system corresponding to a cancer protein chosen by the company.

Read more on MAX IV website

Image: Crystal incubated with fragment XB00143 mounted on the BioMAX beamline during the screening campaign.

Credit: Sprint Bioscience/BioMAX