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Home About Us Discovery Corner stories Research in the Gingras lab deciphers the intricacies of protein interactions

Research in the Gingras lab deciphers the intricacies of protein interactions

Dr. Anne-Claude Gingras is renowned for her studies of protein interactions that play a role in the development of cancer, drug resistance and immunity.

     
                    gingras 
 
Research in the lab of Dr. Anne-Claude Gingras is focused on understanding how a specific class of enzymes called phosphatases recognize their cellular targets. “Phosphatases control key cellular processes, and their deregulation is associated with diseases including cancer,” says Dr. Gingras. She explains that, despite their importance to human health, phosphatases have been relatively understudied. “Because proteins such as phosphatases rarely work alone in the cell, but rather associate with other proteins to exert their functions, identifying which proteins these molecules associate with is key to understanding their biological roles.”
 
For example, Dr. Gingras and her colleagues have developed an innovative computational approach—the first of its kind worldwide—designed to analyze interaction proteomics data generated by mass spectrometry. The software, called SAINT (Significance Analysis of INTeractome), will allow researchers globally to quickly assess the reliability and accuracy of protein binding data, helping to further their studies of cancer and other illnesses. Dr. Gingras has encouraged many other scientists to use SAINT, and the software is being implemented at a number of research institutions.
 
Dr. Gingras and other Lunenfeld researchers including Drs. Tony Pawson and Mike Tyers have also created the first global ‘road map’ of important protein interactions implicated in cell signaling—an achievement that will help lead to better design of experiments that will accelerate identification of new therapeutics approaches. The findings were reported in the prestigious international journal Science.
 
By using the Lunenfeld’s leading-edge mass spectrometry laboratory, the researchers studied the interactions of two key classes of enzymes known as protein kinases and phosphatases, referred to as the ‘kinome,’ in cells of the common baker’s yeast, Saccharomyces cerevisiae. Dr. Gingras and her team analyzed the entire collection of kinases and phosphatases in yeast, and uncovered a dense network of thousands of protein interactions, including many previously uncharacterized proteins. 
 
“This was the first time that a kinome had been mapped to this extent,” says Dr. Gingras. “Our findings suggest that cells are able to integrate many different signals through the global network, and this has implications for how we might design drugs to control networks in health and disease.”
 
Cells coordinate many of their activities through the actions of protein kinases and phosphatases. To date, only a fraction of these proteins in the human genome has been explored by interaction proteomics. “When these proteins malfunction, as occurs in genetic mutation or viral infection, cellular function is disturbed,” says Dr. Gingras. Blocking a protein kinase or phosphatase implicated in cancer, for example, is the basis for some anti-cancer therapies: some of the newest and most selective, or ‘intelligent,’ therapies are based on the specific inhibition of kinases that are mutated in cancer. So Dr. Gingras’ research in this area is helping lead to new and better ways to treat cancer and other illnesses.
 
 

New research at Mount Sinai Hospital

In order to conduct her research, Dr. Gingras uses state-of-the-art mass spectrometers, which are instruments that help researchers analyze and identify proteins with incredible sensitivity. As part of her research efforts, Dr. Gingras is working to develop specialized mass spectrometry tools for quantitating interaction proteomics (the study of protein-protein interactions) that will help other researchers worldwide to better analyze basic cellular processes involved in health and disease. 

 

 

 
 

 



 

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Ontario Health Study Faculty of Medicine, University of Toronto. mitacs honorary partner

 

 
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