Single-cell fluorescence microscopy sheds light on stress-regulated gene mechanisms

When it comes to developing advanced technology to further scientific research, Maria Vera Ugalde, PhD, an Assistant Professor in the Department of Biochemistry at McGill University’s School of Biomedical Sciences, proves that necessity is the mother of invention.

After obtaining her PhD in cell biology from the University of Navarra, Spain, Prof. Vera Ugalde went to NYU Medical Center for postdoctoral training, then joined Robert Singer’s lab at Albert Einstein College of Medicine. “The cell and molecular biology techniques I was using were not powerful enough to answer all my biological questions so I dedicated five years of my post-doc to develop and use single-molecule imaging techniques in order to better understand and study gene expression regulation,” she says. “I started in biomedical research looking for gene therapy for cancers and evolved into a molecular biologist looking at individual mRNA molecules.”

In Prof. Vera Ugalde’s lab at McGill, her team is studying how eukaryotic cells survive stress conditions (environmental changes that damage proteins) that threaten cell functionality. Using single-molecule fluorescence microscopy combined with biochemical and genetic methods, their research aims to decipher how cells produce the components of the stress response known as the heat shock proteins (HSPs). The success of the stress response relies on the finely-tuned regulation of the HSP mRNA lifecycle. However, the unbalanced expression of HSPs leads to a variety of diseases that ranges from cancer to neurodegeneration.

“This technology allows us to see one molecule of RNA inside the cell,” says Prof. Vera Ugalde, “and these techniques are unique in the amount of information they provide to study the regulation of gene expression.”

A promising future for treating disease

Prof. Vera Ugalde’s lab uses primary neurons as a model for their research. “We have discovered that the neurons are able to regulate the localization of the mRNAs that encode for the HSPs to different neuronal compartments,” she says.

Prof. Vera Ugalde says that, though it will take some time, her lab’s goal is to discover ways to treat age-related diseases. “Our hope is that one day, we will be able to control the localization of the mRNAs that encode for these HSPs and direct them to the areas of the neuron which have the highest accumulation of misfolded or non-functional proteins to help the neuron recover the protein homeostasis.”

The issue of global warming also plays a role in the discussion of environmental changes that damage proteins. “We are more and more exposed to heat waves which also activate the heat shock response,” Prof. Vera Ugalde explains. Using simple organisms like yeast, her lab is trying to better understand how organisms regulate this heat shock response and seeing if they can manipulate the response to make organisms more resistant to heat stress.

A very strong community

Prof. Vera Ugalde is looking forward to the collaboration that will come with the new McGill Centre for RNA Sciences. Having already been approached by several investigators at McGill to use her lab’s technology and the computational guidelines they’ve developed to analyze data, Prof. Vera Ugalde would like to make it available to everybody. She hopes the input from more researchers will also help her lab make the technology even better.  

She also sees the opportunities to work with other RNA scientists, share resources and engage in meaningful discussions. “It’s always very stimulating talking with people in the same community, with so many different fields of research and interests, but having that common point to start a conversation,” she says. “The RNA people at McGill, and generally in Montreal, make up a very strong community with very good scientists, so to put all of us together is wonderful, and a great development for the city.” 


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