Sunnybrook scientist use CRISPR to uncover HEB gene secret

by • September 12, 2017 • Feature Slider, Feature-Home, Featured-Slides-HomeComments Off on Sunnybrook scientist use CRISPR to uncover HEB gene secret493

Dr. Michelle Anderson (Photo by Matthew Pariselli )

Researchers at the Sunnybrook Research Institute in Toronto used the gene editing technology CRISPR- Cas9 to determine the significance of the E protein HEB. The result of their research has been described as a major discovery in the field of immunology that will have an impact on the understanding of how to treat certain diseases.

Until the team’s work, the importance of HEB in human biology was minimal. Dr. Michele Anderson, a senior scientist in biological sciences at Sunnybrook Research Institute (SRI) and associate professor in the department of immunology at the University of Toronto, collaborated with Dr. Juan Carlos Zuniga-Pflucker, chair of and professor in the department of immunology at U of T to determine the role that HEB played in the human development process. Other members of the team included Dr. Yang Li of the Peking University, and Dr. Patrick Brauer, and SRI research associate.

They found that the transcription factor HEB was critical in the early developmental process of humans. Transcription factors transcribe DNA into RNA which enabled the function of certain cell types. The team’s findings were published in the September issue of the journal Stem Cell Reports.

Anderson and her colleagues conducted a series of experiments using human embryonic stem cells which they manipulated to become T cells. T cells which play a critical role in the human immune system.

Before making the stem cells change, the team used CRISPR-Cas9 to edit out the HEB from the stem cells. This would allow them to determine what role HEB played in cellular development.

“What we found was that a lack of HEB has a profound impact on much, much earlier developmental processes in humans than we expected based on mouse studies,” Anderson said in an interview with Matthew Pariselli who wrote an article on the research for the SRI.

She said that without HEB, the formation of a type of tissue known as mesoderm during the early stages of human development encounters a “partial block.” This hindrance also affects the ability to develop other tissues that arise from mesoderm such as blood, and heart muscle cells.

Cells that managed to get through the blockage, encountered another obstruction during the stage where they are supposed to turn into hematopoietic cells. The researchers also found that without HEB, the surviving cells could not be instructed to become T cells.

To validate their findings, Anderson and her colleagues reinserted the HED genes into the stem cells. With the HEB genes back on, they found that most of the defects were corrected.

Anderson said the process provides a proof of principle for potential therapeutic applications.

The knowledge that HEB is critical to cellular development will be of great help in manufacturing T cells. This would benefit people that require immunotherapy because they have lost their T cells due to HIV, radiation, or bone marrow transplant.

Anderson has received a one-year New Opportunities grant from Medicine by Design with $50,000. She and Zuniga-Pflucker will use the money to create T cells. After that, they intend to secure more funding to move their work further along.

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