To celebrate the International Day of Women and Girls in Science, we are highlighting the work of a successful early-career researcher at the Life Sciences Institute
As a postdoctoral researcher, Dr. Sheila Teves used cutting-edge technology to make a discovery about stem cell division that overturned a misunderstanding that had persisted for 20 years.
We sat down with Dr. Teves in early February, 2020 to ask her about this paradigm-shifting finding, published with her colleagues at UC Berkeley in eLife in 2016 (https://elifesciences.org/articles/22280) and the research she plans to pursue here at UBC.
Dr. Teves studies transcriptional regulation in mouse embryonic stem cells (ESCs). ESCs turn on a pattern of genes that allow them to maintain their “stem” properties and self-maintain indefinitely, while also retaining a counter-ability to change this profile and turn on a different pattern of genes that allow them to become any other cell type in the body. How cells control this pattern of gene expression is the focus of Dr. Teves’ research.
“We’re trying to work out how stem cells make sure they stay as stem cells after each cell division: we’re focusing on the early events after cell division,” says Dr Teves.
“It all started a few years ago when I was still a post doc. I was already interested in the idea of cell memory – mitotic memory,” adds Dr. Teves. “Whenever the cells divide, there is a massive rearrangement of the genome, the cells condense the mitotic chromosomes, a lot of normal functions are shut off. How do the new daughter cells restart the same transcriptional program as the original mother cells?”
What is transcription, and why is it important to capture it in live cells?
In the human body, there are more than 200 different cell types, all coming from a single zygote. Almost every single cell in our body retains the same genetic input. The only difference is how each cell uses the genetic input, or transcriptional regulation. The specific genes required for a cell type to function must be turned on, while other genes that may specify other cell types are kept silent. This is why transcriptional regulation is a very important component of cell identity.
At the time of Dr. Teves’ postdoctoral training, it was thought that transcription factors – proteins that can bind to DNA to turn adjacent genes on and off – were detached during cell division. Using cutting-edge single molecule live-cell imaging in combination with gene editing and genomics approaches, Dr. Teves was able to show transcription factors hover over chromosomes during division. In vivo, many transcription factors are able to bind to, and interact with DNA during cell division – an efficient way for newly formed cells to reset the pattern of gene activity for their cell type.
“When I started looking at things as they happen in the cells and compared to biochemical methods…I always got conflicting results,” she says. “It took a while to finally meld the two results….all of the other (biochemical) techniques required fixing the cells. Essentially, 20 years of literature was wrong because they all relied on that first step of fixing the cells.”
“It made me realize the importance of in vivo work under live, native conditions with as little interference as possible. It’s not that the literature was deliberately wrong, it was the limitation of the technology.”
Moving forward: uniting groundbreaking insights with unique capacities at the LSI
“In the near future, we’re trying to establish a few interdisciplinary technologies in our lab”, says Dr. Teves, who joined the Department of Biochemistry and Molecular Biology and the LSI as an assistant professor in Summer of 2018. “We’ve now established a lot of genomics analyses, but we’re also trying to establish our single molecule live cell imaging. Together they paint a comprehensive view of what’s going on in the cell.”
It was this technology that allowed Dr. Teves to make her groundbreaking observations about the nature of transcriptional regulation during stem cell division.
She is now trying to set up a microscope to watch even the fastest events that happen in living cells, collaborating with scientists in the LSI Imaging facility who have the capacity to build their own microscopes which can be used for special applications such as hers.
With these tools, Dr Teves is interested in exploring the real challenges arising in regenerative medicine. “How do stem cells become what you want in the most efficient and effective way,” she asks. “That’s the long-term objective of my research. My particular focus is studying mechanisms for how these cells maintain their transcriptional program over time. Or change their transcriptional program.”
Championing Open Access and pre-print publication as a way to make science widely accessible
Dr. Teves is also a strong advocate for open access publications. As a postdoc, she was the first in the lab to push for uploading publishable results to pre-print servers, such as bioRxiv, an open access repository where readers can read and comment on papers before they’re even published. “You have to be careful about it,” she warns, “make sure the readers are aware that the research is still unpublished!” She also chooses to publish mostly, if not entirely, in open access journals.
“Ultimately, it boils down to who’s funding the research. Taxpayers funding the research shouldn’t have to pay money to access the research that they paid for. I believe education is important. If this information could help people, there shouldn’t be any road blocks to that.” She is also a fan of Twitter, as an alternative means of getting the information out to the general public.
Advice for science-interested girls, and female trainees: don’t be afraid to fail
Dr. Teves got her start in research through a program at the University of Wisconsin called Research Experience for Undergraduates. A recommendation from there led to a research position at the NIH, where a mentor encouraged her to pursue graduate training instead of medical school. She did her PhD at the University of Washington, followed by a post-doctoral fellowship at University of California, Berkeley.
Asked what her advice would be for young women interested in research, she said, “People idealize heroes in science, but 90% of what we do here comes about after many failures.
“Don’t be afraid to fail. That’s the first thing. What got me here was getting back up and not giving up after many failures, for example, rejections for schools, fellowships, lab positions, papers. There’s so much [information] that might tell you that you don’t belong somewhere, but you do. If you want to belong there, you belong there, and you can make it happen if you don’t give up.”