Sophie Dumont, PhD, was on track to become a physicist when she stumbled upon a mind-blowing description of cell division at a Berkeley auto shop while waiting for her clunker to be fixed.
“My old car was being worked on so I picked up a book left by a previous customer titled “Landmark Papers in Cell Biology” and started reading about machines inside our cells that divide chromosomes,” recalled Dumont, a UC Berkeley grad student at the time. “I thought, ‘Whoa, I want to work on this.’”
After watching a cell divide, Dumont, now an associate professor in UCSF’s Department of Bioengineering and Therapeutic Sciences, says she was hooked. “It looked so beautiful, a perfectly orchestrated process – just like a symphony. How do cells do that?”
Today, Dumont, winner of the 2021 Byers Award for Basic Science, focuses on finding out how, as well whether therapeutic targets exist to ensure equal – and healthy – division of chromosomes. As she notes, even after more than 100 years of study, much is still unknown about cell division, a process that occurs in each body a trillion times a day.
“Cells have one supremely important role: to equally divide their chromosomes. If they fail in that process, birth defects or cancer can result,” says Dumont. “While we know the parts required for cells to accurately divide chromosomes, we don’t understand how they work together to prevent mistakes – and how they fail.”
Support for Basic Science Research
As the Byers Award winner, Dumont delivered the 2021 lecture titled “An Orchestra Without a Conductor: A Symphony of Dividing Chromosomes” on April 27. Established with a philanthropic gift from Brook and Shawn Byers and their sons Blake and Chad, the Byers Award is given annually to recognize outstanding research by a mid-career faculty member. A long-time member of the UCSF Foundation Board of Directors, Brook Byers called scientists his personal heroes and said this year the Byers family will increase the award to $250,000 in hopes of accelerating the scientific process.
“Scientists perform the closest thing I have seen to magic as they uncover the mysteries of biology and chemistry and physics,” he told the lecture audience. “I applaud the doctors, nurses and staff who deliver those translated breakthroughs to patients. UCSF is truly a home of heroes – many of whom are in the audience today. My family and I salute you all.”
UCSF Chancellor Sam Hawgood, MBBS, the Arthur and Toni Rembe Rock Distinguished Professor, described basic science as the “beating heart” of UCSF and Brook Byers as a rare philanthropist who understands that medical “miracles” often begin with discoveries made by basic scientists.
Hawgood paid tribute to the discoveries arising from this type of research, calling them critical for unlocking cures of disease across the broad spectrum, including cancer, neurodegeneration, diabetes, heart disease, and global maladies. He noted that during the pandemic, UCSF’s Program for Breakthrough Biomedical Research (PBBR) issued a call for COVID-19 research and UCSF’s basic scientists responded.
Researchers offered proposals for better understanding the coronavirus, detecting infection with new technologies, and delivering therapeutics to address the public health crisis. PBBR, which supports high-risk ideas unlikely to attract funding from the National Institutes of Health (NIH), funded research that resulted in papers published in scientific journals including Proceedings of the National Academy of Sciences, Nature Communications and Science.
“The impact of PBBR has never been more robust,” Chancellor Hawgood said. “As of this year, the program has generated almost 3,400 peer reviewed scientific publications – that’s almost three new papers every week – over 100 patents, and 335 follow-through NIH grants. Founded by the late Herb and Marion Sandler, PBBR stands among the crown jewels of our basic science work.”
Studying the ‘Machines’ Inside Cells
During her lecture, Dumont demonstrated that she is clearly a basic scientist who has drawn on her training at several of the world’s great universities: Princeton, Oxford, UC Berkeley and Harvard. Though switching careers meant a deep dive into biology, Dumont relied on her education as a physicist to understand cell division by understanding the physical principles driving the process. She told the virtual audience of more than 200 that she has spent the last many years studying the “machines” that push and pull inside each cell to divide their contents again and again and again until they form a human body.
“When I moved to biology, I remember feeling completely lost for the first few years,” said Dumont, who is also an investigator with the Chan Zuckerberg Biohub. “When I became more confident, I understood that I can ask a different set of questions and bring a different set of tools to do something that is different and new. And that is good.”
The Dumont Lab focuses on the spindle, a “machine” operating in the middle of the cell to segregate chromosomes and ensures each new cell receives a full set of the genome to perform its function in our bodies whether it’s replication or repair. If the spindle performs its task poorly and gives a new cell the wrong number of chromosomes, the result often is disease. Dumont and her team want to know: How does the spindle build itself? How does it know how to divide its chromosomes equally? And conversely, how do mistakes occur?
“I have hands and eyes so when I divide a single Popsicle for my twin daughters, it is quite easy to divide it fairly,” Dumont says. “But cells don’t have hands or eyes. How do they know how to equally segregate their contents? There must be a machine that is highly regulated that makes these chromosomes divide. It doesn’t just happen randomly. Who is the conductor driving all this?”
Cancer has become a recent focus in her lab. Again, she says, not a lot is known, but she and her team are pursuing promising leads. “We hypothesize that spindles in cancer cells may be mechanically stronger to allow them to divide in an environment that is more crowded. We can dream that this is a therapeutic window to target the unique vulnerabilities or superpowers of cancer cells that are not there in normal healthy cells. The big dream is to target mechanical vulnerabilities just like we currently do for many unique biochemical vulnerabilities.”
As a young girl growing up in a small town in Québec, Canada, Dumont heard her father, Claude Dumont, MD, who had experienced UCSF as a medical school graduate, describe the university as a playground for adults where your mind could roam free. Claude Dumont did not live to see his daughter join the faculty at UCSF, but his words left their mark.
Upon arriving here in 2012, she said, “Because of all I had heard about this place growing up, UCSF felt like home.”