New Technologies to Solve Cellular Identity Crises
Shake a bottle of salad dressing and tiny droplets of oil suspended in water will form, caused by the chemical properties of oil and water preventing them from mixing. Inside the nuclei of our cells, similar droplets, called condensates, form from complex molecules that separate from the liquid around them in a process called phase separation. Dr. Geeta Narlikar of the University of California San Francisco has studied these condensates and the processes behind phase separation for several years, learning that condensates within nuclei are far more complex than oil droplets in water. Phase separation has been suggested to play an important role in how the genome is organized inside the nucleus, which in turn directs gene activity and controls cellular function. “If you mess up the genome packaging, the cell has an identity crisis,” says Dr. Narlikar: mutations that disrupt phase separation and cause nuclear DNA to become disorganized could lead to breakdowns in cellular processes and contribute to diseases like cancer.
As part of the 4D Nucleome program, Dr. Narlikar is collaborating with Dr. Xiaokun Shu, Dr. Bo Huang, and Dr. Vijay Ramani to develop new tools to investigate the biological relevance of phase-separated condensates inside cell nuclei. Most research on phase separation has used isolated molecules in test tubes, and new ways of manipulating and imaging condensates inside living cells are needed to understand how phase separation affects genomic function and to provide possibilities to treat diseases. For example, many cancer drugs target specific cancer-causing proteins. However, these drugs often have limitations on their use and negative side effects. Dr. Narlikar asks, “what if you could target a messed-up genome state instead of a single protein?” Therapies that target disrupted phase separation in cancerous cells could lead to more specific treatments that aren’t as likely to have side effects on healthy cells, and Dr. Narlikar’s work to create new tools to control phase separation could be the first step in developing these new treatments.
“It was not a straight path” through her career to end up in this area, says Dr. Narlikar. She began work in the field of genome packaging in her postdoctoral studies where she worked with complexes of proteins involved in DNA organization, which built off her past experiences with organic chemistry and enzymology. As part of her interdisciplinary 4D Nucleome project, she has been exposed to researchers in many different fields that have broadened her perspective about how microscopic biochemical changes can affect the entire genome. Her excitement for solving scientific puzzles has driven her through her career, even as she has experienced the “subtle challenges” of being a woman in STEM academia, with different expectations for behavior and success from students and peers. Building community with other women scientists has helped her better address these challenges. She strongly encourages women to understand the challenges of academia by talking to women faculty, but to not be deterred, as “if you’re excited about doing science and research, it’s worth it!”
Learn more about the research of Dr. Narlikar and her collaborators here.