Carolina researcher develops a way to see organelles in action
Sarah Cohen and two others will pioneer a method to view these molecular structures and their interactions in live stem cells.
Cells constantly shuttle around the body to complete different tasks, from wound healing to metastasis. Within each cell exists a bustling, dynamic metropolis of organelles, small molecular structures with specific functions. Recent research suggests that small changes in organelles can play big roles in human health and disease. For example, many mutations that cause neurodegenerative diseases are in proteins that help organelles connect and interact.
But so far, it’s been hard for scientists to see organelle interactions in action and determine their roles in cell differentiation and function. Electron microscopy requires cells to be dead, fixed and sectioned, which prevents the ability to draw conclusions on complex organelle behavior in live cells and fully capture 3D organelle structure. Similarly, fluorescence microscopy uses lasers that can damage cells, preventing the long-term visualization of changes in organelle interactions.
Now Sarah Cohen, an assistant professor in the UNC School of Medicine’s cell biology and physiology department, and two collaborators (Assaf Zaritsky from Ben-Gurion University in Israel and Shalin Mehta from the Chan Zuckerburg Biohub in San Francisco) are pioneering a new way to look at organelle interactions during cell fate specification. Their method combines label-free imaging, fluorescence microscopy, and machine learning to visualize and analyze eight organelles at a time in live stem cells. The trio recently received a 2024 Allen Distinguished Investigator Award, a $1.5 million award that funds the development of paradigm-shifting tools for the research community.
“I’m very excited about this award because it’s a collaboration with two of my colleagues. It’s an interdisciplinary project with the high-level goal of understanding how cells reorganize during development to support different physiologies,” said Cohen.
The results they’ve seen so far suggest that changes in organelle contacts could play key roles in supporting cell differentiation and function. “We’re proposing to follow up on these observations but then also extend them to different cell types, including heart muscle cells and liver cells,” said Cohen.
Once the team has identified what organelle contacts are important for a specific cell type, they plan to disrupt those contacts to see if they can prevent differentiation. Conversely, they will also try to drive changes in cell function and differentiation by forcing different organelles to make contact.
“A year ago, I would have said that driving a single organelle contact would not be enough to affect cell physiology, but we’re starting to see indications of that,” said Cohen.
Whether changes in organelle contacts can cause meaningful consequences to human health remains unclear. For now, the first step in answering this question is developing better tools for organelle visualization in live cells.
“I’m really excited to establish these collaborations and develop new methods for studying organelle communication that I hope will be useful for other groups beyond ours,” said Cohen. “And I’m excited to test this crazy idea of whether driving organelle contacts can change cell function.”
