Mustafa Aydogan may be the only scientist at the Vagelos College of Physicians and Surgeons whose decision to become a researcher was profoundly influenced by the Ottoman Empire.
Mustafa Aydogan. Photo by Diane Bondareff for AP/HHMI.
Aydogan was born and raised in Turkiye, where since the Empire's heyday, circa 1500, scholars have been held in high regard. "Even today, you regularly see scientists on Turkish television educating the public," he says. "They're like rock stars."
Inspired to carry on this time-honored tradition, Aydogan wanted to begin his scientific training by studying aviation medicine in Istanbul. "But I couldn't pass the physical exams," he says.
A family friend advised him to study instead in the United States, where he landed at the University of Colorado Boulder, intent on majoring in biology or geology. Preferring a life in the laboratory over one in the field, he gravitated to the former. The same friend also told him to find a good mentor-no matter the discipline-and he found one in J. Richard McIntosh, a luminary in the field of mitosis, who set Aydogan on a path toward becoming a cell and developmental biologist.
Challenging textbook views of cellular time
During development, timing is everything, and it was during Aydogan's next stage of training that he began to challenge textbook views of cellular time. As a doctoral candidate at Oxford University, Aydogan was tasked with solving how organelles control their size and numbers. The prevailing wisdom was that the regulation of organelle abundance-like many other cellular events-must be inextricably linked to the cell's master clock, which governs the precise timing of the cell's division cycle. However, Aydogan showed that stopping the cell's master clock did not affect the cycles that drive the formation and maturation of centrioles, organelles involved in mitosis.
This finding gave birth to the concept of autonomous cellular clocks-a seemingly obscure discovery with far-reaching consequences. Follow-up studies, both from others and Aydogan's own lab, have since shown that several other subcellular events beyond centriole formation could occur through similarly autonomous cycles, indicating the broader relevance of this concept to diverse aspects of cell biology. "These clocks are normally coupled to the cell's master clock to ensure proper division," Aydogan says, "but each can also run independently to govern the timing of a specific subcellular process-especially when cells have finished dividing and require alternative means of time-keeping, or when the master clock fails."The finding gave birth to the concept of autonomous cellular clocks-a seemingly obscure discovery with far-reaching consequences.
From the beginning, Aydogan suspected that the principles underlying centriole timing had broader implications. Since then, researchers have shown that autonomous clocks control the timing of other cellular functions, with potential roles in processes ranging from quality control in embryonic development, the formation of specialized cell types, and the origins and progression of tumors.
New frontier in biological time
Autonomous cellular clocks are an emerging new frontier in biological time control, building on seminal discoveries about the cell division cycle. They are also distinct from, and not to be confused with, the circadian clock-the mother of all physiological timekeepers, which are localized in the hypothalamus and regulate body-wide functions like sleep-wake cycles and hormone secretion. Discoveries about these innate timing mechanisms were awarded Nobel Prizes in Physiology or Medicine in 2001 and 2017, respectively.
Aydogan, who joined the Columbia faculty earlier this year, isn't on the Nobel committee's radar, at least not yet, but his work is gaining traction in high places. In 2020, Aydogan was named a Sandler Fellow to establish his own small group at UCSF; the Sandler program allows exceptionally promising young scientists to establish independent research programs fresh out of graduate school. In 2023, he received a New Innovator Award from the National Institutes of Health, part of its High-Risk, High-Reward Research program, which supports young investigators with exceptionally creative and bold research ideas. In addition, Aydogan is the editor of Biological Time Control: Autonomous Clocks in Cellular Organization, Dynamics, and Function, soon to be published by Springer, the field's first textbook with contributions from investigators who have since joined the budding community of autonomous clocks.
Now settled in the Department of Genetics & Development at VP&S, Aydogan's lab is addressing three major questions in biological timing: What are the molecular mechanisms that underlie autonomous clocks? How do autonomous cycles couple to run in synchrony with each other and the cell's master clock? And what roles do autonomous clocks play in development and physiology? Answers to these questions could lead to new approaches to health promotion and disease prevention.
When his schedule allows, Aydogan likes to indulge in extracurricular matters like mathematics (see his 2020 paper on the Collatz conjecture) and discussion about the sociology of science (for example, what it means to influence others academically). "As scientists, our natural inclination is to focus on publishing and presenting our findings," he elaborates. "But some would say that mentorship is even more important for making an impact. I spend a significant amount of time with my students. It's not just teaching about science. It's also about helping young scientists refine their thinking, develop resilience, and learn how to behave as academics. I see less and less emphasis on this in academia, and it makes me sad. Though, there is no one else to blame but the system itself, burdening us with a mountain of bureaucracy. From drafting grant proposals to navigating the minutiae of lab regulations, I worry this trend will only grow worse."
In a few short months, Aydogan has found a home in New York City, whose multicultural, scholarly, and artistic landscape reminds him of Istanbul. "Starting when I was 13 or 14, I would go to the booksellers, not just to buy books. These were places for learning," he recalls. "I dedicated my doctoral thesis to these cultural institutions. I am as much as a graduate of Oxford as I am a graduate of the booksellers of Istanbul."
References
Mustafa Aydogan, PhD, is a assistant professor in the Department of Genetics and Development at Columbia University Vagelos College of Physicians and Surgeons.
