Every day, your body replaces billions of cells—and yet, your tissues stay perfectly organized. How is that possible?
A team of researchers at ChristianaCare's Helen F. Graham Cancer Center & Research Institute and the University of Delaware believe they've found an answer. In a new study published today in the scientific journal Biology of the Cell, they show that just five basic rules may explain how the body maintains the complex structure of tissues like those in the colon, for example, even as its cells are constantly dying and being replaced.
This research is the product of more than 15 years of collaboration between mathematicians and cancer biologists to unlock the rules that govern tissue structure and cellular behavior.
"This may be the biological version of a blueprint," said Bruce Boman , M.D., Ph.D., senior research scientist at ChristianaCare's Cawley Center for Translational Cancer Research and faculty member in the departments of Biological Sciences and Mathematical Sciences at the University of Delaware. "Just like we have a genetic code that explains how our genes work, we may also have a 'tissue code' that explains how our bodies stay so precisely organized over time."
Math Meets Medicine
The researchers used mathematical modeling—essentially, creating a computer simulation of how cells behave—to see if a small number of rules could account for the highly organized structure of the lining of the colon. That's an ideal place to study: cells in the colon renew every few days, but the overall shape and structure stays remarkably stable.
After running many simulations and refining their models, the team identified five core biological rules that appear to govern the structure and behavior of cells:
- Timing of cell division.
- The order in which cells divide.
- The direction cells divide and move.
- How many times cells divide.
- How long a cell lives before it dies.
"These rules work together like choreography," said Gilberto Schleiniger, Ph.D., professor in the University of Delaware's Department of Mathematical Sciences. "They control where cells go, when they divide and how long they stick around—and that's what keeps tissues looking and working the way they should."
Decoding Human Tissue
The researchers believe these rules may apply not just to the colon, but to many different tissues throughout the body—skin, liver, brain and beyond. If true, this "tissue code" could help scientists better understand how tissues heal after injury, how birth defects happen and how diseases like cancer develop when that code gets disrupted.
Boman explained it this way: "Your tissues don't just grow and shrink randomly. They know what they're supposed to look like, and they know how to get back to that state, even after damage. That level of precision needs a set of instructions. What we've found is a strong candidate for those instructions."
This work also has important implications for the Human Cell Atlas , a global scientific collaboration working to map every cell type in the human body. While the Atlas aims to catalog what each cell is and what it's doing at a given moment, this new research offers a dynamic framework for understanding how those cells stay organized over time. By identifying simple, universal rules that govern cell behavior and tissue structure, the findings could help guide future efforts to not only describe cells, but predict how they behave in health and disease.
Implications for Disease and Discovery
One reason the team turned to mathematical models, rather than traditional biology experiments, is that it's extremely difficult to observe how every single cell in a tissue behaves in real time. But with computer models, researchers can run simulations that reveal patterns and dynamics hidden from view.
This kind of collaboration between biology and math reflects a broader shift in how scientists approach complex problems. It also aligns with national priorities: the National Science Foundation's " Rules of Life " initiative challenges researchers to uncover the fundamental principles that govern living systems. This study is a strong step in that direction.
Next steps for the team include testing the model's predictions experimentally, refining it with additional data and exploring its relevance to cancer biology—especially how disruptions to the tissue code may lead to tumor growth or metastasis.
"This is just the beginning," said Schleiniger. "Once you can identify the rules, you can begin to ask entirely new questions, and maybe even learn how to fix what's gone wrong."
Funding for this project was provided by the National Institutes of Health, the National Science Foundation, The Lisa Dean Moseley Foundation, the Delaware Bioscience Center for Advanced Technology (CAT) and the UNIDEL Graduate Research Fellowship.
About ChristianaCare
Headquartered in Wilmington, Delaware, ChristianaCare is one of the country's most dynamic health care organizations, centered on improving health outcomes, and innovating to make high-quality care more accessible, equitable and affordable. ChristianaCare includes an extensive network of primary care and outpatient services, home health care, urgent care centers, three hospitals (1,430 beds), a freestanding emergency department, a Level I trauma center and a Level III neonatal intensive care unit, a comprehensive stroke center and regional centers of excellence in heart and vascular care, cancer care and women's health. It also includes the pioneering Gene Editing Institute.
ChristianaCare is nationally recognized as a great place to work, rated by Forbes as one of the nation's best employers for diversity and inclusion. ChristianaCare is rated by Newsweek as one of the World's Best Hospitals and is continually ranked among the best in the U.S. in national quality and safety ratings. ChristianaCare is a nonprofit teaching health system with more than 260 residents and fellows. With its groundbreaking Center for Virtual Health and a focus on population health and value-based care, ChristianaCare is shaping the future of health care.
About the Cawley Center for Translational Cancer Research
The Cawley Center for Translational Cancer Research (CTCR) at the Helen F. Graham Cancer Center & Research Institute moves research from the laboratory bench to the patient's bedside by applying basic science toward potential therapies. The Cawley CTCR is where scientists study the molecular causes of cancer and tissue engineering, all targeted to better treatment for patients. Groundbreaking findings and current studies at the center are helping to prevent, better detect and stop the growth of many cancers — and as a result reducing cancer incidence and mortality rates in Delaware and beyond.
About the University of Delaware
The University of Delaware traces its roots to 1743, making it the seventh-oldest higher education institution in the country. UD's tradition of excellence continues today in both the classroom and the laboratory, with consistent ranking among the top 40 public universities. Beyond its Georgian-inspired main campus in Newark, Delaware, UD has locations in Wilmington, Dover, Georgetown and Lewes, in addition to a growing online learning environment.
UD is a state-assisted, privately governed institution and one of a select group to hold the triple Land Grant, Sea Grant and Space Grant designation. UD is classified nationally as a Research 1 (R1) university for its very high research activity and doctorate production, a designation held by less than 5% of U.S. colleges and universities. UD also is recognized as a Community Engaged University for its long tradition of applying knowledge and creativity to the critical challenges facing communities in Delaware and around the world.
About the University of Delaware's Department of Mathematical Sciences
The University of Delaware's Department of Mathematical Sciences offers a diverse suite of programs – from actuarial science and applied mathematics to mathematics‑and‑economics, mathematics education, and quantitative biology – designed to develop both deep theoretical insight and practical problem-solving skills. The department's vibrant community of scholars and educators is anchored by the Mathematical Sciences Learning Lab and the Center for Applications of Mathematics in Medicine. Faculty and students collaborate on cutting‑edge research across pure and applied mathematics – exploring topics such as algebra, topology, probability, and graph theory – and join forces with colleagues in computer science, data science, engineering, biology, and neuroscience.
About the Department of Biological Sciences at the University of Delaware
The Department of Biological Sciences at the University of Delaware is a dynamic and interdisciplinary community of scholars, researchers, and educators. With a proud legacy of academic excellence and a strong track record of external research funding, the department offers an exceptional undergraduate experience that blends classroom instruction, problem-based learning, hands-on lab training, and mentored research in faculty labs. This comprehensive approach equips students with the skills and knowledge to thrive in a wide range of careers or advanced studies. At the graduate level, the department focuses on uncovering the molecular mechanisms of life, using bacterial, invertebrate, and vertebrate model systems to advance understanding and improve human health and society. Our collaborative teaching and research environment spans molecular biology and genetics, developmental biology, cell and tissue physiology, microbiology, and science education – creating a vibrant, inclusive, and impactful scientific community.
