AYS Webinar Summary - Session 5: Unifying Principles of Hierarchical Organization: Assembly, Function, and Dysregulation in Biology
Session Summary
The Biggest Question for My Science event series fosters a deeper understanding of the fundamental questions that drive scientific discovery. Each session features an AYS Fellow and one to two prominent scientists from related fields discussing the most critical question in their research and the scientific community's approach to it.
Session 5 held on August 13, 2025 (CST), titled "Unifying Principles of Hierarchical Organization, Assembly, Function, and Regulation in Biology". Professor Yi Lin highlighted multivalent interactions and their role in phase separation, circadian rhythms, and cell cycle progression. Professor Tian Xue then expanded the discussion beyond the cellular level, focusing on neural circuits and behavior, particularly the light sensation system from an evolutionary perspective. Professor Xiaofan Wang shifted the focus to cancer research, exploring how genetic and epigenetic changes in cells lead to the evolution of cancer.
This webinar emphasized the importance of understanding hierarchical organization across biological scales and its potential for novel therapeutic approaches. The session concluded with a Q&A and discussion, encouraging audience participation on key questions related to unifying logic, structure-function interplay, and therapeutic applications of organizational principles.
Summary of Speakers’ Presentations
Professor Yi Lin: Dynamic Assembly of Biomolecules Into Cellular Architectures
Professor Yi Lin discussed the dynamic assembly of biomolecules into cellular architectures, particularly within the nervous system. She emphasized that the organization of biomolecules into higher-order cellular structures may represent a new principle. Professor Lin highlighted the role of multivalent interactions in driving phase separation, which orchestrates the formation of cellular compartments. Her research on circadian rhythms showed how dynamic protein condensates regulate protein translation and influence circadian behavior in mice. She also noted that disruption of phase separation is implicated in diseases like neurodegeneration and proposed further exploration into mechanisms of proteins with intrinsic disordered regions, atomic resolution cellular maps, and potential of targeting biomolecular structures for novel therapies.
Professor Tian Xue: Eyespot, Retina to Visual Circuits: Evo-devo Perspective of Hierarchical Cell-organ-system Organization of Light Sensation of Life
Professor Tian Xue explored the evolution of light-sensing systems, from simple eye spots in single-celled organisms to complex retinas in higher animals. He explained the shift from two-layered to three-layered retinas and the development of specialized structures, like the macula and fovea. Professor Xue also discussed how light affects not only vision but also non-imaging functions, such as regulating circadian rhythms and metabolism. His talk highlighted the evolutionary complexity of sensory systems and neural connectivity, underscoring their importance for organismal fitness and survival.
Professor Xiaofan Wang: Tumorigenesis: a Chaotic Process Reversing The Hierarchical Organization Of Life Under Evolutionary Pressure At The Molecular And Cellular Level
Professor Xiaofan Wang discussed cancer as a complex and evolving disease driven by both genetic and epigenetic changes. He emphasized the role of cancer cells bypassing developmental control to proliferate uncontrollably. His talk covered the history of cancer research, focusing on the discovery of oncogenes and the core hallmarks of cancer cells, such as evasion of cell death and tissue invasion. Professor Wang highlighted the genomic instability of cancer and its resistance to treatments, as well as the tumor microenvironment's role in immune evasion. He concluded with ongoing research efforts to identify new therapeutic mechanisms.
"The Biggest Questions" Raised and Discussed by Speakers
In this session, the speakers engaged in an in-depth exploration of the following questions, weaving their insights closely with the audience’s real-time queries and reflections. The resulting discussions were both intellectually stimulating and highly relevant. We have therefore compiled a concise yet comprehensive summary of each significant question raised, accompanied by the professors’ heartfelt aspirations that these dialogues will inspire and encourage more young researchers to actively contribute to advancing this field of study.
Q1: Is there a unifying logic behind hierarchical organization (e.g., molecules → cells → circuits) in biology?
Professor Yi Lin sees the unifying principle in hierarchical organization through the lens of molecular and cellular dynamics. She believes that understanding how the interaction among different molecular components within cells is crucial. Advances in high-resolution imaging and omics technologies, alongside computational methods like AI and mathematics, are essential for mapping these relationships. She emphasizes that although new technologies are rapidly evolving, classic tools such as biochemistry and genetics remain foundational to studying the organization of molecules and cells. Ultimately, she suggests that combining these approaches will lead to a better understanding of the cell as an organized structure.
Professor Tian Xue acknowledges the complexity of identifying a unifying principle in biology, stating that evolution plays a significant role in shaping biological systems. He suggests that nature improvises through evolutionary processes, often arriving at "local maxima" in fitness, rather than perfect solutions. For example, in the context of the human eye, he explains that certain imperfections, such as the inversion of the retina, arose due to evolutionary constraints. He also draws parallels with cancer biology, where evolutionary processes at the cellular level rapidly select for the fittest cells, which can be detrimental, as in the case of cancerous cells. In summary, he proposes that biology's complexity and seemingly imperfect structures arise from evolutionary "improvisation."
Professor Xiaofan Wang offers a perspective from cancer research, noting that studying the disruption of normal processes in diseases like cancer can provide insights into the unifying logic of biological organization. He points out that the metabolic competition between T cells and cancer cells during immunotherapy reveals the importance of understanding how cells' metabolic processes evolve. He connects this idea to the evolution of primates' ability to perceive red, where a single genetic mutation allowed a new functionality that provided a survival advantage. He believes that evolution, driven by environmental pressures, is a key force in shaping biological systems, leading to the complex hierarchical organization we observe today.
Q2: What drives the interplay between structure and function? How does evolution shape structure to optimize functional output?
Professor Yi Lin highlights that understanding the relationship between structure and function involves approaches such as genetic knockouts and biochemical experiments, where parts of the "machine" are removed to observe changes in function. She notes that there is still much to explore in this area, particularly with how we can better integrate information from different levels of organization (e.g., molecular, cellular, and higher systems) to understand how structures function. She emphasizes that evolution provides important insights into how simpler systems evolve into more complex ones, offering a way to look at the dynamics between structure and function from an evolutionary perspective. In the future, combining these insights with new techniques could help us grasp this interplay more effectively.
Professor Tian Xue suggests that the relationship of structure and function can be understood through the lens of both reductionism and new technologies, such as AI and big data. He proposes that AI could help analyze complex biological systems, providing insights into how structures and functions emerge from molecular and cellular interactions. He also emphasizes the importance of studying evolution, specifically comparing simpler organisms with more complex ones. By studying different species, such as primates and birds, researchers can better understand how structures like the fovea in the retina evolve to optimize function. Evolution, in his view, often works through incremental changes that provide survival advantages, optimizing function through a process of natural selection.
Professor Xiaofan Wang focuses on how the evolution of multicellular organisms, especially in relation to disease, shapes the interplay between structure and function. He discusses how the evolutionary transition from simpler organisms to more complex ones led to the development of complex signaling pathways for regulating growth and function. In the case of cancer, mutations often disrupt normal signaling pathways, making cells grow autonomously. He also refers to evolutionary changes that involve the reactivation of previously shut-down regenerative programs, such as in newts, which can regenerate limbs. This concept of "reprogramming" is central to understanding how evolution balances and reuses existing biological programs to optimize function. His thoughts suggest that understanding this balance could lead to therapeutic advancements, such as in immune system modulation for cancer treatment.
Q3: Can principles of organization guide new approaches to regulation and therapy? Might targeting the reversal of hierarchical organization offer new avenues for disease therapy?
Professor Yi Lin is optimistic about the potential of understanding biological organization to guide new therapeutic approaches. She emphasizes that to truly understand how structures relate to functions, we need to improve our resolution in studying structures, particularly at the molecular and cellular levels. By combining disease studies and evolutionary insights, along with the use of AI and other advanced techniques, it will be possible to create more comprehensive models of biological organization. She believes that as our understanding deepens, we will be able to develop more holistic therapies, instead of targeting individual molecules, particularly in cancer, by targeting the heterogeneity and diversity of cell types within tumors. In the future, she sees that biology may one day develop unifying principles, analogous to how chemistry uses its periodic table and physics uses fundamental laws, helping guide therapy development.
Professor Tian Xue highlights that while there are established principles in biology, such as those governing the nervous system and cellular communication, biology has not yet reached the level of predictability seen in chemistry or physics. He acknowledges that AI and data collection technologies may one day enable us to simulate biological systems, creating "virtual cells" or "virtual multicellular organisms." These simulations could potentially offer predictive insights, helping to identify missing elements in biological systems, just as the periodic table has done in chemistry. Although biology does not yet have a unified set of principles like those in other sciences, he is hopeful that advancements in AI and data-driven models could eventually provide predictive power in understanding and addressing disease.
Professor Xiaofan Wang also sees great potential in using simulation and AI to predict and understand disease processes that are difficult to study directly in humans. He discusses the challenge of studying complex diseases like dementia, where the effects might not manifest until many years later. By collecting data and using AI-driven simulations, it may be possible to model pathological processes and identify ways to intervene before symptoms appear. He emphasizes that with sufficient data and computational power, these models could offer new insights into disease mechanisms and provide novel avenues for therapy, compensating for the challenges of studying real human organisms directly.
Conclusion
This session provided a comprehensive exploration of hierarchical organization in biology. The discussions, led by Professors Lin, Xue, and Wang, underscored the intricate connections between molecular dynamics, cellular functions, and organismal behavior. A key takeaway is the pervasive role of dynamic self-assembly and regulated spatio-temporal control across biological scales. The webinar highlighted that understanding these unifying principles is not merely an academic exercise but holds significant promise for guiding future research and developing novel therapeutic strategies, particularly in addressing diseases linked to organizational dysregulation. The session successfully fostered a deeper appreciation for the complexity and elegance of biological systems and the potential for interdisciplinary approaches to unravel their mysteries.
With special thanks to our event network partners:
