Forms and Contexts: Pursuing a multi-scale understanding of genome function

In this talk, I will discuss the challenges and opportunities in integrating perspectives from physics and biology to understand genome organization across multiple scales. Although my research centers on single-cell and spatial transcriptomics rather than subnuclear genome folding, I will share thoughts on how insights from different scales can inform one another. Coming from physics and later transitioning into genomics, I have come to appreciate how biological complexity resists simple reduction. While physics succeeds in its quest for fundamental laws, biology requires patience to embrace its endless forms of complexity. The macro does not arise as a linear aggregation of the micro; each scale of organization may operate under its own emergent rules, shaped by evolutionary and developmental contingencies. I will use highly multiplexed in situ measurements of gene activity during spermatogenesis to illustrate how we can probe interaction rules across adjacent scales—from cells to cell communities to tissue-level functional units. Ultimately, a deeper understanding of the somatic unfolding of genome function will require an integrative mindset that blends the physicist's hunger for unifying principles with the biologist's appreciation for hierarchy, local contingency, and context.