Physical Biology: From Gene Regulation to Living Matter

# Viruses, ecology, and the search for quantitative biological laws Watch the video first. Use this companion to revisit the reasoning and its evidence limits. A typical tailed phage is a protein shell, the capsid, packed with its genome, attached to a tail that injects the DNA into a bacterium. Inside, the phage can take over the cell's machinery to make new phages. One approach is biology by the numbers. In 2018, Gita Mahmoudabadi and Rob Phillips compiled thousands of complete viral genomes and measured simple quantities across them: genome length, gene density, noncoding fraction, and categories of gene function. Numbers also expose ignorance. More than half the proteins of double-stranded DNA phages were annotated only as hypothetical or putative. And each of about nine hundred such genomes encoded at least one protein resembling a bacterial one, a hint of shared gene pools. To find viruses in the wild, researchers sequence everything in a sample at once: metagenomics. Reads from many organisms are mixed together, complete viral genomes are hard to assemble, and many viral sequences can't yet be linked to a known host. In 2023, Tadmor, Mahmoudabadi, Foley and Phillips used a marker gene shared by many tailed phages, the large terminase subunit, to define phage families. Across six hundred ninety metagenomes from one hundred three people, they found families shared across humans, distinct community structures in different mouth and gut habitats, and most families persisting over about seven months. A 2024 follow-up sequenced a small region of one terminase family in about seven hundred mouth samples from about a hundred people on several continents. Each person's pattern of variants, a phageprint, differed between individuals, except partners, and was generally stable in ten people tracked for a month. Machine-learning models told individuals apart with high precision and recall. Keep the claim narrow. This is one phage family, in the mouth, in about a hundred people, mostly over weeks. It is a research result about individuality, not a biometric technology. And association isn't function: knowing which phages occur where does not, by itself, establish what ecological role they play. Step back. Gene regulation asks: can molecular binding energies predict cellular output? Fidelity: what does consuming energy let biology do that equilibrium cannot? Active matter: how does microscopic energy use create large-scale motion? Viral ecology: can quantitative measurements reveal organizing principles in enormous diversity? All four share one strategy: count, model, predict, measure, revise. The models are deliberately simple; physics doesn't reduce biology to a few equations. And when a prediction fails, the failure points to the assumption to fix. ## Evidence guide PHILLIPS-LAB PRIMARY RESULT: comparative viral genomes, metagenomic phage-family tracking, and a dataset-specific oral classifier connect counting to hypotheses. EXPERIMENTAL MEASUREMENT here means observed genomic data, not an intervention establishing ecological cause. Many hosts remain unknown. Association is not causal ecology; the classifier is not a universal biometric system. Sources: [mahmoudabadi2018], [tadmor2023], [mahmoudabadi2024]. See the course bibliography and claim audit.