Evolution

Perhaps the most unique and fascinating aspect of biology, among all natural sciences, is that the degrees of freedom – both their identity and number – are always in flux. Not only do genotype, phenotype, and environment co-evolve (possibly with no end!) in a fixed space, the dimensions of these spaces are also changing as new functions emerge, new interactions become a possibility, and so on. We are interested in these dynamics – in theory, simulation, as observed in natural history, or through experimentation – and the relationship to the apparent inherent bias towards complexity and diversity. A particular focus at the moment is to understand how selective pressures become coupled into “collective modes” when physical laws and biological constraints interact with the requirements for reproduction.

The limits of biological experimentation

Our longest-standing line of work plays around with a connection between biological organization, fundamental principles of high-dimensional statistics, and experimental design. Here’s the idea: Complex living systems tend to be highly organized. When we collect high-content, high-throughput data on these systems, this organization manifests in a substantial amount of statistical structure. Statistical theory and algorithms (mostly related to compressed sensing) allow us to exploit that structure through highly efficient “compressed” experiments with wacky designs, where each observed experimental outcome corresponds to a linear combination of conventional experimental outcomes.

Canalization of developmental trajectories

One of the most fascinating concepts in biology is the idea of canalization: dynamic processes, especially during development of multicellular organisms, are “canalized” to robustly follow the same trajectory and produce the same output, even in the face of environmental and genetic perturbation. We are interested in a deeper understanding of canalization: identifying canalized paths “hidden” in high-dimensional space, understanding how each path is triggered and regulated, and understanding how evolution “carves out” these canals in the first place.

At the moment, much of our work is focused on technical fundamentals, especially the reconstruction of cellular trajectories using single-cell “RNA velocity” measurements. We also have a growing interest in the early evolution of cellular differentiation in complex multicellular systems, the nature of genetic and phenotypic variability, and genetic assimilation.