BII: Mechanisms of Cellular Evolution

By integrating across disparate fields in the life, physical, and mathematical sciences, this institute is designed to yield a mechanistic understanding of evolutionary processes. The broad goal is to decipher the general rules by which evolution proceeds at the cellular level, while simultaneously engaging in research and educational activities to help build a formal field of evolutionary cell biology.

An immediate goal is to determine how aspects of cellular evolution across the Tree of Life are governed by: internal cellular constraints, the laws of biophysics and bioenergetics, and the genetic features of populations. Specific projects include: a quantitative survey of how cells apportion their energy budgets into a range of structures and functions; the development of theory to understand the paths that are open vs. closed to evolutionary modification in various lineages; comparative analyses of the structures and functional capacities of the major molecular machines in cells; and the use experimental laboratory populations of microbes to determine how cells respond evolutionarily and developmentally to temperature and nutritional challenges.

By identifying key details at the cellular level, the institute will greatly expand our understanding of mechanisms underlying evolutionary processes, while also revealing rational strategies for engineering microbes with novel beneficial functions and for eradicating harmful pathogens. A range of activities, including student-exchange programs with collaborators, annual workshops, development of educational materials, and establishment of an atlas of cellular information will expand the reach of the institute to national and international levels.

Over its duration, the institute is expected to connect with a wide range of integrative research and educational foci, with a common goal of bringing a new dimension of evolutionary biology to cell biology and vice versa. The research starts with several multifaceted projects, the first using comparative genomics, spatial intracellular proteomics, ultramicroscopy, and bioenergetic analyses to provide a broad phylogenetic overview of cellular features and the relative costs of constructing and operating them.

The second project draws from empirical observations to build quantitative theory for the mechanisms by which cell-biological features evolve, in particular how the paths open to evolutionary exploitation vary phylogenetically. This project also takes a structural-biology approach to explore how major cellular complexes with essential and highly conserved functions, e.g., ATP synthase and ribosomes, are nonetheless free to diverge evolutionarily.

The third project capitalizes and expands upon established long-term evolution experiments with microbes to evaluate the genomic changes that arise in response to selection on cell size and growth rate over gradients of nutrient, temperature, and population-genetic conditions, and seeks to understand why the phylogenetic scalings of growth rates and cell sizes have opposite directionality in prokaryotes and eukaryotes. The integration of these projects will reveal the Rules of Life at the cellular level and establish mechanistic explanations for them from first principles.

Involving work from scientists from diverse backgrounds, the collaborative projects build outwardly from the local to the national/international level.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.