From pattern to function: eco-evolutionary representations of complex spatial structure for the new era of spatial biology

NIH RePORTER · NIH · R35 · $380,500 · view on reporter.nih.gov ↗

Abstract

Through innovations in both imaging techniques and the ability to process these images at scale, high- resolution imaging is transforming the eld of molecular biology, yet its power has yet to be fully utilized for asking questions in evolutionary biology. Just as demographic surveys can reveal more or less densely populated areas where, for example, a contagious disease may spread at di erent rates, these imaging datasets can help us quantify cellular and molecular patterns of spatial variation and understand how this variation a ects rates of evolution, by impeding or accelerating the spread of new variants through the population. My research program, at the interface of computer vision and evolutionary biology, is exploring how molecular and cellular communities spatially organize, and how the resulting spatial topologies can be generated, stably maintained and further shape the outcome of the evolutionary process. What are spatial topologies that act to amplify the selective advantage of new mutations in the pop- ulation, versus structures that dampen the force of selection and slow down rates of evolution? We build theoretical evolutionary models that explore how the rate of evolution is shaped by complex spatial struc- ture and nd the relevant spatial features for evolutionary ampli cation or selective suppression. We link these theoretical population genetic models to high-resolution imaging datasets and study the resulting spatial architectures. This allows us to go beyond simply describing patterns of cellular or molecular spatial variation, and enables exploration of the generative processes, as well as of the evolutionary trajectories of the system. Beyond the purely theoretical interest in these questions, understanding the role of spatial structure in shaping the mode and tempo of evolutionary dynamics is particularly timely because, by using modern microfuidics and organoid technologies, we can start building population structures that control the topol- ogy and migration patterns of a molecular or cellular population, amplifying the selective bene t of chosen mutations, boosting the ability to nd optimized protein complexes for medical or industrial applications, or as a screening tool for faster replicating pathogenic variants.

Key facts

NIH application ID
10501428
Project number
1R35GM147445-01
Recipient
CARNEGIE-MELLON UNIVERSITY
Principal Investigator
Oana Carja
Activity code
R35
Funding institute
NIH
Fiscal year
2022
Award amount
$380,500
Award type
1
Project period
2022-09-27 → 2027-06-30