NSF Postdoctoral Fellowship in Biology FY 2020: Proportional assembly of intracellular structures

Mcinally, Shane G, Waltham MA

Investigators

Abstract

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2020, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment and Phenotypes. The fellowship supports research and training of the fellow that will contribute to the area of Rules of Life in innovative ways. Every cell must measure and control specific aspects of its size, and the size of its internal components, yet how this is achieved remains an unsolved problem. Proper function of different cellular structures, including mitochondria, which produce energy, and components of the cytoskeleton, a rigid internal structure that helps cells keep their shape, depend on different aspects of their size. These structures are also dynamic, as they continuously replace their molecular components. To understand how cells control the size of these structures, the fellow will explore new mechanisms of size control by developing quantitative models that describe these aspects of cellular design. This research will uncover the mechanisms cells use to control and scale the sizes of their internal parts, which is a universal engineering challenge faced by all living systems. Another major goal of this project is to expand interdisciplinary scientific education of graduate and undergraduate students through the Quantitative Biology Research Community (QBReC) at Brandeis University. The goal of this research is to understand how cells assemble subcellular structures that are proportional to their linear dimensions. Current models of cellular size control cannot explain this critical aspect of cellular behavior. To address this problem, the fellow will perform research that is broken down into two aims. In the first aim, quantitative microscopy methods will be used to compare the scaling of actin cable lengths in yeast cells with natural and genetically induced changes to cell size. The fellow will also test the role of cell shape in determining actin cable lengths in mutant cells with elongated morphologies. In the second aim, quantitative measurements will be made of the different rates that govern actin cable assembly. The fellow will acutely deplete or activate different cable assembly proteins, while at the same time perturbing cell size and shape. A key goal will be to determine which rate(s) confer scaling of actin cable length with cell size. In both aims, the fellow will use super-resolution microscopy and develop new quantitative image analysis methods. In conjunction with the experimental work, the fellow will be building and testing biophysical models of self-organization of actin cables in yeast. The models will in turn fuel new experimental work on the cables, as well as provide mechanistic insights into the scaling of other self-assembling structures in cells. In addition to the formal training in theoretical modeling, the fellow will receive training in grantsmanship, project design and interpretation, manuscript writing, teaching, and scientific communication. The fellow will also mentor students from a range of scientific backgrounds through the Quantitative Biology Research Community (QBReC) at Brandeis University. 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.