Collaborative Research: Multidimensional single-cell phenotyping for elucidating genome to phenome relationships

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Abstract

The aim of this project is to develop methods and apply them to better understand how cells can optimally perform more than one task simultaneously, such as to grow and to synthesize biofuels at high quantities and efficiently. These findings are expected to accelerate ongoing efforts that employ biological systems as factories to produce high-value chemicals, and, thus, contribute to a more sustainable bioeconomy. This project will also offer exceptional training opportunities to high school and undergraduate students underrepresented in science, with a focus on transferring the mathematical rigor of physical and engineering sciences to biology. Further, this project is highly interdisciplinary, thus offering exceptional training opportunities to graduate students towards professional careers that address multifactorial societal needs. Systems biology has greatly improved our ability to program cells to perform a specific task. As the number of desired tasks increases, however, the complexity of biological systems restricts our ability to program or explore the foundation of cells that optimally perform multiple tasks simultaneously. This project will address this challenge via transformative microfluidic screening of combinatorial mutant libraries with single-cell resolution. Single-cell resolution will critically enable the selection of mutants directly from growing cultures, as well as quantify cellular noise. By applying the proposed method to an important biofuel platform and by combining the experimental results with genome-scale metabolic models, the project will generate fundamental knowledge on the genome-wide origins of multidimensional phenotypic traits and cell-to-cell phenotypic heterogeneity. This project is jointly funded by Systems and Synthetic Biology Cluster of the MCB Division and the Established Program to Stimulate Competitive Research (EPSCoR). 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.