This is a collaborative research proposal between the US PI (Dr Erel Levine, Harvard University) and Dr Joel Stavans of the Weizmann Institute, Israel. The bacterial cell is composed of a single compartment within its membrane, which often leads to the assumption that the bacterial cell is a well-mixed homogeneous environment. However, evidence has accumulated that many processes in the bacterial cell are spatially organized, and that some molecules, including messenger RNAs (mRNAs) of some genes, exhibit clear patterns of distribution that are non-random. This project addresses how patterns of spatial distribution can contribute to and affect function; how they are regulated; and how distribution patterns affect interactions between molecules in the living bacterium. Undergraduate and graduate students will be trained and gain hands-on experience in both the experimental and theoretical aspects of the proposed project. The collaboration adds an international dimension to this training as well as to a high-school student research network.
Fundamental principles of the dynamics of biological control in the crowded environment of the cell will be uncovered using advanced microcopy techniques, experimental methods of molecular systems biology, and theoretical modeling. The following specific issues will be addressed: 1) the localization of transcripts that are targets of sRNAs, and the manner in which this localization is modulated by sRNAs 2) the mechanistic roles of sRNA-target interactions in localization-dependent sRNA regulation and 3) the implications of sub-cellular localization for the regulatory properties of network motifs. This information will facilitate the development of predictive models of gene regulation that can explain cellular behaviors and direct the design of synthetic circuits.
This award is supported jointly by the Division of Molecular and Cellular Biosciences and the Division of Physics (Physics of Living Systems).