Research Insights

A grand challenge is how cellular clocks in organisms, tissues, and cells become synchronized. The focus here will be initially on understanding the synchronization of cellular clocks in filaments in a model fungal system, Neurospora crassa. The core clock mechanism genes wc-1, wc-2, and frq have homologs in flies and mammals but are in single copy, and the clock in tissues called hyphal filaments serve as a model for the clock in tissues in other eukaryotes. There are two principal theories for how clock synchronization arises; (1) through a shared quorum sensing signal in the media between cellular clocks; (2) through cell to cell contact and communication. The goal of this proposal is to understand the synchronization of biological clocks between filaments in N. crassa. An interdisciplinary team from genetics, engineering, physics and biochemistry will tackle this challenge. Task 1: We will develop novel microfluidics platforms to measure phase synchronization of biological clocks on a controlled number of living N. crassa filaments. Task 2: We will develop and identify models of clocks in filaments using novel ensemble methods from Physics. Task 3: We will also identify and test signaling molecules that may be responsible for the synchronization by a newly developed method of Continuous In Vivo Metabolism-NMR (CIVM-NMR) biochemistry. Collective behavior is a new field of study outside the boundaries of existing disciplines. The project is transformative because it examines the origin of the clock system by pushing the scale of measurements on the clock to single clock mRNAs. We will use CIVM-NMR to link metabolites with a quorum sensing signal for the clock. We propose the following convergences: (1) identification of metabolite(s) to explain the origin of circadian rhythms in single cells; (2) a physical theory of the clock in filaments identified by methods from statistical physics; (3) and explaining the origin of the clock in the phase synchronization of single filaments. The clock is pervasive in its effects on genes to ecosystems. (1) It impacts the health of animals and plants and is being engineered for the timed delivery of biologicals, the development of algal bioreactors and crop improvement. (2) The new methods for studying cell-cell synchronization have a direct relevance to the collective behavior of animals, such as marching locusts and their control as agricultural pests. (3) The clock through its light-entrainment capability has a direct impact upon the daily transcriptome dynamics of marine bacterial assemblages and hence may impact carbon cycling in marine ecosystems. Education and outreach activities are designed around the research focus of this project, biological clocks and their synchronization. (1) An interdisciplinary research-centered course, Clock Collaboratorium, will be developed. (2) Undergraduate research projects will be developed with the central theme of biological clock and used in two NSF REU site programs. (3) we will build a collective behavior community of scientists through a Gordon Research Conference in Collective Behavior.

Funder: NSF 

Amount: $1,324,119 

PI: Jonathan Arnol, Franklin College of Arts and Sciences, Department of Physics and Astronomy