How does a cell orient in response to a chemical cue? This basic problem is at the core of how cells interact with their environment. Indeed, the ability to move towards the source of a chemical gradient underlies behaviours as diverse as feeding, identifying a foreign invader or building interconnected cellular networks. Furthermore, chemo-orientation forms the basis of gamete recognition, and is thus critical for genome diversification through sexual reproduction.
This proposal makes use of one of the simplest eukaryotic models, the fission yeast S. pombe, to systematically dissect the mechanisms of gradient detection. Gradient sensing occurs during sexual reproduction in a speed-dating process for mate pairing, where dynamic cortical polarity patches secrete pheromones and become stabilized in response to those produced by the other mating type. Chemo-detection depends on a minimal kit of conserved eukaryotic proteins, suggesting that a complete understanding of gradient decoding is possible. We will work towards this goal through four specific aims:
1. to establish the rules of gradient decoding, using unbiased image analysis and caged pheromones;
2. to define the architecture of the communication site, by super-resolution and correlative light-electron microscopy;
3. to probe the molecular regulation of cellular speed-dating, which we hypothesize consists of a spatial decoder and dynamic oscillator;
4. to reveal natural modifiers of speed-dating for mate selection, by exploiting the diversity of wild strain isolates.
By combining advanced live and correlative imaging with optogenetic, genetic, biochemical and genomic methods, this project will bring a conceptual and molecular understanding to the problem of gradient decoding. Due to the ancient and fundamental nature of gradient orientation, our discoveries will have impact on several fields of research, including those of immunity, wound healing, development, sexual reproduction and evolution.
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