Biological rhythms are a fundamental property of life, and even single cells can generate both cell cycles and circadian oscillations. Less well known but potentially just as ancient, cells also undergo metabolic oscillations, with metabolic activity cycling once but occasionally multiple times during a cell cycle. We do not know why these oscillations are there.
In this project, you will use a combination of microfluidics, time-lapse microscopy, molecular biology, and machine learning to study metabolic oscillations in budding yeast. The response of yeast to changes in nutrients is analogous to how our own cells respond to hormones, and many of the key signalling proteins are conserved. By characterising the metabolic rhythms of cells stressed by changing nutrients, relating this behaviour to cellular fitness, and comparing with the response of mutants, you will determine how metabolic oscillations enable cells to adapt to change.
You will combine microfluidic technology that we have developed to follow hundreds of single cells over time in changing environments with fluorescence measurements of the redox state of flavin molecules. Analysing your results with established machine-learning algorithms, you will determine if the metabolic rhythms before stress predict the success of the cell’s response to stress and which signalling molecules are responsible.
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