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Quantitatively deciphering a novel metabolic pathway triggered by sulfide gas

Project description

Sulfur metabolism in yeast

Hydrogen sulfide (H2S) is a gaseous molecule that serves as a signaling mediator in the maintenance of cellular homeostasis, limiting damage to tissues. Despite evidence suggesting its beneficial impact on the mammalian gut microbiome, little is known about the role of H2S in microbiology. The EU funded Yeast H2S Signalling project will investigate the sulfur metabolism pathway in Saccharomyces cerevisiae and delineate how yeast responds to H2S. The work will uncover how this metabolic pathway influences cell-cell interactions and fitness and generate quantitative tools for quantifying volatiles and their impact on microbial interactions.

Objective

Gaseous mediators are ubiquitous in biology. For example, hydrogen sulfide (H2S) signalling leads to cardioprotective effects in humans and is believed to be beneficial for the mammalian gut microbiome. However, gaseous mediators in microbiology are under-explored because quantification of volatiles is challenging. Here, I will investigate how the volatile metabolite H2S can mediate cell-cell interactions and trigger a hitherto unknown sulfur metabolism pathway in Saccharomyces cerevisiae. Conventionally, Met17 is believed to be the only enzyme that can assimilate H2S (generated from inorganic sulfate) into organic compounds, and hence essential for growth on inorganic sulfur sources. However, I observed that the met17 deletion mutant can in fact grow on inorganic sulfate, albeit only at sufficiently high initial cell densities. My preliminary analyses suggest that H2S accumulates in met17- cultures, and when it reaches a threshold, enables cell growth by triggering an alternative sulfur metabolism pathway. In this proposal, I will 1) quantitatively understand how the alternative pathway responds to H2S by developing a mathematical model of density-dependent growth in met17- populations; 2) uncover the novel sulfur metabolism pathway in yeast by using transcriptomics and genetics; and 3) investigate the contribution of this H2S-responsive pathway to the fitness of wildtype yeast using population dynamics analyses. My research will not only offer mechanistic insights into how hidden aspects of yeast sulfur metabolism may contribute to cell-cell interactions and fitness, but also provide quantitative tools for studying gas-mediated microbial interactions from an interdisciplinary perspective. Finally, the project will extensively train me in the synergistic interplay between experiments and mathematical modelling — a style I hope to establish in my future, independent research.

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Coordinator

UNIVERSITY COLLEGE LONDON
Net EU contribution
€ 212 933,76
Address
Gower street
WC1E 6BT London
United Kingdom

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Region
London Inner London — West Camden and City of London
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00