Reprogrammed yeast cells enhance drug delivery precision

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Researchers from the Yong Loo Lin School of Medicine (NUS Medicine) have developed a novel way to engineer yeast (Saccharomyces cerevisiae) to create microbial communities that can perform complex tasks and self-regulate their composition in response to external signals.

By reprogramming how yeast cells switch types, the team enabled these micro-organisms to form cooperative groups that can perform complex tasks and self-regulate their composition based on external signals. These engineered yeast cells have the potential to help transform personalized health care by delivering tailored treatments that adapt to a patient's condition in real time.

This approach could lead to more effective therapies with fewer side effects, paving the way for significant advancements in medical treatment while also significantly enhancing the efficiency, sustainability, and scalability of biotech applications. The study is published in the journal Nature Communications.

Traditional microbial biotechnology has focused on single-cell organisms, limiting their ability to handle complex tasks. The NUS Medicine team re-engineered yeast cells to mimic natural ecosystems, enabling them to divide into two specialized types that work together synergistically. These synthetic microbial communities can autonomously adjust their population composition in response to environmental stimuli, making them ideal for tasks undertaken in precision medicine or therapeutic applications in the human gut.

The yeast cells act as microscopic factories, capable of producing therapeutic compounds or breaking down complex substances into simpler, usable forms. By responding dynamically to disease markers—small molecules that accumulate in the body during illness—the yeast adjusts its structure and activity to deliver just the right amount of therapeutic compounds. This smart programming ensures the yeast only produces what is needed, reducing waste and increasing precision.

"This artificially engineered smart yeast could revolutionize how microbial communities are controlled for health purposes. As the communities can independently split into different types of cells that work together, it allows them to divide tasks and share the workload, alleviating the burden it places on the cells," said research team leader A/Prof Matthew Chang, Director of the Synthetic Biology Translational Research Program at NUS Medicine and NUS Synthetic Biology for Clinical and Technological Innovation.

"For example, in the gut these yeast cells can adjust their balance and activity based on health signals, like disease markers, without needing any manual adjustments. This approach reduces stress on the cells and allows for precise production of helpful compounds, making it useful for flexible, targeted therapies in treatments and thus potentially reducing any side effects and improving treatment efficacy."

The research team is now fine-tuning their results, with a focus on optimizing how the yeast communities adapt their actions in response to various disease markers. They will then explore the efficacy of using this autonomous system to produce health-conferring molecules for treatment of specific diseases.

More information: Yu Chyuan Heng et al, Tunable cell differentiation via reprogrammed mating-type switching, Nature Communications (2024). DOI: 10.1038/s41467-024-52282-w

Journal information: Nature Communications

Provided by National University of Singapore