Single cell responses to environmental changes

Individual cells can exhibit distinct behavior

We often think of a population as being uniform in behavior and appearance. However, individual, genetically-identical cells can exhibit remarkably distinct behavior compared to the population average. This difference in behavior could be due to spontaneous genetic mutation, or through non-genetic differential gene expression.

An example of the latter are “persister” cells. In a bacterial population, a small portion of cells enter a non-growing state, which allows them to survive hostile environmental conditions. For instance, persister cells are less susceptible to antibiotics, and can continue to grow after the antibiotic is removed. This behavior allows the population to survive, making bacteria incredibly resilient.

However, these findings also have direct consequences for human health, the environment, and industry. Persister cells can cause chronic infections which recur once treatment is stopped. In biotechnological applications, differences in cellular metabolic processes can detrimentally affect yields through the appearance of cells which enter a “non-” or “low-“producing state. Hence, understanding what causes a cell to enter this persistent state is important in developing ways to circumvent this behavior.

Microscopy allows the local environment to be quantified

Cells are affected by their local microenvironment, including nutrient levels, signaling molecules and physical interactions with neighboring cells. However, in many single-cell experiments, these effects are ignored or lost during sample preparation. In comparison, optical microscopy allows cells to be observed natively thereby preserving the information around each cell.

My current research on this topic is to develop new methodology and software to understand how individual cells are affected by their surroundings. My goal is to use this information to develop new models to explain why some cells behave differently compared to the rest of the population.

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