How do bacteria cells know how fast they are growing?

A chemical signal synchronizes a cell’s biological engines with its growth, just as a broadcast signal synchronizes radio clocks worldwide with the rotation of the Earth. But while the radio signal is itself set by a time standard, it is unknown what sets the biological growth rate signal. We are working to identify what controls the cell-synchronizing signal to understand how it is itself set by the growth rate. Discovering the mechanism of growth rate synchronization will guide the design of new antibiotics against drug-resistant bacterial infections.

Producing antibacterial compounds in bacteria

Microbes that produce antibiotic compounds are ubiquitous. A few of these organisms are used to produce antibiotic on an industrial scale. Unfortunately for us, most antibiotic-producing microbes do not produce sufficient quantities for use in an industrial setting, and cannot be easily manipulated to increase production due to a lack of genetic engineering tools. As a result, many useful antibiotics are instead synthesized chemically, an expensive process that often generates toxic byproducts. We are interested in producing antibacterial compounds within genetically-tractable, fermenter-friendly bacterial hosts. We will overcome the obvious barrier of toxicity to the host organisms by safely deactivating antibiotic targets while maintaining the metabolic activity of the host.

Listening to a bacterial fire alarm

For the past several decades, biological research has focused on transcriptional control of cellular physiology. However, bacterial metabolism is also controlled by small molecules such alarmones, which directly regulate enzymatic activity. Enzymes involved in translation, DNA replication, and phospholipid biosynthesis can all be switched on and off these alarmone molecules. We have mapped some of the metabolic consequences of growth inhibition by one of these alarmones, revealing an extensive post-translational network of metabolite-protein interactions. We are interested in developing tools for observing metabolite-based control using fluorescence microscopy.

How plug and play is biology?

Thanks to the explosive growth of genome sequence data, we have at our fingertips a huge variety of genes that code for enzymes with countless enzymatic activities. With trivial genetic engineering techniques, these enzymes can be assembled into synthetic pathways that can transform bacterial cells into factories for valuable chemicals. However, not all enzymes can maintain activity after being transplanted into a new host. We will address the question: What determines if an enzyme will maintain its function when expressed in a new organism? In other words, how “plug-and-play” are enzymes and bacterial species?