What are we about?
We are curious to learn how bacteria work, and in figuring out ways to make bacteria (even more) useful. We have both fundamental and applied projects, and are always happy to pursue research in new and interesting directions.
How do growing bacteria cells know how much membrane they need to make?
How do cells grow without breaking their membranes? Cells build and expand their outer layers at a pace that is somehow coordinated with growth. Understanding how cells synchronize growth with the metabolism of membrane synthesis will answer one of the oldest and most elusive questions in biology. Our goal is to understand how a model bacteria species (Escherichia coli) controls the rate of membrane assembly from metabolites. By profiling concentrations of intermediates in the membrane assembly pipelines, we identified the enzyme (PlsB) whose activity is modulated to ensure coupling of membrane synthesis with growth. Our next step is to determine the specific growth-related cue that directly controls PlsB activity.
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 recently showed how to overcome the obvious barrier of toxicity to the host organisms by safely deactivating antibiotic targets while maintaining the metabolic activity of the host.
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? We are currently exploring this question as part of the IronPlugNPlay Consortium.
What is listening to a bacterial fire alarm?
Bacterial metabolism is partly controlled by small molecules such alarmones, which appear during stress or starvation and can directly regulate enzymatic activity. Enzymes involved in translation, DNA replication, and phospholipid biosynthesis can all be switched on and off by one of these alarmones, the small molecule guanosine tetraphosphate (ppGpp). However, as ppGpp is present at low levels even in the absence of strees or starvation, it's unclear when the enzymes pay attention to ppGpp. We are seeking to determine whether even low concentrations of ppGpp are able to modulate membrane synthesis or protein translation. We hope to clarify whether ppGpp is truly a fire alarm that brings growth to a near-halt, or whether the global reach of ppGpp enables it to act as a chemical signal that synchronizes the various assembly lines that build a cell.