Coordinating the life cycle of bacteria

In the Mera Lab, we are passionate about bacteria, particularly as it relates to the sophisticated molecular choreography that guides their growth. We combine bacterial genetics, biochemistry, and high-resolution imaging in order to examine the progression of the cell cycle at the molecular and cellular level. In order to best accomplish our goals, we use the genetically tractable bacterium Caulobacter crescentus whose cell cycle can be easily synchronized to enable fine temporal resolution of each cell cycle event. Our work has also expanded to include Helicobacter pylori, the causative agent of peptic ulcers and strongest risk factor for the majority of gastric cancers.

The following are the three major areas of research currently being investigated in our lab:

• Communication is complicated… just ask a bacterium. Maintaining the integrity of the genome is essential to the survival of all bacteria. This maintenance is accomplished through major cell cycle events such as chromosome replication, segregation, and proper timing of cytokinesis. Although replication, segregation, and cytokinesis have been extensively studied in bacteria, our understanding of how these processes are temporally and spatially coordinated remains incomplete. Using a systemic approach, we have identified new communicative processes that keep the onset of chromosome replication and the onset of chromosome segregation highly interconnected. We have shown that a key regulator of chromosome replication can promote segregation independently of chromosome replication. Remarkably, these two mechanisms are also communicating in the reverse direction. A key regulator of chromosome segregation can also promote the onset of replication independently of chromosome segregation. Our work is exposing the complex and multidirectional communicative systems involved in coordinating the progression of the cell cycle. Mistakes in this essential coordination of events can be lethal for the survival of the cell. As such, targeting the molecular networks involved in coordinating cell cycle events in bacteria represents an attractive target for antibiotic development.
  
  
• Coexisting with a changing environment. Bacteria are masters at adapting and surviving sudden changes in their environment. We are interested in figuring out how bacteria integrate information from the environment into the molecular networks that drive the forward progression of the cell cycle. Our work focuses on two environmental cues: nutrient availability and presence of stressors such as antibiotics. We have found that cell size regulation and timing of chromosome replication are interconnected, a connection that is influenced by nutrient availability. This is interesting because the molecular factors responsible for regulating cell size in bacteria and the mechanism that coordinate cell size regulation with the progression of the cell cycle remain unclear. Regarding antibiotics, we have isolated mutants of Caulobacter crescentus that exhibit multidrug resistance and display developmental problems. We are currently working out the molecular network that links cell shape regulation and ability to resist toxic compounds. Our long-term goal is to build a model that incorporates the full repertoire of factors involved in orchestrating the progression of the cell cycle in bacteria. The development of such a model has the potential to be transformative in our ability to control bacterial growth.
  
  
• It’s a matter of survival. Bacteria, especially soil bacteria, are amazing chemists that synthesize various powerful chemical weapons to efficiently kill the competitors. The intriguing question is how these synthesizers protect themselves from those nasty compounds. This is a collaborative project with Dr. Chu Young Kim (Biochemist and Crystallographer) from the University of Texas – El Paso. We have identified a novel protein that looks structurally like a DNA repair protein and yet this protein has the capability of making cells resistant to antibiotics that intercalate DNA. The DNA repair protein and the antibiotic resistance protein look pretty much identical except for one missing domain. What is fascinating is that the difference of this relatively short domain prevents these two proteins from complementing each other’s function. We are currently investigating the mechanism that this DNA repair-like protein utilizes to recognize DNA intercalators and overcome their toxicity.

Beyond science

Aside from the excitement of scientific discoveries, members of the Mera lab are committed to sharing the fun of science with the community at large through various outreach programs. In the past, we have established science activities and culture-centered programming aimed at increasing participation and engagement of disadvantaged populations in STEM fields. One particularly exciting program that we founded in collaboration with others was a program called Fostering STEM in Las Cruces. The Fostering STEM program worked with children enrolled in the foster care system in developing science themed activities. The goal of the program was to inspire a love of science and inquiry that would lead into further study in higher education.