Bacterial cell cycle group

Anders Løbner-Olesen laboratory (ALO lab); Bacterial cell cycle group. 

Visit "Upcoming events" for lab members exam dates, conferences etc.

The main research topic of the ‘Bacterial cell cycle group’ is the cell cycle control of DNA replication in bacteria, using the model bacterium Escherichia coli. We have described key aspects of the E. coli cell cycle control such as: the DnaA protein being limiting for replication, the role of Dam methylation in replication and global transcription, and the importance of cis-acting control regions. Recently we have widened our focus to include projects of applied and medical relevance, including but not limited to the development of antimicrobial compounds targeting especially the DNA replication machinery.

Our ongoing research areas are:

1a. Control of bacterial chromosome replication

In most bacteria, chromosome replication is initiated by DnaA. In Escherichia coli, the frequency of initiation is controlled by the availability of active initiator protein, DnaA^ATP. Recent data from our lab suggests an intimate coupling between both DNA precursor biosynthesis and energy metabolism and cell cycle control.

1b. DNA metabolism of persisting bacteria

Chronic infections caused by pathogenic bacteria represent a major health problem. It is thought that bacteria can become transiently multidrug tolerant without genetic transformation by adopting a “dormancy” strategy; i.e. forming persisters. Multiple processes dictate the formation of persisters. The onset of chromosome replication is the primary stage for regulation of the entire bacterial cell cycle. It is tempting to speculate that a blockage of DNA replication may constitute a switch between the growing and the sleeping state of bacteria. This research topic is in part funded by the Danish National Research and Novo Nordisk Foundations Centre for Bacterial Stress Response and Persistence (BASP; see “Current Grants”).

2. Development of antimicrobial compounds

In recent years, many bacterial pathogens have become resistant (or insensitive) to most of the current commercial antibiotics available. We have isolated peptides that inhibit growth of both Gram-positive and Gram-negative bacteria as partners of The Danish Centre for Antibiotic Research and Development,  University of Copenhagen Research Centre for Control of Antibiotic Resistance (UC-CARE) and most recently as co-founders of the Center for Peptide-Based Antibiotics (CEPAN; see “Current Grants”), funded by the Novo Nordisk Foundation Challenge Programme. In CEPAN we investigate the antisense antibacterial concept for potential antibacterial compounds targeting especially the DNA replication machinery in Gram-negative bacteria as well as elucidating the mechanism of action of leading novel compounds.

Please visit “Projects” for an orientation of ongoing research in the group.