Research
Bacteria use various mechanisms to secrete proteins that will shape their environment. We are interested in the payload these systems deliver, i.e., in their toxins; we want to identify new toxins and decipher their activities, targets, and dissemination mechanisms in bacterial populations.
Another area of interest in our lab is the mechanisms that allow these toxins to be directed for secretion by a specific secretion system. Ultimately, we use the knowledge we acquire to engineer novel antibacterial treatment strategies.
Currently, our main focus is on the type VI secretion system (T6SS). It is one of the most interesting bacterial protein secretion systems out there. This macro-molecular machine delivers toxins, called effectors, to the environment or directly into adjacent recipient cells, either bacterial or eukaryotic. Therefore, it mediates both antibacterial activities and virulence activities.
Developing novel antibacterial treatments
We use molecular and synthetic biology techniques to engineer T6SS-based platforms and toxins that will be used as novel antibacterial treatments. We are also identifying potential targets that can be used to develop new antibacterial drugs.
Identifying novel toxins and mechanisms of action
T6SSs deliver effectors that mediate antibacterial activities or manipulate eukaryotic cellular processes to the advantage of the pathogen. We are developing multidisciplinary methodologies to identify novel T6SS effector families. Using biochemical, proteomic, genetic, and bioinformatic approaches we study the functions and targets of these new effectors.
Polymorphic effector classes
Through proteomic and bioinformatic analyses, we identify widespread classes of polymorphic T6SS effectors. These effectors share conserved N-terminal domains that are fused to various toxic domains at their C-termini, including lipases, pore-forming toxins, nucleases, de-amidases, and many domains of unknown function . We study the mechanism of secretion of these modular effector classes, investigate the role of the conserved N-terminal domains in T6SS-mediate secretion, and identify toxic activities and targets of these effectors.
Dar et al, Marine Drugs, 2018
Mobile genetic elements
How do bacteria share toxins? We identify mobile genetic elements that move toxins between bacterial populations to understand the evolution of bacterial competition. We recently identified the Gamma-Mobile-Trio (GMT) system, which mobilizes genomic islands of >100kb into insertion sites containing diverse inverted repeat sequences. These GMT island have unique cargo and specialize in mobilizng antibacterial T6SS effectors and anti-phage defense systems.
Human, animal, and plant pathogens
We work on various model systems, including Vibrio, Aeromonas, and Pantoea species. We use various approaches to study their interactions with other cells. Although most of our work focuses on the antibacterial and virulence activities of the T6SS, we also study toxins delivered by other secretion systems.