Bacteria use various mechanisms to secrete proteins that will shape their environment. We are interested in the payload that these systems deliver, i.e., in their toxins; we want to identify new toxins and decipher their activities and targets. 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 antibacterial activities or virulence activities, respectively.
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, such as MIX-effectors and FIX-effectors. These effectors share conserved N-terminal domains that are fused to various toxin domains at their C-termini, including lipases, pore-forming toxins, nucleases, de-amidases, and many toxin domains of unknown function and targets. 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
We are mostly interested in vibrios, a family of marine bacteria that rule the oceans. Many vibrios are emerging or prominent pathogens of both humans and marine animals, and cause devastating losses aquaculture industries. We work on various Vibrio species (e.g., parahaemolyticus, coralliilyiticus, alginolyticus, campbellii, proteolyticus) and use various approaches to study their interactions with other cells. Although most of our work focuses on the antibacterial and virulence activities of Vibrio T6SS, we also study toxins delivered by other secretion systems.