The M-Lab is a basic science and translational research laboratory. The vision of The M-Lab is to translate basic research findings into clinical research aimed at improving cancer diagnosis and treatment. The strategic focus is two fold
Research Line 1 : targeting the tumour microenvironment
Research Line 2 : Clostridium mediated Therapy
Clostridium species are a crucial component of the healthy human gut. Members of this genus have been shown to assist colonocyte metabolism, induce regulatory T cells - especially as multi-species communities - and produce neuroprotective antioxidants (Figure 2). They are one of the two numerically predominant genera of the human gut. Their ability to produce spores not only allows them to cross the gastric acid barrier after oral consumption, it also renders the shelf-life of probiotics a non-issue. Clostridial spores are immensely robust, with the capacity to survive extreme temperatures, radiation and desiccation, while retaining the ability to restore active growth almost indefinitely.
Over the past 10 years, researchers have made a quantum leap in there development of molecular tools to study clostridia. Using CRISPR-Cas9 and its variants, the deletion or addition, up- or down-regulation of nearly any DNA sequence in the bacterial genome has become possible. This opens the way for chromosomal expression of reporter systems and exogenous products (e.g. cytokines such as IL15, chemokines, antigens…) without the disadvantage of antibiotic markers that can be transferred to other gut inhabitants or into the environment.
The M-Lab utilises a CRISPR-Cas9 gene editing vector for the addition or deletion of sequences to/from the bacterial chromosome in a range of Clostridium species. My team was instrumental in the application of CRISPR-Cas9 technology to engineer Clostridium sporogenes to secrete biologically active IL-2, and was previously involved in creation of the Clostridium-Directed Enzyme Prodrug Therapy (CDEPT) (11, 12). This uniquely engineered strain will serve as a platform to further exploit other immune modulators in this species and others.