A close look at redox signalling from mitochondria using small molecule chemistry

We used to believe that the reactive oxygen species (ROS) produced by mitochondria were always damaging. ROS certainly contribute to serious health conditions: cancer, cardiovascular disease, heart failure, stroke and neurodegeneration. However, we are beginning to understand that ROS are part of a complex signalling system that ensures healthy functioning of cells. Malfunctioning of this redox signalling network causes the serious health problems. Unfortunately, we do not yet know how this system works and so cannot correct it when it goes wrong.

We hypothesise that it matters where, when and how ROS are generated. The exact location is critical, right down to which side of which membrane in which organelle. For this reason, we will design and use organic synthesis to make novel small-molecule probes that attach themselves to very specific sites in and around the mitochondria and report the signalling events.

The research will involve molecular design with consideration of reactivity and physicochemical properties, multi-step organic synthesis including the handling of moisture and air-sensitive compounds, chemical characterisation of new compounds (NMR, MS, IR, UV-Vis, fluorescence) and validation of probes in vitro, in isolated mitochondria and in cells.