Our lab studies programmed cell death, a process crucial for tissue development and keeping us healthy.
We use protein crystallography to visualise molecules in atomic detail. This is providing insights into the proteins that regulate programmed cell death and guiding the development of drugs that can target these proteins in diseased cells.
Permeabilisation of the outer mitochondrial membrane is a key step in the programmed cell death pathway of apoptosis, this releases factors that result in the destruction of the cell. The Bcl-2 family of proteins regulate this event, our studies have revealed steps in the conversion of family members from inert monomers to membrane permeabilising killers (Czabotar Cell 2013, Brouwer Mol Cell 2014, Cowan NSMB 2018, Birkinshaw Mol Cell 2021) and have guided the development of agents to modulate Bcl-2 family activity in diseases such as cancer (Lessene NCB 2014, Brouwer Mol Cell 2017, Birkinshaw Nat Comms 2021, Roy JMC 2021).