We aim to uncover the molecular choreography of bacterial cell envelope machinery, namely how protein complexes assemble, interact, and coordinate their activities to build and maintain a functional envelope. To achieve this, our lab pursues complementary projects spanning multiple resolution scales, from atomic-level structures to dynamic processes in living cells.
Our core projects include:
Resolving Protein Complex Cooperativity
Using classical protein biochemistry and structural biology approaches such as single-particle cryo-EM, we investigate the Tol-Pal system and its interactions with the peptidoglycan synthesis machinery. These studies reveal how key protein complexes cooperate to stabilise the outer membrane and maintain peptidoglycan integrity. We can see how the systems compensate in knockout strains to preserve envelope function and bacterial survival. This work may uncover new targets for disrupting bacterial envelopes and combating antibiotic resistance.
Localisation of Cell Envelope Complexes in Cells
We are developing advanced cryo-electron tomography (cryo-ET) methods, incorporating DNA origami and bacteriophages, to capture bacterial cell envelope protein complexes in their native environment. By visualising these complexes at molecular resolution inside intact cells, we aim to understand how proteins assemble and interact to coordinate envelope construction. Resolving the spatial organisation of envelope machinery bridges the gap between cellular imaging and molecular detail, which is essential for elucidating molecular mechanisms.
Understanding Machinery Dynamics and Mechanism
We use cutting-edge fluorescence imaging to study how envelope protein complexes move and localise in real time. This lets us explore the spatial and temporal dynamics of these molecular machines, including energy-dependent rotation and other motion patterns critical for proper envelope assembly and function. Studying these dynamics provides insight into how bacteria coordinate complex molecular processes, which is key to understanding growth and survival.
Our core projects include:
Resolving Protein Complex Cooperativity
Using classical protein biochemistry and structural biology approaches such as single-particle cryo-EM, we investigate the Tol-Pal system and its interactions with the peptidoglycan synthesis machinery. These studies reveal how key protein complexes cooperate to stabilise the outer membrane and maintain peptidoglycan integrity. We can see how the systems compensate in knockout strains to preserve envelope function and bacterial survival. This work may uncover new targets for disrupting bacterial envelopes and combating antibiotic resistance.
Localisation of Cell Envelope Complexes in Cells
We are developing advanced cryo-electron tomography (cryo-ET) methods, incorporating DNA origami and bacteriophages, to capture bacterial cell envelope protein complexes in their native environment. By visualising these complexes at molecular resolution inside intact cells, we aim to understand how proteins assemble and interact to coordinate envelope construction. Resolving the spatial organisation of envelope machinery bridges the gap between cellular imaging and molecular detail, which is essential for elucidating molecular mechanisms.
Understanding Machinery Dynamics and Mechanism
We use cutting-edge fluorescence imaging to study how envelope protein complexes move and localise in real time. This lets us explore the spatial and temporal dynamics of these molecular machines, including energy-dependent rotation and other motion patterns critical for proper envelope assembly and function. Studying these dynamics provides insight into how bacteria coordinate complex molecular processes, which is key to understanding growth and survival.
Postdocs looking to pursue independent fellowships should contact Melissa to explore potential projects and support.