Role at ANSTO
Anton Le Brun is an instrument scientist on PLATYPUS, the time-of-flight neutron reflectometer at the OPAL research reactor. Prior to this he was a post-doctoral research fellow jointly between PLATYPUS and the National Deuteration Facility using neutron reflectometry to carry out nanoscale structural analysis of biomolecular systems.
Anton completed his BSc(Hons) in biochemistry at the University of York. After studying for an MRes in functional genomics also at the University of York, Anton went onto study for a PhD in biophysics in Professor Jeremy Lakey’s laboratory at the University of Newcastle upon Tyne. Before joining ANSTO, Anton worked for Diamond Light Source where he was involved in the commissioning of a beamline for high-throughput X-ray protein crystallography.
Membrane structural biology
Bacterial membranes are complex structures and simple yet, realistic models of the membrane are needed for the studying the binding of antibiotics, antibacterial peptides / toxins and nutrient transport. My focus in this work is to create models of the outer membrane of Gram-negative bacteria.
Recent success with this work includes deposition of a lipid bilayer on gold surfaces which also included the integral membrane protein, OmpF from E. coli. This system was completely characterised using novel form of neutron reflectometry by use of magnetic contrasts to enhance the quality of the data collected and to provide for more accurate modelling.
A second success has been to create model outer membrane surfaces at the air-liquid interface that incorporate lipopolysaccharides, the major component of the outer leaflet. This work included creating a deuterated form of the lipopolysaccharide and X-ray scattering studies to enhance and compliment the neutron reflectivity results.
This area of interest is in studying the structure of biomolecules that are immobilised to surfaces for use in devices or bioactive coatings. Understanding the structural assembly and arrangement of the surface-bound biomolecules provides information on the quality control in the assembly process as well helping to understand the surface activity of the devices.
Projects have involved the characterisation of membrane protein-based biosensors, self-assembled monolayers on titanium, assembly of tissue engineering scaffolds and characterisation of cubosome-based biosensors.
We now live in a world where bacteria that cause hospital acquired infections are becoming increasingly resistant to current antibiotic treatments. Antimicrobial peptides that attack the lipid component of the bacterial membranes are seen as new alternative to current antibiotics due to the improbability that bacterial can acquire resistant to the peptides.
The driving interest is to elucidate where in the membrane do these peptides bind and how does this affect the mechanistic action of the peptide and lead to the breakdown of the membrane and ultimately kill a bacterium cell.
This work has been in collaboration with a group from the University of Melbourne where the work has been on structurally characterising membrane-bound antimicrobial peptides from the skin secretions of Australian frogs. So far two very different peptides, one that has a pore-forming mechanism and the other a lytic mechanism, have been studied.