Dr Xiao Yang
ARC Research Fellow
School of Environmental and Life Sciences
It's in the genes
Spanning all levels of biological organisation, Dr Xiao Yang's research into intricate antibiotic-disease relationships is helping to combat the spread of multi-drug resistant bacteria.
Most of us don't give much thought to how the human body works - it just does. The tiny, molecular processes that allow us to breathe and move and sleep are almost impossible to imagine, operating on a scale far below normal perception. For Yang though, they are neither out of sight nor out of mind.
'My research focuses on the structure and function of the bacterial transcription,' she explains.
'This activity is long and complex.'
Yang is combining elements of molecular biology, structural biology and biochemistry in her studies, gaining in-depth information about regulation of gene expression in bacterial cells.
'I specifically look at essential protein-protein interactions between an enzyme called RNA polymerase and other factors,' she clarifies.
'These interactions are involved in bacterial transcription, which is the process by which RNA polymerase synthesises RNA from its template DNA.'
'A number of accessory proteins, or transcription factors, are involved as well.'
The early career academic is using this knowledge in several ways, principally investing her efforts in the design and testing of inhibitors that act against pathogenic bacteria. Echoing concerns from the World Health Organisation about the dramatic rise of antibiotic resistant diseases, she's also in the middle of creating a new generation of antimicrobial compounds.
'It's a serious public health problem,' Yang asserts.
'But the more we understand about these interactions, the better equipped we'll be to target them.'
Serendipity and success
Yang's groundbreaking research career began in the late 2000s when she undertook a PhD in molecular biology. Looking specifically at a transcription factor called N utilisation factor A during the four-year probe, the bilinguist sought to explore the structure of essential protein-protein interactions. Discovering a new subunit of bacterial RNA polymerase by chance was an added – and prolific – bonus.
'People used to think RNA polymerase only had five subunits: two alpha, beta, beta prime and omega,' she concedes.
'But when I purified it from Bacillus subtilis, I noticed the latter was a little bigger than usual.'
'I followed this up with mass spectrometry, chromatography and a literature review and found the smaller and bigger omegas to be two distinct subunits.'
The first scientific breakthrough of its kind in 45 years, this new subunit gene was impressively named after Yang. The discoverer's chance encounter with rpoY also provided an opportunity for the University of Newcastle to experiment with single particle analysis based on electron microscope images. Now a recognised leader in the field, Yang used the method to resolve the new subunit's structure and binding site on RNA polymerase.
'This involved using thousands of images of microscopic particles to derive the overall shape of a large protein complex,' she affirms.
'It can result in structural data from proteins that are not amenable to other structural studies.'
Small things with big impact
Yang has continued investigating RNA polymerase post-PhD, initiating a raft of innovative biochemical research projects on essential transcription factors.
'To make RNA from its template DNA, RNA polymerase needs to appropriately express certain genes according to specific conditions,' she discloses.
'They are necessary for bacterial growth.'
'Without them, the cell will die.'
Yang is also currently exploring the opportunities presented by a firmer understanding of the interaction. Chiefly experimenting with drug design and testing in this area, the molecular biologist's work has attracted considerable interest from renowned scholars around the world.
'Inhibitors have the potential to serve as the leads for novel antibiotic development,' she reveals.
'These developments can then lead molecules to target bacterial transcription.'
In an unusual twist, Yang is simultaneously in the process of developing inhibitors against novel bacterial targets. Signing on to the joint venture with Chinese chemists' midway through 2013, the structural expert is using target deconvolution strategies in these latest drug discoveries.
'We've located a group of compounds that show excellent antibiotic activity, especially when compared to the ones available commercially,' she says.
'They were derived from traditional Chinese medicine.'
With the bacterial target for the antimicrobial compounds still unclear, Yang's team is set to continue investigating in 2015.
'Having recently identified the target, we will be able to determine how the compounds kill bacteria,' the 2014 faculty winner of the Vice Chancellor's Award for Research Excellence declares.
'This will then allow them to be modified and improved.'
'We're hoping to prevent the spread of multi-drug resistant bacteria.'
December 9, 2014
Each year the University of Newcastle celebrates the remarkable achievements of our staff at the Vice-Chancellor's Awards ceremony.