Lithgow Lab research
Biosketch: Professor Trevor Lithgow
Trevor Lithgow is an ARC Australian Laureate Fellow in the Biomedicine Discovery Institute at Monash University. Lithgow was awarded as one of the ten HFSP Outstanding Research Fellows, awarded the Roche Medal from the Australian Society for Biochemistry and Molecular Biology in 2004 and the David Syme Research Prize in 2005. In 2008 he was awarded the Beckman-Coulter Discovery Science Award of the Australian Society for Biochemistry and Molecular Biology and appointed as a Federation Fellow of the Australian Research Council. He received the Distinguished Alumni award by La Trobe University in 2009 and was elected Fellow of the Australian Academy of Sciences in 2010. In 2014 he was awarded an ARC Australian Laureate Fellowship. In 2016, Professor Lithgow was made an Honorary Professor at Wenzhou Medical University, China and he won the Royal Society of Victoria’s Medal for Excellence in Scientific Research in 2017.
Visit Professor Lithgow's Monash research profile to see a full listing of current projects.
We use a range of nanoscale methods to view and understand the bacterial cell surface. Work in our lab takes a fundamental approach to understanding the cell biology of bacteria. Using super-resolution microscopy and cryo-electron microscopy, we image nanoscale details of the bacterial cell surface: to open it up to drug treatment, to understand how bacteriophage attack and kill superbugs, and to find features that could be targets for bactericidal antibodies.
Much of our recent interest in bacterial cell biology has focused on how proteins are assembled into the outer membranes of bacteria: the molecular machinery in these processes is an excellent target for new drugs or phage-based therapies, and the surface-exposed nature of the machinery means that it could serve as a basis in new vaccine strategies. In recent years we mapped the evolution and topological features of the outer membrane protein assembly machinery, we solved the structure of key catalytic components, we discovered new components in this pathway and we are now very close to an understanding of the overall process of outer membrane assembly.
2. Understanding and reversing the evolution of antimicrobial resistance.
A major global issue is the rise of antibiotic-resistance (AMR) in bacterial pathogens or “super-bugs” that cause untreatable and oftentimes fatal infections in humans and in agricultural crops and animals. In addition, several sectors of industry in Australia are plagued by contamination with bacteria that are resistant to cleansing with antimicrobial treatments. From the plight of our waterways where bacterial (“blue-green algae”) contamination is devastating to water quality and the health of our native fish, to contamination of foodstuffs and thereafter food processing machinery in the food industry, to the deadly drug-resistant infections of increasing prevalence in our hospitals and other built environments. The evolution of AMR phenotypes has been moving unchecked for the past few decades. We have recently started working with collaborators in China, a front-line in the battle against drug-resistant bacterial infections.
While the evolution of AMR phenotypes in bacterial pathogens is a global problem, evolution is a reversible process. Finding the right combination of factors to reverse evolution is a clever means to turn the tide on AMR. One of the features of the evolutionary process that leads to AMR phenotypes is the remodelling of bacterial outer membranes: in Gram-negative bacteria, the permeability of the outer membrane dictates how well drugs get into the bacterial cell. We analyse outer membranes for changes in protein composition, we solve structures of outer membrane proteins, and compare genome sequence data to provide all of the information needed to understand the remodelling that has occurred, and what type of mutation drove the change.
3. Bacteriophage discovery and evolution.
Our lab surveys diverse environments to discover new bacteriophage that kill species and serovars of Klebsiella and Salmonella. To map and document their architecture, the phage are analysed by immunogold labelling and by single particle cryo-electron microscopy. We are discovering a range of new features in the tail machinery that the bacteriophage use to recognise and engage with the host bacterium. We chart the evolution of these new structural features via comparative genomics.
We are particularly interested in the commercial use of bacteriophage as control agents to decontaminate foodstuffs and food processing machinery, and as therapeutics to treat drug-resistant infections in humans as well as agricultural animals and crops. The selective pressure that bacteriophage place on superbugs has potential to reverse the evolutionary process leading to AMR phenotypes, re-sensitising bacteria to existing antibiotics.
We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).
Our research at the BDI is built on collaborations with A/Professor Fasseli Coulibaly, Dr Jeremy Barr, Dr Mike McDonald, Dr. Sheena McGowan, Professor Jian Li, A/Professor Vijaykrishna Dhanasekaran and A/Professor Jiangning Song. We also work nationally and internationally with:
Professor Gordon Dougan - University of Cambridge, UK
Professor Richard Strugnell - The University of Melbourne, Australia
Professor Tieli Zhou - Wenzhou Medical University 1st Affiliated Hospital, China
Dr Matthew Belousoff - Monash Institute of Pharmaceutical Sciences, Australia
Professor Tracy Palmer - Newcastle University, UK
Dr Iain Hay - University of Auckland, New Zealand
Professor JC Gumbart - Georgia Tech, USA
Professor Zi-Bing Jin - Wenzhou Medical University, China
Professor Robert T. Schooley, M.D. - University of California San Diego, USA
Professor Ilari Maasilta - University of Jyväskylä, Finland
Dr Takuya Shiota - Miyazaki University, Japan
Dr Theron Hamilton - LCDR, MSC, US Navy Jacksonville, USA
Professor Diego Ramírez-Lovering - RISE Water Security Team, Indonesia
Professor Gabriel Waksman - Birbeck College, UK
A/Professor Shu Sin Chng - National University of Singapore, Singapore
Professor Susan Buchanan - NIH-NIDDK Bethesda, USA
Professor Sam Kariuki - Centre for Microbiology Research in Nairobi, Kenya
Professor Sheena Radford - Leeds University, UK
Professor Toshiya Endo - Kyoto University, Japan
Current research opportunities
The Lithgow Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.
Projects in this lab are formulated based on student aspirations and expectations. Please send a short project proposal to firstname.lastname@example.org explaining your desire for research training. If your ambition can be accommodated, we will discuss this with you.
Scholarship support is available to new PhD students. PhD postgraduate scholarships are available for Australian citizens or permanent residents with a H1 Honours degree. We have positions for international students: applicants are advised to check the Graduate studies web pages for information on entry requirements, tuition fee, and scholarships prior to application.
Postdocs opportunities are also available and you are encouraged to contact Professor Trevor Lithgow regarding potential projects that align with the presented research themes.