2023 Projects Microbiology-Hons-Booklet

Department of Microbiology
2023 Honours Programs

in Microbiology
2023 Honours Coordinator Deputy Coordinator
Professor John Boyce Professor Chris Greening
Room: 215, 19 Innovation Walk Room: 136, 19 Innovation Walk
Phone: +61 3 9902 9179 Phone: +61 3 9905 1692
Email: john.boyce@monash.edu Email: Chris.Greening@monash.edu
monash.edu/discovery-institute
2023 Honours Programs in Microbiology
The Honours programs for both Bachelor of Biomedical Supervisor Interviews

Science (BBiomedSci) and Bachelor of Science (BSc)
contain coursework and an independent research project. Applicants are encouraged to discuss research projects with
The objectives of these courses are to develop the laboratory potential supervisors at any suitable time, by appointment.
skills required for research in microbiology and the ability Following these discussions, students should apply online
to critically evaluate microbiological research. Students at the relevant faculty site and give Professor John Boyce
also achieve a detailed understanding of specialised topics a copy of their application forms: www.monash.edu/discovery-
in microbiology and enhance their communication skills in institute/honours/so-how-do-i-apply indicating their project
written and oral presentations. preferences, and any additional documentation required. You
do not need to wait until November 11th to hand in your
The Department looks forward to welcoming you in 2023. preference forms, the earlier the better.
We feel that our friendly, constructive and highly productive
working environment provides an excellent opportunity for
honours students to develop an understanding of the research Projects Outside the Department
process and to achieve their full research potential. It is possible for students to complete their coursework within
the Department of Microbiology at Clayton, and their research
Formal Application Process project off-campus. Under these circumstances, students
must travel between locations when required. The thesis
Application for Microbiology Honours entry involves examination takes place at the same time for all students
a two part application process. enrolled through Microbiology.
1. Formal application to the relevant faculty by
B. Sc (Hons): November 11, 2022 Microbiology Coursework

www.monash.edu/discovery-institute/honours/so-how-do-i-apply The coursework conducted within the Department of
B. Biomed. Sci (Hons): November 11, 2022 Microbiology consists of short courses termed colloquia,
www.monash.edu/discovery-institute/honours/so-how-do-i-apply a statistics course and a seminar series. BSc students need
to complete two colloquia, BBiomedSci students complete
2. Submission of project preferences to Professor John one colloquium. Each colloquium is held during a one month
Boyce (no later than November 10, 2022). period in the first half of the year, so that the coursework is
usually completed, and students receive some feedback on
Research Projects their progress, by mid-year. The format of the colloquia will
vary. Most involve reading recent research papers, an oral
The research project is the major component of both programs.
or poster presentation, and a written assignment.
All efforts are made to accommodate students in the laboratory
of their choice, and to develop research projects that take into
account the student’s, as well as the supervisor’s, interests. BBiomedSci Common Core Coursework
Brief outlines of the available projects for 2023 are in the In addition to one colloquium, all BBiomedSci Honours
following section. students must complete a centrally assessed common
coursework component consisting of:
i A statistics module, with accompanying MCQ test and

written take home assignment
i A written critique of a scientiﬁc paper, in a three-hour

examination format
2023 Microbiology Honours Projects | 1

Literature survey Eligibility
During first semester the students must submit a literature Monash BSc Students
survey on their research project. The literature survey (which
Entry to the course is restricted to those students who have
can be used as the basis for the introduction in the final
qualified for the award of the pass degree of BSc (all subjects
report) allows the identification early in the year of those
completed before enrolment), and have an average of at
students who have problems with English expression so this
least 70% in 24 points of relevant level-three science units.
can be addressed by directed English writing instruction. It
This generally includes at least 18 points of Microbiology
also, of course, compels the students to become thoroughly
units. Students studying combined Science degrees must be
conversant with their area of research.
eligible for the award of BSc.
Additional requirements BSc Graduates of Other Universities

As for Monash students, applicants are required to have a
The programs will commence on February 20, 2023
BSc and distinction grades in Microbiology or closely related
(mid year begins July 17) with a series of introductory
subjects. A certified copy of the applicant’s academic
lectures, before the students start work on their research
record and a statement to the effect that they have
projects. These lectures contain information on the course,
qualified for a pass degree are required as soon as they
departmental facilities and laboratory safety. In the second
are available.
half of the year students may be given specific training in
the presentation of written reports, and in oral presentation Monash BBiomedSci students
of their work. It is compulsory for students to attend the
Students must have completed all requirements for the
introductory lecture course, all departmental seminars, and
award of the pass degree of Bachelor of Biomedical Science
any short courses on written and oral presentations.
offered at Monash University. They must also have an
average of 70% or higher in at least 24 points at third year
Assessment level, with 12 points from third year core units.
Final assessment of the BSc Honours program BBiomedSci graduates from other universities
follows the format:
Students applying for admission based on a qualification
Literature survey 7.5% other than the pass degree of Bachelor of Biomedical
Science offered at Monash University will need to
Research report/report review 60% demonstrate that they have achieved an appropriate
Seminar 7.5% standard in studies comparable to 24 points of BBiomedSci
subjects as stipulated above.
Microbiology coursework 25%
Part-time study and mid-year entry

Final assessment of the BBiomedSci Honours program
The department prefers students to study on a full-
follows the format:
time basis. However, it may be possible under special
Literature survey 7.5% circumstances to complete the Honours degree in two
consecutive years by doing the coursework and research
Research report/report review 60% project in separate years. It is also possible to start the
course mid-year. In both of these circumstances, the
Seminar 7.5%
arrangements are made on an individual basis between
Microbiology coursework 10% applicants and supervisors.
Statistics Module 7.5%
Common written component 7.5%
2 | 2023 Microbiology Honours Projects

Research Projects
2023

Professor John Boyce
EMAIL john.boyce@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9902 9179
OFFICE Room 215, 19 Innovation Walk (Building 76)
WEB https://www.monash.edu/discovery-institute/boyce-lab
Professor John Boyce Dr Marina Harper Scanning electron microscope image of Pasteurella multocida
Characterising the role of small RNAs in Defining the Mechanisms of Pasteurella

Acinetobacter baumannii virulence multocida Pathogenesis and improving
Professor John Boyce, Ms Amy Wright and vaccines
Professor Anton Peleg Dr. Marina Harper, Dr. Thomas Smallman
Acinetobacter baumannii has been identified as one of the and Professor John Boyce
top three dangerous Gram-negative hospital pathogens as Pasteurella multocida is a Gram-negative bacterial pathogen
it can cause a range of life-threatening infections and most that causes a range of diseases in humans, cattle, pigs
strains are now resistant to the majority of current antibiotics. and poultry. The animal diseases result in serious economic
Small RNA molecules (sRNAs) are important regulators losses worldwide in food production industries. We are
of bacterial gene expression and play an important role interested in understanding the molecular mechanisms of
in A. baumannii virulence and antibiotic resistance. sRNA pathogenesis in this bacterium with an aim to developing
regulatory networks form a possible target for future new, more effective and widely applicable vaccines or
therapeutic interventions aimed at killing or reducing the antimicrobial drugs.
virulence of multidrug resistant A. baumannii strains. We are Recent work in our lab, using comparative genomics and
interested in defining new sRNAs that control important A. transposon insertion site mutagenesis, has comprehensively
baumannii phenotypes. defined the P. multocida genes essential for a range of
In this project you will use cutting-edge molecular biology, virulence phenotypes, including growth in serum and
mutagenesis, high-throughput -omics, and sRNA-mRNA production of the anti-phagocytic bacterial capsule. With
and sRNA-protein interaction analyses to identify novel this crucial data as a base, in this project we will use
sRNAs and define their targets. These experiments will be directed mutagenesis, complementation, whole-genome
complemented by a range of phenotypic assays including transcriptomic and proteomic techniques and established in
biofilm formation, antibiotic resistance and growth on vitro and in vivo assays to define the molecular mechanisms
different substrates to determine the precise roles of by which this important pathogen avoids killing by the host
particular sRNAs in A. baumannii biology. These studies will immune system and causes disease. Furthermore, we will
lead to the identification of targets for future intervention test selected mutants as live-attenuated vaccine candidates
strategies aimed at reducing the health burden of nosocomial in our chicken disease model.
infections.

Professor Mariapia Degli-Esposti
EMAIL mariapia.degli-esposti@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9905 6162
WEB https://research.monash.edu/en/persons/mariapia-degli-esposti
Professor Mariapia Degli-Esposti Dr Iona Schuster Dr Christopher Andoniou
MCMV, Immunity and Ageing Viral Infection and Autoimmunity

Professor Mariapia Degli-Esposti, Professor Mariapia Degli-Esposti
Dr Christopher Andoniou and Dr Iona Schuster and Dr Iona Schuster
With average life spans increasing we face novel challenges Viral infections have long been suspected to play a role in
in managing age-associated health decline. A key factor autoimmunity, with members of the herpes virus family such
in maintaining overall health is a well-functioning immune as cytomegalovirus (CMV) specifically implicated. We use the
system. However, as we age the immune system becomes model of murine CMV, a natural pathogen of the mouse with high
less functional with reduced production of T and B cells, as similarity to its human counterpart, to investigate the mechanisms
well as changes in the quality and composition of respective underlying the generation of protective antiviral responses and
memory subsets. How immunological challenges such as how these correlate with the onset of autoreactive responses. We
viral infections impact and shape the aging immune system have shown that a strong anti-viral T cell response generated in
is not well understood. In this regard, we are particularly the absence of certain immune regulatory mechanisms improves
interested in cytomegalovirus (CMV), a virus that is never fully viral control. However, once the virus is controlled, this strong
cleared and remains with its host life-long. CMV infection anti-viral response leads to increased generation of auto-specific
causes the gradual expansion of certain CD8+ T cell memory immune responses resulting in a loss of tissue function. The
populations, a phenomenon that has been linked with autoimmune disease generated represents the best available
both limiting and enhancing immune responses to other model of the second most common autoimmune disease of
challenges. Using the well-established mouse model of man, Sjogren’s Syndrome, a condition that affects overall health
murine CMV (MCMV) infection we aim to examine the impact by severely compromising exocrine gland function. Experimental
of this in immune compartments during ageing. Approaches approaches will include in vitro and in vivo techniques using
will include high-parameter multicolour flow cytometric wildtype as well as gene-targeted mouse strains. Techniques
analysis of immune cell subsets as well as bulk and single include the preparation of different tissues for histological analysis
cell assays of immune functionality. The ultimate aim is to of tissue pathology, characterization of infiltrating cell types, and
gain a better understanding of how CMV infection shapes assessment of changes in tissue architecture. Furthermore,
the immune system over time and how this affects the aging we use flow cytometry to characterize and quantify immune
immune system. cell populations isolated from different tissues at various times
post infection. The goal of this project is to further extend our
understanding of the processes and mechanisms underlying the
generation of autoreactive immune populations in the context of
viral infection.

Professor Chris Greening
EMAIL chris.greening@monash.edu
THREE VACANCIES
TELEPHONE +61 3 990 51692
WEB http://www.greeninglab.com
Professor Chris Greening Dr Rachael Lappan Dr Tom Watts
Carbon monoxide: poison or fuel for Gas metabolism: a new frontier in the
Mycobacterium tuberculosis? human microbiome revolution
Professor Chris Greening, Dr Tom Watts and Dr Professor Chris Greening, Caitlin Welsh and Dr
Thomas Naderer Samuel Forster
Tuberculosis infects one third of the world’s population Within the human gastrointestinal tract, our microbiota
and was the single biggest killer from infectious disease constantly perform a range of metabolic processes that
worldwide in 2019. Its causative agent, Mycobacterium influence our health. The recent ‘microbiome revolution’ has
tuberculosis, resides in patient’s lung for decades in a revealed a range of metabolic by-products that have links
latent state that evades immune defences and resists with gut dysregulation and disease. Yet the mediators of gas
drug treatment. Our laboratory is investigating the metabolism, an important process performed by these gut
mechanisms that allow this pathogen to stay energised microbes, are still largely unresolved. Bacterial fermentation
during such infections. One overlooked energy source for within the human gut produces hydrogen gas (H2), and other
this pathogen is carbon monoxide gas. During infection, groups of microbes (such as sulfate, nitrate and fumarate
macrophages produce this gas in large quantities through reducers) are responsible for its subsequent disposal. A
heme oxygenase-1 as a probable defence strategy. delicate balance of these processes must be achieved to
Moreover, the pathogen can be exposed to large amounts prevent accumulation of H2 and other potentially harmful
of carbon monoxide through cigarette smoking and air related metabolic by-products, which have been linked to
pollution. Alarmingly, we have uncovered evidence that colorectal cancer, IBS and IBD. Furthermore, exploring these
mycobacteria not only tolerate this gas, but in fact use it as processes in the gut microbiota can aid in our understanding
an energy source through the enzyme carbon monoxide of how opportunistic gut pathogens, such as Clostridium
dehydrogenase. In this project, you will investigate PC2 perfringens and Clostridioides difficile, can utilise them
strains of Mycobacterium tuberculosis in both pure culture in infection. In this study, you will use culture-dependent
and macrophage infection models. You will derermine, methods to investigate how these H2-related metabolic
through CRISPR interference, if carbon monoxide oxidation processes occur within the human gut, who the key bacterial
is mediated by carbon monoxide dehydrogenase, and test players are, and how these processes affect overall human
whether this enzyme and carbon monoxide supplementation gut health and disease. Depending on your interests,
enhances long-term survival. This project has potential projects can either focus on beneficial bacteria, opportunistic
to reshape our view of how the world’s most successful pathogens, or potential carcinogens.
pathogen lives: revealing how a host-derived inorganic
defence molecule is exploited as an energy source.

Novel survival strategies of archaea in Antimicrobial resistance in Antarctica and
extreme environments other pristine ecosystems
Professor Chris Greening, Pok Man Leung Professor Chris Greening, Dr Rachael Lappan
Discovered less than 50 years ago, archaea are the The resistance of human pathogens to antibiotics is an
enigmatic third domain of life and our ancient ancestors. increasingly important issue for human health, with many
Diverse archaea reside in all ecosystems, spanning antimicrobial resistance genes readily passed between
soils, waters, and our guts, and they dominate extreme bacteria via plasmids and resistance selected for by the
environments such as hot springs and salt lakes. Yet little use (or overuse) of antimicrobials. However, antimicrobial
is known about how they survive limitation or variations resistance is not restricted to pathogens; it is likely an
in nutrient availability that occur in these environments. ancient strategy for microbial survival, enabling bacteria to
We have made the unprecedented discovery that most compete and survive in a range of environments. Little is
aerobic bacteria can ‘live on air’; more precisely, they known about the prevalence and nature of antimicrobial
survive starvation for their preferred energy sources by resistance in ecosystems that are not dominated by humans,
scavenging two atmospheric trace gases, hydrogen and including Antarctica, other deserts, and cave systems. This
carbon monoxide. Aerobic archaea also encode the genes project aims to evaluate the antimicrobial resistance profile
for trace gas consumption, though no study has yet (the resistome) and the array of plasmids (plasmidome) in
tested whether they can live on air. In this study, you will such environments to understand how bacteria disseminate
grow thermophilic archaea isolated from volcanic springs antimicrobial resistance, compete and survive. The project
(Sulfolobus spp.) and salt lakes (Haloplanus spp.). You will primarily involves the use of metagenomic data and
use cutting-edge systems biology approaches (proteomics bioinformatic analysis, so a student with some computational
and transcriptomics) to gain a systematic understanding of experience (e.g. through bioinformatics units) would be
how these organisms survive starvation. In addition, you will well suited to this project. There is also the opportunity
perform activity measurements to determine whether they for culture-based work and susceptibility testing on novel
can consume atmospheric hydrogen and carbon monoxide bacterial isolates from these environments, with the project
during growth and survival. This project is ideally suited tailorable to the student’s interest in developing skills in both
for a BSc student keen to work on something exciting yet laboratory and computational areas.
different.

Dr Rhys Grinter
EMAIL rhys.grinter@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9905 8924
Dr Rhys Grinter The structure of the outer-membrane transporter FusA and its substrate complex
The crystal structure of the outer-membrane protein BonA
Lab Biography
The Grinter lab studies how bacterial pathogens shape The lab is multidisciplinary, utilising a combination of cellular
their physiology on a molecular level to infect their hosts, microbiology, genomics, biochemistry, and structural
and how these adaptions can be targeted to develop novel biology to provide multifaceted insights into the above
antimicrobial therapies. Of key interest to the lab are how processes. These discoveries form the basis for developing
Gram-negative bacterial pathogens (including Neisseria these targets for antimicrobial intervention.
gonorrhoeae and Haemophilus influenzae) obtain the
The lab is looking for up to two honours student to recruit to
essential nutrient iron from their host, by using specialised
one of the projects outlined below.
transporters that steal it directly from host proteins. We are
also interested in how bacteria of the genus Mycobacterium
have adapted to survive in harsh environments and the
host to become some of the most successful pathogens
of humans.

Project 1: Understanding and isolating Project 2: Understanding the PE/PPE
heme transporters from the outer proteins present in the outer envelope of
membrane of Haemophilus influenzae Mycobacterium tuberculosis.
Haemophilus influenzae is a Gram-negative bacterium that Bacteria of the genus Mycobacterium possess an outer
is an obligate inhabitant of the human respiratory tract. Most membrane in addition to their inner cytoplasmic membrane.
commonly it lives in our throats as a harmless commensal; This membrane has a unique structure and is composed
however, it can cause serious disease. Before the of exotic lipids, not found in other organisms. This outer
introduction of the H. influenzae type b (Hib) vaccine in the membrane is an effective diffusion barrier, protecting
1980s H. influenzae infection was a serious cause of death the mycobacterial cells from a hostile environment or
due to meningitis and pneumonia, particularly in children attack by the host immune system. This is especially
under five. The Hib vaccine greatly reduced these deaths; true for Mycobacterium tuberculosis, the causal agent
however, H. influenzae strains that escape this vaccine of tuberculosis. The outer membrane of M. tuberculosis
and are resistant to antibiotics have emerged. These non- contains high concentrations of lipids not found in non-
typeable H. influenzae (NTHi) are a major cause of ear and pathogenic mycobacteria and is even more impermeable
throat infections in children, and infection rates are rising. than other species. While there is still much we don’t
understand about the function of this membrane, it likely
One of the most important nutrients for H. influenzae
plays a key role in the pathogenesis of M. tuberculosis. To
during infection is the iron-containing cofactor heme. H.
functionalise its outer membrane M. tuberculosis produces
influenzae cannot synthesize heme and so obtains it from
and embeds a large number of proteins in this structure. The
host haemoglobin using specialised transporters in its
PE/PPE proteins are one such family of outer membrane
outer membrane. In the project, we will seek to understand
proteins found predominantly in pathogenic mycobacteria.
how the expression of these haemoglobin transporters
They appear to possess a conserved delivery module that
is regulated in response to an abundance or scarcity of
targets them to the outer membrane as well as diverse
heme. To achieve this, we will utilise biochemistry to isolate
functional domains. These functional domains are important
outer membranes from H. influenzae grown with different
for virulence, nutrient transport, and adhesion to host
concentrations of heme. We will then utilise SDS-PAGE
cells. However, very little is known about the structure
and mass spectrometry to determine how the abundance
of these proteins or how they function. This project will
of outer membrane haemoglobin transporters changes in
utilize bioinformatic tools and protein structure prediction,
response to heme concentrations. Next, we will use this
to classify and characterize the PE/PPE proteins from M.
knowledge to isolate and purify haemoglobin transporters
tuberculosis, to determine their likely function and potential
from H. influenzae membranes and use structural biology
roles in virulence. This work will be utilized to identify targets
and biochemistry to determine how they bind haemoglobin
for genetic, biochemical, and structural characterization in
and transport heme.
the lab.
Because H. influenzae requires exogenous heme to grow, we
PE/PPE proteins are known to be important for the virulence
can block its access to this nutrient as a means of preventing
of M. tuberculosis; however, very little is known about
or treating infection. The understanding of haemoglobin
what their function is or how they mediate it. This project
transporters provided by this project will assist in the design
will work to answer these important questions, identifying
of inhibitors that block heme-uptake.
novel virulence factors that can be targeted for antimicrobial
intervention.

10 | 2023 Microbiology
MicrobiologyHonours
HonoursProjects
Projects
Dr Terry Kwok-Schuelein
EMAIL terry.kwok@med.monash.edu.au
TWO VACANCIES
TELEPHONE +61 3 9902 9216
OFFICE Room 231, level 2, 19 Innovation Walk (Building 76)
Dr Terry Kwok-Schuelein The oncogenic type IV secretion system (T4SS) of H. pylori (left) is activated upon
H. pylori-host interaction (right).
The Molecular Mechanisms by Which Our team uses multi-disciplinary state-of-the-art approaches
to study the molecular mechanism of H. pylori type IV
Helicobacter pylori Causes Stomach Cancer secretion and H. pylori-host interactions. We aim to
Helicobacter pylori is a Gram-negative gastric bacterium that understand the molecular basis of how H. pylori induces
has co-evolved with humans for more than 50,000 years. It stomach cancer, with the ultimate goal of providing
colonises the stomach of over 50% of the world’s population, knowledge for a better treatment and/or prevention of H.
making it one of the most prevalent human pathogens. It is a pylori-associated stomach diseases. Projects are available to
causative agent of severe gastric diseases including chronic address the following key questions:
gastritis, peptic ulcer and stomach cancer. H. pylori has been i How does H. pylori trigger inflammation and
classified as a Group I (high-risk) carcinogen. carcinogenesis through the virulence functions of CagL
Highly virulent strains of H. pylori harbour a type IV secretion and CagA?
system (T4SS), a secretion machinery that functions as a i Can cagL and cagA genotypes predict gastric cancer risk
“syringe” for injecting virulence proteins and peptidoglycan and therefore help pinpoint cancer-prone patients for early
into the host cell. We discovered that CagL, a specialised treatment?
adhesin present on the surface of the H. pylori T4SS, binds i How does CagL function as a host-activated sensor
to the human integrin α5β1 receptor on stomach lining cells. during type IV secretion?
This binding activates the T4SS and hence the secretion
i How do CagL and CagA modulate host cell signalling
of virulence factors including the highly immunogenic and
during chronic H. pylori infection?
oncogenic protein, CagA, into stomach cells. ‘Injected’ CagA
i Can we utilise the type IV secretion system of H. pylori
then interacts with host signalling molecules and triggers
for delivery of therapeutic proteins?
activation of a suite of host responses. Interestingly, our
recent findings suggest that CagL can also directly modulate The available honours projects will enable one to gain
host cell functions. The precise mechanisms by which CagL experience with the important techniques of molecular
functions both as a host-activated sensor of the H. pylori cloning and mutagenesis, bacterial culture, eukaryotic cell
T4SS and as a direct activator of aberrant host responses culture techniques, mouse infection models, CRISPR, RNAi,
remain to be fully understood. immunostaining, Western blotting, ELISA, confocal laser
scanning microscopy, live cell imaging, etc. Someone who is
enthusiastic in learning about the exciting secrets of bacteria-
host interactions, infectious cancer biology and bacterial
pathogenesis is strongly encouraged to apply.

Professor Jian Li
EMAIL jian.li@monash.edu
THREE VACANCIES
TELEPHONE +61 3 9903 9702
WEB https://research.monash.edu/en/persons/jian-li
Professor Jian Li Dr Sue C. Nang Dr Yan Zhu Dr Jinxin Zhao
Laboratory of Antimicrobial Systems Deciphering the Mechanisms of

Pharmacology Antimicrobial Resistance and Phage
My lab focuses on antimicrobial discovery and pharmacology Infection in Gram-negative bacteria Using
against Gram-negative ‘superbugs’ (namely Pseudomonas Computational Biology
aeruginosa, Acinetobacter baumannii, and Klebsiella
Dr Yan Zhu, Dr Jinxin Zhao and Professor Jian Li
pneumoniae). There has been a marked decrease in the
discovery of novel antibiotics over the last two decades. Antimicrobial resistance is a critical threat to human health
As no novel class of antibiotics will be available against worldwide. Polymyxins are a group of last-line antibiotics
Gram-negative ‘superbugs’ in the near future, it is crucial to against Gram-negative ‘superbugs’, including MDR.
optimise the clinical use of ‘old’ polymyxins using systems Acinetobacter baumannii, Klebsiella pneumoniae and
pharmacology and to develop new-generation antimicrobial Pseudomonas aeruginosa.
lipopeptides and innovative therapeutics. We are integrating genomics, transcriptomics, proteomics,
My major research programs include: metabolomics, and lipidomics to systematically examine
bacterial responses to antimicrobial treatment and phage
(1) optimising clinical use of antimicrobial and phage
infection.
therapies using pharmacokinetics/pharmacodynamics/
toxicodynamics (PK/PD/TD) and systems pharmacology; This project aims to:
(2) elucidation of mechanisms of antibacterial activity, 1. conduct comparative genomic analysis for phages to
resistance, and toxicity of antimicrobials and phages; and predict critical genetic determinants of infection;
2. construct genome-scale models for A. baumannii,
(3) discovery of new-generation antimicrobial lipopeptides
K. pneumoniae and P. aeruginosa using multi-omics
and innovative therapeutics against multidrug-resistant
data;
(MDR) Gram-negative bacteria.
3. employ the constructed genome-scale models to
My lab is funded by the US National Institutes of Health (NIH)
simulate bacterial responses to antimicrobials and
and Australian NHMRC.
phage infections;
4. predict key genes and pathways contributing to
bacterial resistance to antibiotics and phages and
validate their functions with our comprehensive mutant
libraries.

This multidisciplinary project will characterise the complex regimens also depend on the dynamics of infection and
interplay of signaling, regulation and metabolic pathways host responses, innovative strategies incorporating systems
involved in resistance to antimicrobal killing and phage pharmacology and host-pathogen-phage-antibiotic
infection, thereby optimising antimicrobial combination and interactions have a significant potential in optimising phage-
bacteriophage therapies in patients. antibiotic combinations. This project will employ cutting-
edge systems pharmacology to generate urgently needed
Phage-Antibiotic Therapy information for rationally optimising novel phage-antibiotic
combinations in patients.
in the Postantibiotic Era
Dr Sue C. Nang and Professor Jian Li
Pulmonary Toxicity of Novel Polymyxin
Antimicrobial resistance has become one of the greatest Combination Therapies
global threats to human health and pandrug-resistant
Professor Jian Li
(PDR) K. pneumoniae has been identified by the WHO as
one of the 3 top-priority pathogens urgently requiring novel Current dosing recommendations of parenteral polymyxins
therapeutics. These ‘superbugs’ cause life-threatening are suboptimal for treatment of respiratory tract infections
infections, particularly in the critically ill, and polymyxins due to poor drug exposure at the infection site. Moreover,
are often used as the last option. Worryingly, increasing nephrotoxicity is the dose-limiting factor and can occur in
emergence of polymyxin resistance highlights the urgency up to 60% of patients. Pulmonary delivery of polymyxins
to develop novel therapeutics to treat PDR K. pneumoniae. as monotherapy and in combination with other antibiotics
Bacteriophage (i.e. phage) have recently attracted substantial has offered a great promise for bacterial eradication in the
attention as a potential alternative against PDR bacterial respiratory tract. However, we have shown that polymyxins
infections; however, resistance to phage therapy (including localise in mitochondria of human lung epithelial cells and
cocktails) in K. pneumoniae can rapidly develop. Fortunately, activate multiple apoptotic pathways. This multi-disciplinary
phage resistance may restore bacterial susceptibility to project aims to investigate the effect of polymyxins and
certain antibiotics and therefore, optimal phage-antibiotic their synergistic combinations with other key classes of
combination therapy provides a superior approach to fight antibiotics on human lung epithelial cells, using fluorescence
against these superbugs. Contemporary antimicrobial activated cell sorting (FACS), metabolomics, proteomics,
pharmacology plays a critical role in optimizing antibiotic transcriptomics and cutting-edge imaging techniques. This
dosage regimens, but lacks systems and mechanistic project will provide the much-needed pharmacological
information. Importantly, antibiotic dosing strategies cannot information for safer and more efficacious use of polymyxin
be easily extrapolated into phage therapy, mainly due to the inhalation therapy against life-threatening lung infections.
complex disposition, host specificity and self-replication of
phages.
As the optimal phage-antibiotic combination and dosage

Professor Trevor Lithgow
EMAIL trevor.lithgow@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9902 9217
OFFICE Room 233; Room 252, 19 Innovation Walk
WEB https://www.monash.edu/discovery-institute/lithgow-lab/home

Lithgow lab group
Bacterial Cell Biology Laboratory bioinformatics to predict effector proteins for type 6 secretion
system with high accuracy (Wang et al. 2018. Bioinformatics
Bacterial cells were once dismissed as ‘bags of enzymes’ 34:2546), and Chris Stubenrauch’s paper on the mechanism
with minimal organization. Yet in the past 10 years it behind how E. coli assembly fimbriae in urinary tract
has become clear that bacteria segregate many cellular infections (Stubenrauch et al. 2016. Nature Microbiol
processes into subcellular structures (Greening & Lithgow 1:16064).
Nature Reviews Microbiology 18:677). The Bacterial
Cell Biology Lab uses all the tools of molecular cell biology
to study and image bacteria at the sub-cellular level, and From a recent global assessment published in The
Honours, Masters and PhD students in this lab are trained Lancet, we now know that human deaths associated with
how to manage their project work towards at least one first- antimicrobial resistant (AMR) bacterial infections are much
author paper in a major journal. This is a critical outcome to worse than we had feared. In 2019, 5 million people died
ensure that graduates from the lab are offered exciting jobs with infections due to AMR bacteria making AMR the third
(https://www.monash.edu/discovery-institute/lithgow-lab/ biggest global killer of people, just behind ischemic heart
members). disease and stroke. Across the world, six bacterial species
contribute most to the burden of AMR deaths: E. coli,
Staphylococcus aureus, K. pneumoniae, Streptococcus
Examples of our recent PhD student publications include pneumoniae, Acinetobacter baumannii and Pseudomonas
Eric Mandela’s paper on spatial control that bacteria exert aeruginosa. In the Bacterial Cell Biology Lab, we have
on their cell walls (Mandela et al. 2022. eLife 11:e73516); focussed our studies on three of these species: E. coli,
Manasa Bharathwaj’s paper on how carbapenemases are S. aureus and K. pneumoniae, with many of the current
secreted by Klebsiella pneumoniae (Bharathwaj et al. 2021. projects addressing the mechanisms of AMR in E. coli and K.
mBio12:e0130221), Von Torres’ paper on how hypervirulent pneumoniae, and the search for new phages as therapies for
K. pneumoniae assemble their outer membranes (Torres et infections caused by S. aureus and K. pneumoniae.
al. 2018. Mol Microbiol 109:584), Dilshan Gunasinghe’s
paper on the systems-level control of outer membrane
protein assembly in Escherichia coli (Gunasinghe et al. 2018.
Cell Reports 23:2782), Jiawei Wang’s paper on using

Predicting the evolution of AMR The search for new phages as therapies
in Escherichia coli and Klebsiella for infections caused by Staphylococcus
pneumoniae. aureus (MRSA) and Klebsiella
Dr. Chris Stubenrauch and Professor Trevor Lithgow pneumoniae
Efflux pumps are membrane-spanning channels that use
Dr. Rhys Dunstan and Professor Trevor Lithgow
ATP hydrolysis to power the efflux of a range of molecules
out of bacterial cells. Within this one readily defined group Bacteriophages (phages) are viruses that infect bacteria,
of proteins, there are pumps that are considered to be and there is a current move to bring “phage therapy” to
specialized for exporting heavy metals (silver, cadmium, Australian hospitals in order to treat AMR infections. But
mercury, etc.), small toxic molecules (polyamines, where will these therapeutic phages come from? This
disinfectants, biocides in hand-soaps, etc) and antibiotic project aims to assess phage diversity through a classical
drugs. However, there is a growing awareness that efflux environmental microbiology approach: using water samples
pumps are not always so substrate-specific and that some collected from diverse locations around the world, the
efflux pumps annotated as, for example “silver efflux” are phages therein will be concentrated and plated on a lawn
also capable of exporting antibiotic drugs. This project would of bacteria. Attention will be focused on phages that infect
take multiple approaches for predicting the effects of efflux the pathogens K. pneumoniae or S. aureus, particularly on
pumps on the evolution of AMR: in terms of their predicted the carbapenem-resistant forms of K. pneumoniae (CRE)
structures using AlphaFold, their evolutionary relationships and the methicillin-resistant forms of S. aureus (MRSA).
to one another using comparative genomics, and in terms of Using a combination of electron microscopy to assess
their distribution in the prevalent AMR superbugs, E. coli and virion morphology, and bioinformatics for comparative
K. pneumoniae, particularly their carbapenem-resistant forms genomics and protein identification, the project would
(CRE). Using E. coli as a model superbug, a set of efflux classify, catalogue and compare the various phage
pumps active for exporting biocides in hand-soaps will be isolated. Finally, a systematic assessment of cocktails of
tested for their activity in exporting antibiotic drugs. the various phage will be undertaken to determine killing
efficacy for future therapeutic work, driven by the Phage
Australia Network (https://phageaustralia.org/).

Professor Dena Lyras
EMAIL dena.lyras@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9902 9155
Professor Dr Yogitha Srikhanta Dr Steven Mileto Dr Milena Awad A/Professor Dr Melanie Hutton Dr Sarah Larcombe
Dena Lyras Priscilla Johanesen
Understanding the Host Repair Response Anti-sporulation strategies targeting

to Clostridioides difficile Infection spore-forming pathogens
Professor Dena Lyras, Dr Melanie Hutton and Professor Dena Lyras and Dr Yogitha Srikhanta
Dr Steven Mileto
Spore-forming bacteria include the devastating human and
Gastrointestinal infections often induce epithelial damage that animal pathogen Clostridioides difficile, the food spoilage
must be repaired for optimal gut function. While intestinal pathogen Bacillus cereus and the agent for bioterrorism
stem cells are critical for this regeneration process, how they Bacillus anthracis. Spores are the infectious particles of these
are impacted by enteric infections remains poorly defined. pathogens and their resistant and unique structure makes
We recently investigated infection-mediated damage to them difficult to eradicate. Their persistence properties
the colonic stem cell compartment and how this affects enable the spread of disease, resulting in fatalities and
epithelial repair and recovery from infection, using the economic devastation in environments such as health care
pathogen Clostridioides difficile, which induces a spectrum settings, the food industry and public spaces in the case of
of diarrheal diseases mediated by two exotoxins, TcdA and weaponised anthrax. Despite these major problems, there
TcdB. These toxins share sequence and structural homology are no strategies to prevent spore production. C. difficile
but may contribute to disease severity unequally. We have is of considerable medical interest due to the high disease
shown that infection disrupts mouse intestinal cellular burden and global challenge of managing the consequences
organisation and integrity deep into the epithelium, and of infection. C. difficile spores are highly resistant to antibiotic
exposes the otherwise protected stem cell compartment. treatment and disinfectants and are responsible for facilitating
This disruption of the gut epithelium occurs primarily through disease transmission and recurrent infection. Our published
TcdB-mediated damage and altered stem cell signalling work has shown that cephamycins, a group of beta-lactam
and function, resulting in a significant delay in recovery and antibiotics, can inhibit spore formation of C. difficile epidemic
repair of the intestinal epithelium. However, the mechanisms isolates by blocking the activity of spore-specific penicillin
of stem cell intoxication, and the effects of different TcdB binding proteins. Of clinical relevance, co-treatment of
variants on stem cell function, remain unknown. Animal mice with the cephamycins and the standard-of-care C.
models of infection will be used, together with specific C. difficile treatment vancomycin, which is ineffective against
difficile mutants and strain variants, to study virulence factors spores, prevented recurrent infection. This project will
and host interactions, allowing us to gain a mechanistic extend our C. difficile spore formation inhibition studies to
understanding of how these bacteria interact with, and other spore-forming bacteria, including both pathogens and
damage, the host gut. We will also use various tissue culture commensals, to work towards better drug delivery strategies
systems to examine the specific molecular mechanisms that for treatment of diseases caused by these pathogens.
lead to TcdB-mediated stem cell dysfunction, including stem
cell-derived organoids.

Interrogating the effects of the Understanding the Role of Bacterial
human host protease plasminogen on Structures in the Transfer of Antibiotic
Clostridioides difficile infection Resistance Genes During Conjugation
Professor Dena Lyras and Dr Milena Awad Professor Dena Lyras, Dr Yogitha Srikhanta,
Dr Sarah Larcombe and A/Professor Priscilla
The human and financial cost of Clostridioides difficile global Johanesen
epidemics is substantial and alarming, with C. difficile listed
as the number one antibiotic-resistant bacterial threat in The treatment of bacterial infections in animals and humans
the USA. A key driver of C. difficile infection relates to the has relied on the use of antibiotics for over 50 years.
ability of this bacterium to form spores, an inert and highly However, one consequence of the use of these drugs is
robust cell type, which allows survival of the bacterium in antibiotic resistance, which is now one of our most serious
hostile environments. Spores initiate and transmit disease, global health threats. Bacteria can become resistant to
and contribute to disease relapse, whereas the vegetative antibiotics through the lateral transfer of resistance genes,
cell form of C. difficile colonises the gut and produces which are often located on mobile genetic elements such
potent toxins that cause disease. We have found that the as plasmids and transposons. This project will focus on a
host protease plasminogen migrates to the gut following mechanism of lateral gene transfer known as conjugation,
toxin mediated damage and that C. difficile spores, but which involves direct cell-to-cell contact and transfer of
not vegetative cells, recruit plasminogen to their surface. genetic material through bacterial structures known as
Importantly, we have also shown that the active form conjugative pili. Apart from the conjugative pili, very little is
of plasminogen (plasmin) modifies the spore surface, known about the role that other bacterial surface structures
increasing the germination rate and leading to a faster play in conjugation. Here, we will examine the role of
production of toxin-producing cells that culminates in disease numerous bacterial structures in DNA transfer efficiency
exacerbation. In this project, we will further interrogate the using molecular techniques, which may identify new
effects of this alteration to the spore surface using cutting- therapeutic targets and strategies through which the spread
edge imaging technologies such as STimulated Emission of antibiotic resistance can be inhibited.
Depletion (STED) microscopy and immuno-electron
microscopy, and will further explore the contribution of these
spore surface modifications to C. difficile infection.

Associate Professor Sheena McGowan
EMAIL sheena.mcgowan@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9902 9309
WEB https://www.monash.edu/discovery-institute/mcgowan-lab/home
A/Professor Sheena McGowan Dr Chaille Webb Dr Chathura Suraweera
The McGowan laboratory is interested in characterising Development of Phage Lysins

new drug targets. The lab has a strong research focus in
the design of novel anti-malarial drugs as well as other
as Novel Antimicrobials
parasitic and bacterial diseases. Primarily we are a structural A/Professor Sheena McGowan and
microbiology laboratory using techniques in protein structural Dr Chathura Suraweera
biology, biochemistry and molecular biology to analyse drug The growing problem of antibiotic resistance underlies the
targets of interest. We use this mechanistic information to critical need to develop new treatments to prevent and
design inhibitors or analogues with potential applications control resistant bacterial infections. Exogenous application
in human medicine. The laboratory has close connections of bacteriophage lysins to dormant and actively growing
with both the Department of Biochemistry and the Monash cell cultures results in rapid cell death. Understanding the
Institute of Pharmaceutical Sciences (in Parkville). mechanism of action will allow the development of lysins
The general projects are outlined below and interested as a next generation antimicrobial agent.
students are encouraged to contact Sheena with any
questions or to discuss further. Antimicrobial Effectors from
Acinetobacter baumannii
Penicillin Binding Proteins A/Professor Sheena McGowan and
of Clostridioides difficile Professor John Boyce
A/Professor Sheena McGowan and Acinetobacter baumannii is recognized as one of the three
Dr Chaille Webb most important Gram-negative hospital-derived pathogens.
The human pathogen Clostridioides difficile produces spores A. baumannii isolates resistant to all available antibiotics have
as part of the bacteria’s mechanism of survival when already been identified in patients and there is an urgent
confronted by antibiotics that lead to recurrent and need to find new methods to control A. baumannii infections.
debilitating infection particularly in hospital environments. We Interestingly, A. baumannii encodes an arsenal of lethal toxins
have discovered a set of penicillin binding proteins normally designed to directly kill competing bacteria and we believe
responsible for the biosynthesis of the bacterial cell wall that that these toxins are a rich source of new antibacterial
are also required for the formation of spores. This project molecules. This project aims to characterise the structure
will advance our understanding of the link between antibiotic and function of these novel toxins and assess their suitability
use and sporulation, and provide a path to new drugs for as potential new antimicrobials.
prevention of sporulation.

A New Drug Class for Malaria
A/Professor Sheena McGowan and Dr Chaille
Webb
are essential for parasite survival.
Malaria is a potentially fatal disease caused by infection with Three of these enzymes, known as M1, M17 and PfAPP,
Plasmodium parasites and threatens almost 40% of the are validated and attractive drug targets. Agents that
global population. Management of malaria relies on prompt inhibit the activity of these enzymes thus represent leads
treatment with antimalarial medicines, but resistance has for the development of new anti-malarial drugs. We work
now emerged to all antimalarial drugs in clinical use. The closely with our collaborators at the Monash Institute of
McGowan laboratory leads a large and advanced structure- Pharmaceutical Sciences and have multiple project(s)
activity based drug design program targeting the Plasmodium available that aim to develop detailed structural and
metallo-aminopeptidases which are protease enzymes that functional models of the mechanism of action of these
new drug targets and use this information in the design
and development of inhibitors as novel pre-clinical drug
candidates.

Associate Professor Greg Moseley
EMAIL greg.moseley@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9905 1036
Immunofluorescence
microscopy (upper
panel) and 3D dSTORM
super-resolution
imaging (lower panel) of
the cellular microtubule
cytoskeleton associated
with viral protein reveals
significant differences
between proteins of
lethal (left) and non-
lethal (right) viral strains.
A/Professor Greg Moseley
Viruses pose one of the grand challenges to human and Elucidating the Rabies Virus P Protein Axis
animal health globally and within Australia. Viral disease
progression is critically dependent on the formation of A/Prof Greg Moseley, Dr Stephen Rawlinson and
Ms Cassandra David
specific interaction networks between viral proteins and
host cell factors, which enable viral subversion of important Rabies is a currently incurable disease that has the highest
cellular processes such as antiviral immunity and cell survival. fatality rate of known infectious diseases. The etiological
agents of rabies are lyssaviruses, such as rabies virus and
We use advanced cellular/molecular biology approaches
Australian bat lyssavirus. Despite a very limited genomic
including quantitative proteomics, structural biology,
capacity these viruses are able to mediate replication,
functional genomics, immune signalling assays, and live-cell/
assembly and budding, while simultaneously arresting
super-resolution imaging to elucidate these interactions at
potent control over the infected cell and host immunity.
the molecular and cellular level, and viral reverse genetics
Central to this are multifunctional proteins including P
and in vivo infection models to define their functions in
protein, which resides at the core of the virus-host interface,
disease.
forming a myriad of interactions with viral and host proteins.
Our major focus is on highly lethal human viruses including We showed that by inhibiting such interactions, we can
rabies/lyssaviruses, Nipah, Hendra, SARS-CoV-2 and Ebola prevent otherwise invariably lethal disease, identifying
virus, as well as a number of agriculturally significant and the P protein ‘axis’ as a therapeutic target. However, the
potentially zoonotic animal viruses. The overarching aim of molecular/structural mechanisms by which this small
the research is to identify new strategies for the development protein coordinates/regulates its diverse interactions remain
of novel vaccines and therapeutics for currently incurable unresolved, leaving major gaps in knowledge concerning
diseases. Beyond disease, we also research the biology of fundamental processes in a lethal human disease.
so-called “Giant Viruses” that straddle the boundary between
The project will seek to define the specific molecular surfaces
living cells and “non-living” viruses, to better understand this
mediating key interactions of P protein, and to analyse
potential fourth domain of life.
their function using mutagenesis. This will contribute to the
The research involves extensive collaborations within Monash elucidation of the structural organisation and regulatory
University and other leading national (e.g. University of mechanisms of the virus-host interface and help to define
Melbourne, CSIRO-ACDP high-containment facility) and novel mechanisms by which viruses efficiently co-regulate
international institutes (e.g. Pasteur Institute, Paris; Gifu and host cell subversion and replication. These findings have
Hokkaido Universities, Japan; IITB, Mumbai, India), enabling the potential to redefine our understanding of the virus-host
access to unique resources and technologies including novel relationship and to provide critical tools and data for the
and highly pathogenic viruses. development of new vaccines and antivirals.

Viral Reprogramming of Host biochemical ‘spark of life’. We are also examining how giant
viruses interact with other microbes, and the implications for
Cell Signalling their biology and evolution.
A/Prof Greg Moseley, Dr Stephen Rawlinson and
Ms Cassandra David Super-Resolution Analysis of the
Central to the spread of pathogenic viruses is their capacity Virus-Host Interface
to interfere with host immunity, in particular the antiviral A/Prof Greg Moseley and Dr Toby Bell
system mediated by cytokines such as the interferons. It is
Viruses are experts at remodelling the infected cell, and
well known that many viruses target interferon signalling to
can fundamentally alter cellular biology to transform host
shut down the expression of antiviral genes. However, our
cells into efficient virus factories. Although molecular/
recent work indicates that the interaction of viruses with
biochemical evidence indicates that certain viral proteins can
cytokine signalling pathways is much more complex and
functionally modify structures such as the mitochondria, cell
intricate, involving interaction with multiple cytokine signalling
membranes, the nucleus and cytoskeleton, understanding of
pathways through a number of mechanisms including the
the physical effects on these structures is limited due to the
remodelling of cellular structures of the cytoskeleton and
poor resolving power of standard cell imaging approaches.
nucleus. Importantly, mutagenic analysis and viral reverse
Using single molecule localization techniques to surpass the
genetics, indicates that altering viral targeting of these
physical diffraction limit of visible light, we have developed
pathways profoundly inhibits pathogenesis in vivo, indicative
methods to observe and quantify the effects of viral
of critical roles in disease. We are currently seeking to
proteins on cellular structures at super-resolution, enabling
delineate the precise mechanisms by which viruses, such as
us to directly measure viral remodelling of the subcellular
rabies, SARS-CoV-2 and Ebola interfere with and modulate
environment. Using this approach, we demonstrated that
cellular pathways, not only to inhibit antiviral signalling, but
virus protein targeting of the cytoskeleton correlates with the
also to reprogram specific signalling pathways toward ‘pro-
capacity to cause lethal disease in vivo. The project will apply
viral’ responses, a novel concept in viral biology.
state-of-the-art single molecule localization techniques such
as 3D dSTORM to define viral effects on cellular structures in
Can Rabies Cure Alzheimer’s? unprecedented detail; this will provide new insights into the
A/Prof Greg Moseley, Dr Stephen Rawlinson and ways that viruses co-opt cellular function to cause disease.
Ms Cassandra David
Neuroinflammation is a major factor in human pathologies Why do Cytoplasmic RNA Viruses
such as stroke, Alzheimer’s disease (AD), and traumatic Target the Nucleolus?
brain injury (TBI). Viruses such as rabies/lyssaviruses,
A/Prof Greg Moseley and Dr Stephen Rawlinson
paramyxoviruses Nipah, Hendra, measles, coronaviruses,
and Ebola virus, have evolved powerful mechanisms to shut Many diverse viral proteins have evolved independently to
down inflammatory signalling for immune evasion. We aim target the nucleolus but this phenomenon had been largely
to discover the molecular ‘tricks’ used by viruses to subvert overlooked, particularly for RNA viruses that replicate within
host immunity, and to harness these mechanisms to develop the cytoplasm. Following the development of advanced
new methods to prevent inappropriate responses underlying ‘systems-biology’ approaches to analyse nucleolar biology,
neuroinflammatory disorders and other diseases including it has become clear that the nucleolus is complex, dynamic,
cancers. and highly multifunctional machine that coordinates many
critical cellular processes including immunity and cell survival.
This has redefined our understanding of the nucleolus and
Are Giant Viruses alive, and how do they suggests that the virus:nucleolar interface might represent
interact with other microbes? a central hub for viral hijacking of cellular processes,
A/Prof Greg Moseley and Ms Cassandra David important to viral replication and pathogenesis.
The recently discovered giant viruses inhabit a unique Using highly pathogenic RNA viruse, including rabies and
evolutionary space, somewhere between living biological Hendra virus, we are investigating the mechanisms by
organisms and non-living microbes. The evolutionary history which viruses can reprogram the nucleolus to alter cellular
and fundamental biological nature of giant viruses remain biology. These studies are identifying for the first time specific
poorly defined, including such fundamental questions as nucleolar functions for RNA virus proteins. The project will
whether giant viruses are ‘alive’ and what these viruses utilize techniques including molecular biology, proteomics,
mean for our understanding of life. We recently initiated super-resolution microscopy, virus replication and gene
new studies of giant viruses in collaboration with the Indian expression assays, and gene knockout approaches to
Institute of Technology Bombay (IITB) using techniques delineate the precise events underlying cellular dysfunction
including super-resolution imaging and proteomics to caused by virus- nucleolus interaction.
understand the life cycle of these viruses and their structure
and to define whether giant viruses have evidence for a

Professor Hayley Newton
EMAIL hayley.newton@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9902 9159
Coxiella (red) replicates in a

spacious lysosome-derived
vacuole (green = lysosomal
membrane protein).
Anton Peleg
Professor Hayley Newton Dr David Thomas
Defining the mechanisms of lysosome spectrometry will be employed to identify the host targets
of this pathogen protease. Techniques used in this project
survival by Coxiella burnetii will include genetic manipulation of C. burnetii, cell culture
Professor Hayley Newton and Dr David Thomas infection and transfection, immunofluorescence confocal
Our laboratory aims to create new knowledge in host- microscopy, protein biochemistry, mass spectrometry and
pathogen interactions driven by intracellular bacterial molecular biology.
pathogens. Our research team has projects on Coxiella
burnetii, Legionella species, Salmonella enterica and Characterisation of effector proteins that
other intracellular bacterial pathogens. We are fascinated block human cell death
by Coxiella burnetii, the causative agent of Q fever, and
Professor Hayley Newton and Dr David Thomas
Legionella species, the causative agents of Legionnaires’
disease, which replicate inside human cells in a manner that Coxiella burnetii employs a cohort of Dot/Icm effector
requires the Dot/Icm type IV secretion system. This multi- proteins to block human host cell death allowing the
protein apparatus delivers a huge number of novel effector pathogen to slowly replicate to large numbers intracellularly.
proteins into human host cells, manipulating many aspects of We have preliminary data supporting a role in preventing
human cell biology, to facilitate intracellular replication of the host cell death for several novel C. burnetii effector proteins,
pathogen. However, very little is known about how individual but we do not yet understand their mechanism of action.
effectors influence pathogen success. This project will characterise one of these cell death blocking
effectors by:
The Dot/Icm type IV secretion system is central to the
ability to establish a replicative niche within the human cell i) determining changes to infection dynamics associated
lysosome. However, even without this system C. burnetii can with the absence of this effector
survive the degradative, hostile conditions of the lysosome.
ii) examining the protection this protein offers human cells
The key traits that make C. burnetii resistant to lysosomal
from different cell death stimuli
killing remain unknown. This project will begin to examine
the dynamics of C. burnetii lysosome resistance and develop iii) identifying and characterising interactions between this
a screening strategy for identifying bacterial factors that effector and its host cell targets
contribute to survival. Additionally, this project will examine This project will involve immunofluorescence confocal
the role of a specific C. burnetii protease that has been microscopy, protein biochemistry, mass spectrometry,
shown to be secreted into the Coxiella-containing vacuole. molecular biology and the use of cell culture for infections,
A mutant unable to make this protease will be examined cell death assays and transfections.
in tissue culture models of infection and specialised mass

Professor Anton Peleg
EMAIL anton.peleg@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9902 9159
Professor Anton Peleg Dr Margaret Lam Dr Faye Morris Dr Xenia Kostoulias Dr Jhih-Hang Jiang
MECHANISMS OF PATHOGENESIS OF Project 1

HOSPITAL-ACQUIRED ORGANISMS The aim of this project is to characterise the mechanisms
of MRSA adaptation and evasion to antibiotic and host
Impact of Antibiotic Resistance on Immune innate immune attack. The work will comprehensively
Recognition of Staphylococcus aureus identify genetic mutations that confer a survival advantage
to MRSA under daptomycin pressure in the context of an
Dr Jhih-Hang Jiang and Professor Anton Y. Peleg immune response. This will be achieved by exposing clinically
S. aureus is one of the most common human bacterial relevant MRSA strains to both antibiotic and host immune
pathogens, and is able to cause a wide range of life- selection pressure, and apply a novel sequencing approach
threatening infections in the community and hospital setting. to characterise the full repertoire of mutations in specific
As a consequence of the rising rates of methicillin-resistant phospholipid biosynthesis genes known to be important
S. aureus (MRSA), agents such as vancomycin and daptomycin for antibiotic resistance. The significance of the identified
have been increasingly relied upon. Unfortunately, reduced mutations will be assessed by making independent mutants
susceptibility to these agents has now emerged. By using using our well-developed targeted mutagenesis system.
large-scale, whole-genome sequencing of clinical S. aureus The impact of individual mutations on antibiotic resistance,
isolates, whereby the first isolate is susceptible and the paired staphylococcal virulence, bacterial membrane biogenesis
isolate is non-susceptible, we have been able to describe and host immune responses, will be assessed. This project
the genetic evolution of antibiotic resistance in patients. will combine exciting bacterial genetic techniques and
Interestingly, we have also identified, using both mammalian advanced biochemical approaches together with novel
and non-mammalian model systems that these resistant infection model systems.
strains have altered host-pathogen interactions, and appear
to be more persistent.

Project 2 How does plasmid transmission drive
In collaboration with Professor Meredith O’Keeffe antibacterial resistance and virulence in
(Dept. of Biochemistry) the clinic and the environment?
The aim of this project is to characterise the activation of Dr Margaret Lam and Professor Anton Peleg
pathogen recognition receptors by our paired susceptible
Plasmid transmission between bacteria of the same or
and resistant clinical isolates. This will be achieved by
different species is an important driver of genetic diversity,
studying one of the key first responders of our immune
bacterial adaptation and evolution. In the clinical setting, the
system; dendritic cells. Different dendritic cell types differ in
transmission of plasmids between hospital pathogens such
their expression of pattern recognition receptors and hence
as K. pneumoniae plays a critical role in the dissemination of
the types of pathogens that they recognise. They also differ
virulence and antimicrobial resistance (AMR) genes that can
markedly in their subsequent innate response to pathogens,
subsequently imbue strains with the ability to cause invasive
with discrete dendritic cell subsets specialised in the
and untreatable infections. Outside of the clinical setting,
production of different cytokines and interferons. This project
bacterial samples from animal and environmental sources are
will focus on the differences in pathogen recognition and the
also enriched with plasmids, and alongside the occasional
subsequent immune activation between clinically important
detection of AMR genes, also encode for other lifestyle-
and drug-resistant S. aureus strains. Using established
enhancing traits such as heavy metal resistance or virulence.
S. aureus mutants, we will also determine the impact of
changes in bacterial surface characteristics on activation of Differences in plasmid distributions across the bacterial
pathogen recognition receptors. population and within different sampling niches highlight
complexities in both the transmission dynamics of different
Characterising Novel Virulence Mechanisms plasmids and the varying ability of bacterial strains to
uptake and maintain plasmids. For example, the AMR
in the Emerging Hospital-Acquired plasmids are detected at higher frequencies in the
Pathogen; Acinetobacter baumannii bacterial populations that circulate and cause outbreaks in
Professor John Boyce, Dr Faye Morris and hospitals. While comparative genomics and experimental
Professor Anton Peleg evolution experiments have so far provided some insights
into both bacterial and plasmid mechanisms responsible
Small RNA (sRNA) molecules play important roles in
for this variation in transmission, many questions remain
the regulation of a wide range of bacterial phenotypes
unanswered.
including virulence. Together with Dr Gerald Murray we have
previously determined which A. baumannii sRNA molecules This project will use techniques within the comparative
are expressed in vivo during a mouse infection model. We genomics space to examine how plasmid loads and types
predict that sRNAs expressed at high levels in vivo will have vary across Klebsiella strains from different sampling origins
a role in regulating A. baumannii virulence factors. We have (i.e. clinical vs non-clinical) and genetically distinct lineages.
generated an assortment of individual sRNA mutants and in These insights will be important for identifying ‘high risk’
this project, we will select those that are highly expressed species, lineages or plasmids that have higher plasmid
in vivo and complement the mutants by generating individual transmission/maintenance rates, and therefore may be
constructs expressing the relevant sRNA from different important targets in genomic surveillance or transmission
promoters. By comparing our repertoire of strains (ie sRNA intervention strategies.
mutants, complements and overexpression strains) we
This project will largely utilise techniques in the genomics
will analyse the effects on a range of virulence-associated
space including, but not limited to, de novo genome
phenotypes (growth in human serum, biofilm formation,
assembly and annotation, DNA sequence alignments,
and mouse infection models), with a view to identify and
building phylogenetic trees and BLAST. The work is therefore
confirm the sRNA specific targets using high-throughput
suitable for students with an interest in computational biology
proteomics and RNA sequencing of sRNA-mRNA duplexes.
and its application in studying bacterial pathogens.
Where inactivation of an sRNA affects virulence, we will
design and construct sRNA inhibitors and test these as novel
antimicrobials.
Note: Working with animals is not compulsory for any of the

advertised projects.

Dr Francesca Short
EMAIL francesca.short@monash.edu
ONE VACANCY
TELEPHONE +61 3 9902 9282
WEB https://research.monash.edu/en/persons/francesca-short
Dr Francesca Short (Left) Capsule regulation network of hypervirulent Klebsiella pneumoniae, constructed from high-throughput mutant profiling
(Right) Strain-dependence of serum resistance in diverse K. pneumoniae isolates
Functional genomics to understand Characterisation of novel iron regulators in K.

bacterial virulence control and adaptation pneumoniae
Dr Francesca Short and Dr Faye Morris K. pneumoniae is one of the most devastating pathogens of the
My research focuses on understanding virulence and antibiotic resistance crisis. This bacterium produces up to four
antimicrobial adaptation in two Gram-negative ‘superbugs’ - distinct iron-stealing siderophores, which collectively determine the
Acinetobacter baumannii and Klebsiella pneumoniae. These course and severity of infection. We have performed high-throughput
bacteria require specific virulence factors such as protective functional genomic screens to identify novel transcriptional regulators
capsule and iron-stealing siderophores for pathogenesis, contributing to iron acquisition in K. pneumoniae. This project will
but we have a very limited understanding of the molecular explore the function of one of these newly-identified regulators to
decision making that controls and coordinates these factors. find out what genes it controls, how it is distributed across the K.
My primary research focus is to address these knowledge pneumoniae population, and how this regulator affects virulence and
gaps in order to improve prediction of phenotype from related phenotypes.
genotype in bacterial pathogens, and open the way for the
Understanding the collateral damage of
development of new virulence-subverting drugs.
benzalkonium chloride disinfectants
My second research interest focuses on the connections
Recent research from our group and others has revealed that
between disinfectant use and antimicrobial resistance.
indiscriminate disinfectant use may be a hidden driver of antibiotic
Disinfectants are essential for infection control but are poorly
resistance for two reasons: 1) Adaptation to disinfectants often
regulated, and there is increasing evidence that their use may
causes cross-resistance to certain antibiotics, and 2) Some
be a hidden driver of AMR. I aim to understand the short-
disinfectants, when present, can directly antagonise antibiotic killing.
and long-term consequences of disinfectant exposure on
This project will examine the effects of the widely used synthetic
target bacteria in order to prevent usage that compromises
disinfectant - benzalkonium chloride - on the notorious hospital
antibiotics. In all of my research I combine high-throughput
pathogen Acinetobacter baumannii. The trajectory of disinfectant
genomic approaches with classic “wet-lab” microbiology to
adaptation will be defined under realistic exposure modes, and the
define the mechanisms underpinning bacterial behaviour. My
consequences of these changes for antibiotic treatment will then
research is funded by an ARC DECRA fellowship.
be investigated. These long-term effects will then be matched with
measures of direct benzalkonium chloride-antibiotic antagonism to
build a complete picture of the interplay between this disinfectant,
antibiotics, and the microbes they target.

Associate Professor Anna Roujeinikova
EMAIL Anna.Roujeinikova@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9902 9194
Associate Professor Anna Roujeinikova H. pylori CA-inhibitor complex Chemoreceptor sensory domain
Structural Studies of Virulence Dissecting Architecture of

Factors of the Carcinogenic Bacterium High Torque Bacterial Motor
Helicobacter pylori The bacterial flagellar motor is a remarkable nanoscale
Helicobacter pylori persistently colonize the epithelium of molecular engine. H. pylori evolved to be highly motile in the
the stomach in roughly half of the world’s population. It is very viscous mucous layer of the stomach, and its flagellar
a causative agent of gastric and duodenal ulcers, mucosa- motor is specialised for locomotion in viscous liquids – it
associated B-cell lymphoma and gastric adenocarcinoma. produces a significantly higher torque (turning force) than, for
example, enteric bacteria. Preliminary cryo-electron tomography
Although it is a definitive carcinogen, there is no effective vaccine reconstruction of this motor revealed a unique protein cage
against this bacterium. Standard H. pylori eradication therapy that supports a wider power-generating ring allowing it to
now fails in up to 30%-40% of patients, mainly due to an increase sustain the larger torque. Our aim is to unravel the make-up
in clarithromycin resistance. There is a clear demand for new of this cage and the structural basis for its ability to recruit
strategies to fight H. pylori infections, strategies that involve new more force-generating units.
or unconventional targets for drug design. A key to success
with this lies in strong basic knowledge of the molecular basis
of bacterial virulence and survival. Our laboratory focuses on the How do Bacteria Sense
mechanisms of acid acclimation, damage to gastric epithelial Environmental Cues?
cells and motility and chemotaxis. We use in vitro molecular Many bacteria are motile. Chemotaxis, mediated by
biophysics and crystallography techniques to investigate structure chemoreceptors, plays an important role in bacterial survival
and dynamics of biomolecules and formulate hypotheses and virulence. In this project, we shall investigate what
about molecular mechanisms, which we then test in vivo ligands such receptors recognize and why some molecules
using genetics, enzymology and cell biology methods. are attractants and some repellents, how binding to the
receptor leads to signalling, how mutations in the sensor
domain affect ligand specificity and, building on this, how
bacterial chemoreceptors can be redesigned to recognize
and respond to non-native ligands for innovative applications
in biotechnology and bioengineering.
Applications are welcome from students with a strong

interest in structural biology, X-ray crystallography, the
biology of H. pylori, or protein biochemistry.

Professor Stephen Turner
EMAIL stephen.j.turner@monash.edu
ONE VACANCY
TELEPHONE +61 3 9902 9138
OFFICE 19 Innovation Walk (Building 76)
WEB https://www.monash.edu/discovery-institute/turner-lab
Assessing the Role of NOTCH Signalling in

Regulating Influenza-Specific Killer T Cell
Immunity
Virus infection triggers large-scale changes in the phenotype
and function of CD8+ killer T cells and are critical for
effective immune function; however, the precise gene
regulatory mechanisms that control these changes are
largely unknown. NOTCH is a cell surface receptor that is
involved in regulating cell fate decisions in multiple systems.
It mediates this via activation of a transcription factor called
RBP-J. While NOTCH signaling is reported to be important
for optimal virus-specific CD8+ T cell responses, the
molecular mechanisms that underpin this regulation are not Activation of NOTCH receptor by NOTCH ligands,
such as delta-like ligand (DLL) family members,
known. Our lab has recently shown that inhibition of NOTCH results in activation of the NOTCH signaling pathway.
signaling can impact acquisition of CD8+ T cell function. This Upon activation, the NOTCH receptor is cleaved by
a protease called γ-secretase, which releases the
project aims to use mice where RBP-J deletion is limited to NOTCH Intracellular Cytoplasmic Domain (NCID). This
CD8+ T cells to assess the impact of RBP-J deficiency on is a transactivating protein that is transported to the cell
nucleus where it pairs with RBP-J and another DNA
influenza A virus-specific T cells responses. This project will binding protein called Mastermind-like (MAML). This
use a combination of virology, cellular immunity, molecular complex then activates transcription of target genes.
This project will examine the impact of RBP-J deficiency
biology and biochemistry to assess the impact of RBP-J
on CD8+ T cell activation after virus infection.(Figure
deficiency on influenza A virus-specific killer T cell function adapted from Totaro et al., Trends in Cel Biology,
and establishment of immunological memory. 2018).

Projects Based at
Affiliated Institutions

2023
Hudson Institute of Medical Research
Professor Richard Ferrero

richard.ferrero@monash.edu or
EMAIL
richard.ferrero@hudson.org.au
TWO VACANCIES
TELEPHONE +61 3 9282 2111
OFFICE Hudson Institute of Medical Research, 27-31 Wright St, Clayton
WEB hudson.org.au/gastrointestinal-infection-and-inflammation/
Professor Richard Ferrero H. pylori bacteria (green) within a gastric organoid. (Images courtesy of L. S. Tran and G. Kerr)
Defining the Role of a Novel NLR Protein Characterisation of the

in Stomach B Cell Lymphoma Associated Immunomodulatory and Oncogenic
with Chronic Helicobacter Infection Properties of Bacterial Extracellular
Professor R. Ferrero Vesicles
Our laboratory has identified a new NOD-like receptor (NLR) Professor Richard Ferrero
protein in the regulation of inflammation in responses to The release of extracellular vesicles (EVs) is a property
chronic Helicobacter pylori infection. Specifically, we have that has been conserved by both multi- and unicellular
shown that conditional knockout mice lacking this NLR organisms during evolution. One of the major functions of
exhibit an accelerated formation of gastric B cell mucosa- these EVs is to facilitate intercellular communication and
associated lymphoid tissue (MALT), consistent with the transport of molecules. The release of EVs by prokaryotes
early stages of MALT lymphoma, in response to chronic was first described over 50 years ago, yet the biological
Helicobacter infection. We are now investigating how this significance of these structures is only beginning to be
novel NLR prevents B cell lymphomagenesis induced by appreciated. We have shown that bacterial EVs are potent
chronic infection and whether this protein may play much modulators of host immune responses. Several projects are
broader functions in the host immune system. A particular available to investigate how bacterial-derived EVs target the
focus of current studies is the role of NLRC5 in regulating nucleus, interfere with host cell functions and even promote
anti-tumour immune responses. These studies will be oncogenesis. These projects will involve cell culture and,
undertaken using both in vitro and in vivo models, including potentially, mouse models to elucidate EV interactions with
conditional knockout mice. The project will involve various host cells and to characterise the responses induced by EVs.
techniques, such as primary cell culture, mouse infection, A variety of techniques will be used, including cell culture,
immunohistochemistry, flow cytometry, cytokine ELISA and mouse models, proteomics, molecular biology, fluorescence
qPCR. imaging, flow cytometry, cytokine ELISA and qPCR.

Development of a Vaccine to Prevent
Stomach Cancer using Bacterial Vesicles
Professor Richard Ferrero
It is estimated that half of the world’s population have A vaccine against H. pylori infection would be the most
Helicobacter pylori infection. This bacterium lives in the cost-effective means of preventing stomach cancer.
stomach where it causes inflammation of the mucosa. Most Although vaccine trials in animals reported promising results,
individuals, however, do not know that they are infected. As a subsequent findings from clinical studies have generally been
consequence; stomach cancer is often diagnosed once the disappointing. The proposed project is directed at developing
disease is already advanced. Although antibiotic therapies an entirely new type of vaccine based on bacterial vesicles.
are available to eliminate H. pylori infection, these are not This project will involve a variety of techniques, such as
always effective. Therefore, new approaches are needed to molecular biology, bacterial mutagenesis, cell culture, mouse
better manage the infection and associated disease. models, proteomics, fluorescence imaging, flow cytometry,
cytokine ELISA and qPCR.

Dr Sam Forster
EMAIL sam.forster@monash.edu
TWO VACANCIES
TELEPHONE +61 3 8572 2753
OFFICE Room L2.52, Hudson Institute of Medical Research, 27-31 Wright St, Clayton
WEB https://hudson.org.au/research-group/microbiota-systems-biology/
Dr Sam Forster Dr Emily Gulliver Dr Michelle Chonwerawong Human Gastrointestinal Bacteria
Understanding Microbiome Interactions

with the Innate Immune System
Dr Sam Forster and Dr Michelle Chonwerawong
The innate immune system is capable of intricately detailed Emerging research is demonstrating the importance of these
detection, differentiation and elimination of pathogenic bacterial communities in both maintaining health and causing
bacteria. However, the vast majority of bacteria encountered or exacerbating disease. We have recently developed novel
by our innate immune system are beneficial to health. Indeed, methods to grow the vast majority of bacteria from the
over 500 species of these commensal bacteria, containing gastrointestinal microbiota. This research has resulted in the
approximately 10,000-fold more genes than the human discovery of hundreds of novel species which require further
genome, exist in the human gastrointestinal tract alone. investigation. Combined with the established experimental
and computational expertise in the analysis of innate immune
signalling pathways, this project will include cutting-edge
microbial culturing techniques, cell culture assays and advanced
computational analysis to identify pro- and anti-inflammatory
bacterial species.
Students interested in experimental or computational

elements, will have the opportunity provided to develop skills
in both areas.

Discovery of Antibiotic Resistance Gene
Dispersal in the Human Microbiome
Dr Sam Forster and Dr Emily Gulliver
Antimicrobial resistance (AMR) is emerging at an alarming level, tract, there are 100 trillion bacteria, representing more than
rendering some bacterial infections untreatable and increasing 500 species, which are exposed to selection for antibiotic
dependence on last-line antibiotics. There is an urgent need to resistance during oral antibiotic treatment. The resistance
provide clinicians with the data to inform antibiotic selection that mechanisms in these commensal bacteria remain largely
will optimize treatment success, while minimizing the spread undefined, despite representing a significant, hidden source
of resistance-containing species and dispersal of antibiotic of antibiotic resistance genes that could be transferred to
resistance genes. pathogenic or other commensal bacterial species.
Despite the bacterial diversity within our microbiota, current We have recently developed methods to culture the vast
understanding of the genetic factors that confer resistance majority of the human gastrointestinal microbiota (Nature,
is almost exclusively limited to pathogenic or opportunistically 2016; Nature Biotechnology, 2019), which will provide an
pathogenic organisms. For example, in the human gastrointestinal important resource to undertake these studies. This project
will combine detailed genomic and metagenomic sequence
analysis with in vitro microbiology to understand and monitor
the diversity and distribution of antibiotic resistance within the
human gastrointestinal microbiota. The opportunity also exists
to focus the project to experimental or computational biology.

2023
Professor Elizabeth Hartland

EMAIL elizabeth.hartland@hudson.org.au
TWO OR THREE
TELEPHONE +61 3 8572 2800 VACANCIES
OFFICE Hudson Institute of Medical Research, 27-31 Wright St, Clayton
WEB hudson.org.au/research-group/innate-immune-responses-infection/
Left to right, Enteropathogenic E. coli adhering to epithelial cells and causing the rearrangement of actin (red)
underneath the adherent bacteria. Cell nucleus (blue). Electron micrograph showing the replicative vacuole of the
Legionnaire’s pathogen, Legionella pneumophila. Actin tail formation (red) by the intracellular bacterium, Burkholderia
thailandensis (green). Cell nucleus (blue).
Professor Elizabeth Hartland
Innate Reponses to Bacterial Infection that the EPEC T3SS effector kinases, NleH1 and NleH2
both specifically phosphorylate host EPS8, an actin bundling
The subversion of host cell processes by microbial protein that is enriched at the tips of microvilli. Despite the
pathogens is an intrinsic part of the host-pathogen important role of EPS8 in maintaining normal microvillus
interaction. Many bacterial pathogens have the ability to structure, the function of the protein and the basis of its
transport virulence proteins, called effector proteins, into localisation to the tips of microvilli is unknown. Since most
host cells via specialised protein secretion systems. We work studies of EPEC infection have not used cellular models that
on a range of virulence effectors from pathogenic E. coli, support microvilli, here we will use a polarized cell model of
Shigella, Legionella and Burkholderia species that interfere EPEC infection as well as human small intestinal organoids
with host innate immune responses. The aim of this work is to determine the role of NleH1 and NleH2 in microvillus
to investigate the manipulation of host cell signalling and cell effacement during EPEC infection. This project will inform
intrinsic immunity by effector protein families to understand our understanding of A/E lesion formation in complex human
their influence on host cell function, inflammatory signalling tissue and help to elucidate the role of EPS8 in microvillus
and the innate immune response. In this way effector function. This project will employ techniques such as
proteins can be used as tools to understand the innate bacteriology, human organoid culture, bacterial infection,
responses important for control of the pathogen. molecular biology, and high resolution microscopy.
The microvillus protein Eps8 as a target Targetting of host mRNA by the

of EPEC infection intracellular pathogen, Legionella
Professor E. Hartland, Dr C. Giogha, and Dr E. pneumophila
Chan
Professor E. Hartland, Dr K. McCaffrey and Dr R.
A hallmark of EPEC infection is the formation of attaching Wibawa
and effacing (A/E) lesions on the apical surface of host
Legionella pneumophila translocates more than 300 effector
enterocytes, which are characterised by the destruction of
proteins into the infected macrophage that manipulate a
microvilli and rearrangement of the host cell cytoskeleton
range of host cell processes. We have discovered that
at the site of bacterial attachment. We recently discovered
one effector protein induces the degradation of mRNAs

encoding enzymes involved in glycolysis. We hypothesise Ultimately this will allow us to understand the molecular
that the effector is a novel RNA-binding protein and that this mechanisms by which B. pseudomallei causes disease.
interference with host cell metabolism blocks the activation This project will employ techniques such as bacteriology,
of alveolar macrophages, where the switch to a pro- mass spectrometry, high-throughput screening, genetic
inflammatory phenotype coincides with increased glycolysis. modification of bacterial pathogens, cell culture, protein
This project will define the mechanism of action of the expression and purification, molecular biology, western blot,
anti-glycolytic effector protein and explore the impact of L. confocal microscopy and mouse models of infection.
pneumophila infection on macrophage metabolism. We will
also identify additional RNA-binding effectors from Legionella Discovering the biochemical activity of
and other intracellular bacteria. This project will employ
techniques such as bacteriology, protein biochemistry,
NleA family T3SS effectors
molecular biology, confocal microscopy, live imaging and Professor E. Hartland, Dr C. Giogha, Dr J. Gan and
mammalian cell infection, mouse infection models and Dr E. Chan
immunological analyses. The EPEC T3SS, NleA, is one of many effectors translocated
into host enterocytes during EPEC infection. However,
Understanding the role of T3SS effectors unlike other effectors, deletion of the gene encoding NleA
in Burkholderia infection strongly attenuates intestinal colonization by the pathogen.
Several host binding partners of NleA have been described,
Professor E. Hartland, Dr G. Ng and Dr R. Wibawa including the inflammasome protein, NLRP3 and Golgi
Melioidosis is a life threatening infection caused by the vesicle transport protein, Sec24. Despite this knowledge
environmental bacterium, Burkholderia pseudomallei. B. and the importance of NleA to EPEC virulence, the actual
pseudomallei has three T3SSs, one of which aids bacterial biochemical activity of NleA is unknown. Recent genome
escape from the phagosome into the cytosol. Despite studies have also shown that NleA effectors can be found
their significance in infection, relatively little is known about in Shigella and Salmonella species. Here we will apply
T3SS effector proteins and their role in melioidosis disease. advanced mass spectrometry techniques to identify possible
This project aims to identify T3SS effector proteins of post translational modifications of known binding partners
B. pseudomallei using a range of approaches, including of NleA. As nearly all experimental work to date on NleA has
bioinformatics to probe the B. pseudomallei genome for used non-intestinal and non-polarised epithelial cells, here
novel T3SS effector genes. We will develop assays and we will perform additional unbiased pulldowns from infected
proteomics based methods to identify effectors secreted intestinal organoids to and mass spectrometry identification
upon activation of the T3SS. Given our recent work on T3SS to identify novel NleA binding partners. This project will
effector proteins that dampen the host immune response, we employ techniques such as mass spectrometry, genetic
will prioritise screening for effectors that block inflammatory modification of bacterial pathogens, cell culture, protein
and cell death signalling. Effectors yielding interesting expression and purification, molecular biology, western blot,
phenotypes will be functionally characterised during infection. confocal microscopy, bacteriology and infection.

Dr Jaclyn Pearson
EMAIL jaclyn.pearson@hudson.org.au
ONE OR TWO
TELEPHONE +61 3 8572 2746 VACANCIES
OFFICE Room L2.45, Hudson Institute of Medical Research, 27-31 Wright St, Clayton
WEB hudson.org.au/researcher-profile/jaclyn-pearson/
Dr Jaclyn Pearson Salmonella Typhimurium replicating inside a Mouse intestinal organoids in culture
human macrophage
Research Focus
The focus of our research is to determine the mechanisms The model pathogen that we use in our research is Salmonella
by which bacterial pathogens interact with their host and to enterica. These pathogens are able to colonise a wide range
then use this information to understand the specific immune of human and animal hosts, and in humans, can cause disease
responses that are essential for fighting infections and ranging from gastroenteritis to systemic disease, depending
maintaining immune homeostasis in the body. on the Serovar of the bacteria. S. enterica serovar Typhi
and Paratyphi are human restricted and are known as the
Our overarching goal is to make discoveries on the
fundamental mechanisms of immunity to infections and to ‘Typhoidal’ Salmonella. These serovars cause serious illness
inform the future development of therapeutics for bacterial as the bacteria disseminate systemically, causing severe
infections and also, dysregulated immune responses in fever, nausea, diarrhoea, abdominal cramping and headaches,
inflammatory diseases. and if left untreated, death can occur.
Other non-typohoidal Salmonella serovars (NTS) include

S. enterica serovars Typhimurium and Enteritidis, both of
which account for the majority of gastrointestinal disease
(salmonellosis) in immunocompetent individuals worldwide.
In immunocompromised people; however, some NTS strains
cause invasive disease and thus more serious illness.

Understanding the Biochemical Mechanisms
of Salmonella Virulence Proteins
Dr Jaclyn Pearson and Professor Elizabeth Hartland
Pathogenic serovars of Salmonella are the causative agents
of a spectrum of disease states, including typhoid fever,
self-limiting gastroenteritis, and invasive bacteremia. Australia
has one of the highest incidences of Salmonellosis in the
developed world. Pathogenesis is dependent on the activity
of two distinct type III secretion systems (T3SS), encoded
by genetic regions termed Salmonella pathogenicity islands
(SPI). The SPI-1 T3SS is associated with bacterial invasion as
well as activation of innate immune signaling, and the SPI-2
T3SS is associated with intracellular survival in immune and
epithelial cells, replication and systemic infection. While the
importance of the SPI-1 T3SS to Salmonella pathogenesis
is well established, the function of many SPI-2 encoded
effectors remains unknown. This project aims to investigate
the role of a subset of relatively uncharacterised SPI-2
effectors in Salmonella virulence. Overall this project will
provide critical insights into the pathogenic mechanisms
of an important public health issue and provide the basis
for potential future therapeutic development.
Host Cell Death Signaling and

Susceptibility to Salmonella Infection
Dr Jaclyn Pearson and Dr Kate Lawlor
Enteric bacterial pathogens such as Salmonella spp. and
enteropathogenic E. coli deliver “effector” proteins directly into
host cells via specialised secretion systems which exert specific
enzymatic activity on host proteins to subvert host responses
and prolong infection. Our recent work characterised an
effector protein from pathogenic E. coli as a cysteine protease
that cleaves and inactivates all mammalian RIP homotypic
interaction motif (RHIM) proteins including RIPK1, RIPK3, TRIF
and DAI. RHIM proteins are key immune signaling factors that
mediate inflammation, apoptosis and necroptosis. Dysregulated
immune responses and cell death form the basis of much
human disease pathogenesis. This study aims to understand
the role of RHIM proteins in controlling Salmonella and other
enteric infections.

Department of Civil Engineering, Monash University
Associate Professor David McCarthy

EMAIL david.mccarthy@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9905 5068
OFFICE Room 120, Building 60
The EPHM RISE Settlement Suva
Environmental and Public Health Key to improving environmental and public health within
informal settlements is understanding the risk posed to
Microbiology Laboratory – EPHM Lab communities from pathogens transmitted through both
The EPHM Lab is located within the Civil Engineering human interaction and direct contact with soil and water
Department at Monash University, Clayton, and has a pathways.
specific focus on health-related urban water microbiology;
This project aims to quantify and understand the key
some of our projects include: (1) understanding the
pathways to transmission of a range of microbial (viral,
pathways pathogens follow in informal urban environments,
bacterial, protozoa and helminth) pathogens within 12
(2) development of passive sampling methods for use in
informal settlements within Makassar (Indonesia) and Suva
wastewater based epidemiology, (3) understanding the
(Fiji). You will also investigate the key drivers for transmission
human health risks caused by bacterial pathogens in water
including seasonality, temperature and rainfall, as well as
systems (reservoirs, rivers, ocean) and (4) understanding
human driven factors such as contact time and location
microbial community dynamics in complex environments.
of risk (within house, outside home). As part of our multi-
discplinary research team you will undertake laboratory-
Understanding Environmental Risks based analysis utilising quantitative PCR (qPCR) to quantify
in Informal Settlements concentrations of target environmental pathogens (including
A/Professor David McCarthy, Dr Rebekah Henry Escherichia coli, Shigella, Campylobacter, Salmonella and
(Dept. Civil Engineering) and Professor John Boyce Giardia) within a range of samples (soil, water, gloves).
(Dept. Microbiology) Samples will also be analysed using metagenomic and
16S bacterial community analysis to gain in depth insights
Informal settlements are home to more than a billion people.
into source and risks associated with a range of virulence
This number is growing annually in low and middle-income
factors and antimicrobial resistance genes. In doing so, key
countries such as Indonesia and Fiji. These communities
knowledge will be gained on pathogen dynamics within
often have limited or no access to sanitation services
informal settlements, key sources of contamination and
resulting in reduced environmental quality and public health,
pathways to transmission. The output will be used to inform
due to increased exposure to pathogens, pollutants, and
revitalisation strategies through implementation of targeted
disease vectors in air, water, food, and soil.
passive treatment technologies.

Wastewater Biosurveillance
A/Professor David McCarthy, Dr Rebekah Henry,
and Professor John Boyce
Human effluent has always been a major pathway to
infectious disease and epidemics. Recent publications
have reported multiple highly infectious viruses present
in water systems such in raw sewage and stormwater,
which detection offers a potential means of community
level surveillance. There are several barriers to the rapid
deployment of viruses monitoring programs. These include,
but are not limited to, the need for expensive equipment
and access to laboratories with specialized devices for
sample processing and molecular based diagnostics. In
addition, there are technical limitations in detection of low
concentration, but highly infectious agents in single one off
samples.
The development of low-cost, rapid and easily deployable

methods for long-term water systems monitoring were
an essential part of Victoria’s coronavirus response. And
demonstrated the need for these systems as part of holistic
responses to epidemics. As part of a multi-displinary team
you will work alongside microbiologists and engineers to use
your knowledge to aid the development and optimisation of a
field-ready passive sampling devise for long-term deployment
and monitoring of urban wastewater for a range of highly
infectious respiratory pathogens.
You will gain hands on experience in environmental

monitoring for microbial pathogens, isolation of virus and
other microbial pathogens from diverse sources, reverse
transcription PCR using currently applied global standards
and subsequent analysis. You will test your device alongside
standard and existing field- based methods, both within the
laboratory and field, to assess accuracy, precision, limits
of quantification and long-term stability of the device. Your
research will open opportunities for opimisation of sampling
devices and expansion of its capacity to absorb and retain
viral particles in water systems.
In undertaking this project you will gain key understandings

on the development of modern tools for remote monitoring
and sensing of key microbial pathogens. The output will be
directly applied to global environmental monitoring programs.

CSIRO Manufacturing
Dr Geoff Dumsday
EMAIL Geoff.Dumsday@csiro.au
ONE VACANCY
TELEPHONE +61 3 9545 2344
OFFICE CSIRO Manufacturing, Ian Wark Laboratory, Research Way, Clayton
Dr Geoff Dumsday
Biologically-Derived Synthons
for Chemical Synthesis
Dr Geoff Dumsday, CSIRO Manufacturing
White biotechnology (also known as industrial biotechnology) Our research centres on industrial biotechnology and
is the application of biotechnology in industrial processes. This aims to use microbial systems to specifically modify highly
cross-disciplinary emerging area of science is well placed to functional small molecules which can then be used as
play a key role in a sustainable future through: starting materials in a diverse array of chemical syntheses.
Using microbiological and molecular techniques, the student
(i) overcoming dependence on non-renewable feedstocks
will characterise microorganisms and enzymes that can be
such as crude oil,
used to produce synthetically useful compounds. Through
(ii) new environmental remediation technologies and the manipulation of growth conditions in both batch and
continuous culture, the student will use a range of analytical
(iii) a greatly reduced environmental footprint from
techniques (e.g. NMR and mass spectrometry) to identify
manufacturing. Broadly applicable across a range of market
and characterise metabolic products that are potential
sectors, many large companies are seeking to develop
chemical synthons. Of particular interest is the conversion
products and processes that are inspired by biological
of eucalyptus oil into chemicals that can be used to improve
systems and use renewable feedstocks such as terrestrial
the properties of polymers. This project will provide the
biomass to ensure their long-term future. Some example
student with the opportunity to engage with varied scientific
applications of white biotechnology already proven at
disciplines including industrial microbiology, molecular biology
an industrial scale include production of 1,3-propandiol
and organic chemistry and also an opportunity to work in
(DuPont), polylactic acid (NatureWorks LLC) and more
CSIRO’s state-of-the-art Recombinant Protein Production
recently isoprene (Dupont, Goodyear) to name but a few.
Facility.
Not only are these products derived from renewable
feedstocks, but the processes typically require less energy
input, less solvents and result in reduced levels of toxic
by-products.

Burnet Institute
Professor James Beeson

james.beeson@burnet.edu.au
EMAIL
chrissie.collins@burnet.edu.au
ONE VACANCY
TELEPHONE +61 3 9282 2111
OFFICE 85 Commercial Road, Melbourne (AMREP Campus)
Immunofluorescence microscopy showing Phagocytosis of malaria merozoites by a human

invasion of a human red blood cell by a monocyte, an important mechanism of immunity,
Professor James Beeson malaria merozoite (green) visualized using electron microscop
Developing Vaccines Against Malaria mediated immunity), flow cytometry, cell culture and protein
expression. The project could also include bioinformatics,
Malaria is one of the world’s leading causes of death and structural modelling of vaccine antigens, or modelling vaccine
illness, particularly among young children. There remains impact depending on the student’s interest. The specific
a strong need for highly effective vaccines to reduce the activities and focus of the project will be refined to suit the
burden of malaria and progress towards eventual malaria interests and training background of the student. Interested
elimination. To date, most vaccines have achieved only students should contact Chrissie Collins,
modest levels of efficacy, emphasising the need for novel chrissie.collins@burnet.edu.au
approaches in vaccine design that can induce potent
immune responses.
Discovering the Mechanisms and Targets
This project will focus on identifying key antigens and
of Immunity Against Malaria
specific epitopes that are targets of protective immunity
against malaria and understanding the mechanisms Antibodies are an important component of acquired immunity
mediating immunity, which includes antibodies and against malaria, as demonstrated in pivotal studies in which
cell-mediated responses. immunoglobulin G (IgG) from immune adults was transferred
to malaria-infected children and resulted in clearance of
This knowledge is crucial for the development of effective
infection. The mechanisms of protection and specific target
vaccines against malaria. The project will also involve using
epitopes of protective immunity are not well understood. In
knowledge of immunity to malaria for informing vaccine
recent studies, we have begun to uncover important roles
design, and the expression and testing of novel vaccine
for antibodies that can directly inhibit host-cell infection,
candidates. These studies will use novel approaches in
interact with immune cells to kill and clear malaria, or recruit
molecular biology, cell biology and immunology to address
complement to neutralise infection.
these aims, and will build on recent major advances generated
from our malaria vaccine program. The aims of this project include identifying the key targets
of specific mechanisms mediating immunity. The project
The project will primarily involve laboratory-based research,
may combine detailed studies of immune responses with
including western blotting, imaging, standard immunoassays,
clinical and population studies in Africa, Asia, and Papua
functional immunoassays (e.g neutralisation assays, cell-

New Guinea. It will examine how immune responses protect
children from malaria or protect pregnant women and their
developing babies from the devastating consequences of
malaria in pregnancy.
The studies would particularly focus on using innovative

approaches to understand how antibodies neutralise and
clear malaria parasites in the blood, including interactions
with monocytes/macrophages and dendritic cells, and
identifying specific epitopes targeted by protective antibodies.
Skills may involve assays of functional immunity, cell culture,
isolation and analysis of immune cells, flow cytometry, western
blotting, ELISA, and epitope mapping. The project will be
tailored to best match the student’s interests and training
background. Interested students should contact
Chrissie Collins, chrissie.collins@burnet.edu.au
Understanding Malaria Transmission and

Immunity to inform Malaria Elimination
Immunity to SARS-CoV-2 in Brazil
Malaria transmission in populations involves interactions
Supervisors: Professor James Beeson and
between infection rates and prevalence that drive transmission,
Professor Heidi Drummer
and the presence of malaria immunity that has the potential
to reduce transmission. Malaria immunity can act to reduce Continuing epidemic waves of COVID-19 are anticipated
infection rates and levels of malaria parasitemia, and specific in many countries because of emerging viral variants, the
components of immunity can also function to directly block moderate efficacy of vaccines being implemented in many
transmission of malaria. This is known as transmission-blocking countries, waning immunity and substantial vaccination
immunity. hesitance. Brazil has undergone one of the worst SARS-
CoV-2 global epidemics and vaccines are now being
Currently, very little is known about the interactions between
implemented.
malaria infection rates and patterns and malaria immunity
in populations, and how these interact. Malaria control Longevity of antibody-mediated immunity and memory
programs face the challenge that as malaria transmission responses induced by previous infection and vaccines are
declines, malaria immunity also declines, which places likely to vary and to be boosted with SARS-CoV-2 exposure
the population at higher risk of malaria transmission and and additional vaccine doses. Epitopes targeted by immunity
rebound epidemics. and the breadth of antibody responses associated with long-
lasting immunity are still unclear, particularly in the setting
This project will investigate the impact of malaria immunity
of a mixture of natural- and vaccine-induced immunity. This
on malaria infection rates and transmission of malaria in
project will focus on two key knowledge gaps that determine
populations. The student will analyse various parameters
the risk of ongoing transmission and epidemics: i) declining
to define the patterns of infection and immunity, with a
immunity over time and ii) the emergence of new variants
particular focus on defining the interaction between immunity
that escape vaccine-induced or naturally-acquired immunity.
and malaria transmission.
As part of an international collaborative program, the project
The findings of this project will be highly relevant to will investigate immunity in cohorts of naturally infected
informing malaria elimination efforts and understanding the and vaccinated individuals and will use a comprehensive
value of incorporating vaccines into elimination strategies. range of immunoassays including quantification of antibody
Skills acquired may include established high-throughput magnitude (subclasses and isotypes), neutralizing antibodies
immunoassays and assays that quantify the functional to different variants, avidity and antibody-dependent cellular
activity of immune responses (e.g. flow cytometry, cytotoxicity. Additionally, studies will profile specific epitopes
Fc-receptor mediated immunity, complement activation, targeted by immunity and their relationship to immune
western blots, ELISA, neutralisation assays). This could be escape by virus variants.
expanded to include modelling of the interaction between
The overall objective of this work is informing optimal
infection and immunity, and how this may impact on malaria
vaccination policy, regimens, and refinements by
elimination and control. Interested students should contact
understanding key gaps in natural and vaccine induced
Chrissie Collins, chrissie.collins@burnet.edu.au Immunity to
immunity.

Burnet Institute
Professor Gilda Tachedjian

EMAIL gilda.tachedjian@burnet.edu.au
UP TO THREE VACANCIES
TELEPHONE +61 3 9282 2256
Retroviral Biology and Antivirals Laboratory (RBA) (Tachedjian Lab), Life Sciences Discipline
OFFICE
Disease Elimination and Health Security Programs, Burnet Institute
WEB www.burnet.edu.au/working_groups/21_tachedjian_laboratory
Top: Lactobacilli attached to a vaginal epithelial

cell. Bottom: Cell infected with HIV (green dots).
Right: An Australian black flying fox (Pteropus
alecto).
Bat Antiviral Defenses Against Viruses

Professor Gilda Tachedjian, Dr Joshua Hayward and
Dr Paula Ellenberg
are present as a critical part of eukaryotic genomes,
Bats are a major reservoir of viruses such as Hendra virus, also indicates that bats have a long history of infection
Ebola virus, and coronaviruses that are pathogenic in with gammaretroviruses and betaretroviruses indicating
humans but not in bats. The reason why bats can coexist that retroviruses have circulated in bats throughout their
with these viral pathogens is unknown. However, one evolutionary history. How the innate immune system of bats
explanation is that the coevolution of bats and their viruses has adapted to tolerate or combat infection with retroviruses
has resulted in a ‘peace treaty’, a biological equilibrium in remains largely unexplored, and this project seeks to further
which viral replication is regulated in such a way that both characterise the interactions between bat restriction factors
host and virus can co-exist without undue antagonism. The and the Hervey pteropid gammaretrovirus (HPG), the first
role of the host’s immune system is to control infections extant retrovirus discovered in bats Hayward, Tachedjian
and antiviral restriction factors are at the front line of the et al. 2020 PNAS 117(17). This is a joint project between
innate immune response that targets viruses. These the Tachedjian Lab and CSIRO Australian Animal Health
antiviral restriction factors were originally discovered to Laboratory.
restrict retroviruses from other mammalian species, such
as HIV (Hayward et al 2018 Mol Biol Evol 35(7)), and some
of these factors e.g. tetherin, can additionally restrict
paramyxoviruses, coronaviruses and filoviruses. Bats
have recently been found to be an important reservoir
of retroviruses from the genus Gammaretrovirus and are
involved in transmission of retroviruses between mammalian
species (Hayward et al 2020 PNAS 117(17)). The genomic
fossil record of endogenous retroviral seequences, which

Vaginal Microbiota and HIV Susceptibility Discovery of a New Drug Class for HIV
Professor Gilda Tachedjian, Dr Anna Hearps, Dr Treatment and Prevention
Lindi Masson, Dr Paula Ellenberg and Dr Joshua Professor Gilda Tachedjian, Dr Paula Ellenberg
Hayward and Dr David Chalmers
The composition of the vaginal microbiota can influence There is a real threat that drug resistance, toxicity and
the transmission of pathogens such as HIV. Women intolerance will eventually lead to exhaustion of antiretroviral
colonised with optimal vaginal bacterial communities, drug options for both HIV treatment and prevention,
typically dominated by beneficial Lactobacillus spp., have a especially since there is little in the way of new drug
decreased risk of acquiring and transmitting HIV compared classes in the pipeline. We have initiated a drug discovery
to women colonised with non-optimal microbiota. A non- program targeting HIV-1 reverse transcriptase (RT) to
optimal vaginal microbiota is characterised by a depletion of identify compounds that inhibit this essential enzyme. We
beneficial Lactobacillus spp. and high relative abundance of are using an innovative and validated paradigm for drug
non-beneficial bacterial species, as exemplified by bacterial discovery called fragment-based drug design (FBDD) that
vaginosis (BV), which is a common form of vaginal dysbiosis uses very small compounds called ‘fragments’ to find
in women of reproductive age that occurs in up to 55% inhibitors with novel mechanisms of action against HIV-1 RT.
of women in sub-Saharan Africa where HIV predominates Using FBDD means screening far fewer compounds than
(McKinnon et al 2019 AIDS Res Hum Retroviruses 25(3)). conventional drug screens since fragments are so small,
Non-optimal vaginal microbiota increase local pro- and can be developed into more potent drugs. Two screens
inflammatory cytokines, recruit activated HIV target cells and have identified promising fragments that inhibit HIV-1 RT.
disrupt cervicovaginal epithelial barrier integrity that together We have discovered fragments with mechanisms that are
drive increased risk of HIV acquisition. While studies have distinct from other drugs that inhibit HIV-1 RT in the clinic
described the association between the vaginal microbiota (La et al 2015 PNAS 112:6979) and some of these have
and increased susceptibility to HIV and sexually transmitted been progressed to molecules that have low micromolar
infections (STIs), relatively little is known about how the activity against wild-type and drug-resistant RT. The aim of
microbiota and its metabolites act on the epithelium to this study is to progress fragment hits into more potent RT
mediate this effect. inhibitors or drug leads. Compounds that are structurally
Major distinguishing features of women colonised with related to the fragment hit will be evaluated for their ability to
optimal vaginal microbiota compared to women with BV is bind and inhibit wild-type and drug-resistant RT, as well as
a dramatic increase in the levels of lactic acid and depletion inhibit HIV-1 replication. This study will identify leads for the
of short chain fatty acids (SCFAs) suggesting a role for development of a novel class of RT inhibitor for use in HIV
these metabolites as effector molecules of vaginal bacteria. treatment and prevention.
Projects are available to determine the direct anti-HIV This is a joint project between the Tachedjian Lab and
mechanism of vaginal microbiota metabolites, their immune Monash Institute of Pharmaceutical Sciences.
modulatory and barrier promoting effects on cervicovaginal
epithelial cells, and to examine the roles of key members of
the vaginal bacterial community (Delgado-Diaz et al 2020
Front Cell Infect Microbiol 9:446; Chetwin et al 2019 Sci Rep
9(1917)). These studies are underpinning an exciting program
at the Burnet to advance strategies to treat and prevent
genital inflammation and consequently susceptibility to HIV,
other STIs as well adverse reproductive health outcomes.

Victorian Infectious Diseases Reference Laboratory,
Peter Doherty Institute for Infection and Immunity.
Professor Peter Revill

EMAIL peter.revill@mh.org.au
ONE VACANCY
TELEPHONE +61 3 9342 9604
Research and Molecular Development (Revill lab) VIDRL

OFFICE
Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Melbourne VIC 3000
Revill group The hepatitis B life cycle
Determining the importance of conserved

residues identified throughout the HBV
genome on viral replication and their
potential as new therapeutic targets.
Professor Peter Revill and , Dr Margaret Littlejohn
and Ms Vitina Sozzi
We have identified a number of residues throughout the HBV
genome that are 100% conserved across all major HBV
genotypes and phases of chronic HBV disease. This project
will investigate which of these conserved sequences are most
important for HBV replication and thus represent potential
antiviral targets, using a range of in vitro and in vivo models.
Techniques to be utilised include cell culture; HBV transfection
and infection, DNA and RNA purification; northern, Southern
and western blotting; quantitative serology; siRNA or CRISPR
knockdown; PCR, droplet digital PCR and sequencing.

Institute of Vector-borne Disease
Dr. Johanna Fraser

EMAIL johanna.fraser@monash.edu
TWO VACANCIES
TELEPHONE + 61 3 9902 0129
OFFICE Institute of Vector-borne Disease (IVBD), 12 Innovation Walk
WEB https://www.monash.edu/ivbd, https://www.worldmosquitoprogram.org/
When Wolbachia strains (e.g. wMel, red) are

artificially introduced into Ae. aegypti (the major
vector of human viruses such as dengue), it
resides in tissues including the salivary glands
Dr. Johanna Fraser Dr. Heather Flores Dr. Kat Edenborough (sg) and prevents transmission of infectious virus.
Defining the mechanisms of Viral resistance towards Wolbachia

Wolbachia-mediated virus inhibition Dr. Kat Edenborough and Dr. Johanna Fraser
Dr. Johanna Fraser and Dr. Heather Flores As this Wolbachia biocontrol system ages in the field, there
Wolbachia is an endosymbiotic bacterium found in nearly comes an increased risk of viral resistance developing towards
60% of insect species. It is not naturally found in Aedes Wolbachia. We have established a novel in vivo viral passaging
aegypti, the mosquito vector responsible for transmitting technique in mosquitoes to study how virus populations evolve
significant human pathogenic viruses such as dengue and towards Wolbachia. This project aims to characterize the
Zika. Work over the last decade has shown that Wolbachia ability of Wolbachia-adapted viral mutants to infect mosquito
can be introduced into Ae. aegypti, and interestingly, it and human hosts by using molecular and classical virology
can impart a potent antiviral state in these mosquitoes. An methods.
overwhelming body of evidence has now demonstrated
the efficacy of Wolbachia as a biocontrol tool, including
significantly reducing dengue disease in regions where these
mosquitoes are established in the field. However, the detailed
mechanisms by which virus inhibition occurs are yet to be
fully elucidated. This project will utilize a range of molecular
techniques to examine hypotheses such as nutritional
parasitism and host cell organelle disruption that may
contribute to the antiviral impacts of Wolbachia. The project
will make use of a unique set of Wolbachia-transinfected
mosquito lines developed in-house and will be conducted in
the lab alongside the World Mosquito Program - the pioneers
and world-leading drivers of Wolbachia-based technologies.

Notes

Notes

Further information
Professor John Boyce
Honours Coordinator
Department of Microbiology
School of Biomedical Sciences
Room 215
19 Innovation Walk
Clayton Campus
Monash University, VIC 3800
Telephone: +61 3 9902 9179
Email: john.boyce@monash.edu
Monash Biomedicine Discovery Institute

23 Innovation Walk
Monash University
Wellington Road
Clayton, Victoria, 3800
Telephone: +61 3 9902 9400
Email: bdi-enquiries@monash.edu
www.med.monash.edu
facebook.com/MonashBD
@MonashBDI
Monash University reserves the right to alter information, procedures, fees and regulations contained in this document.
Please check the Monash University website for updates (monash.edu). All information reflects prescriptions, policy and
monash.edu/discovery-institute
practice in force at time of publication. Revised by Monash Print 364773. CRICOS Provider: Monash University 00008C.
Published September 2023.

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Department of Microbiology

2023 Honours Programs

The Honours programs for both Bachelor of Biomedical Supervisor Interviews

B. Sc (Hons): November 11, 2022 Microbiology Coursework

i A statistics module, with accompanying MCQ test and

i A written critique of a scientiﬁc paper, in a three-hour

2023 Microbiology Honours Projects | 1

Additional requirements BSc Graduates of Other Universities

Part-time study and mid-year entry

Statistics Module 7.5%

Common written component 7.5%

2 | 2023 Microbiology Honours Projects

2023 Microbiology Honours Projects | 3

OFFICE Room 215, 19 Innovation Walk (Building 76)

Characterising the role of small RNAs in Defining the Mechanisms of Pasteurella

4 | 2023 Microbiology Honours Projects

OFFICE Room 380, 15 Innovation Walk (Building 75)

Professor Mariapia Degli-Esposti Dr Iona Schuster Dr Christopher Andoniou

MCMV, Immunity and Ageing Viral Infection and Autoimmunity

2023 Microbiology Honours Projects | 5

OFFICE Room 136, 19 Innovation Walk (Building 76)

Professor Chris Greening Dr Rachael Lappan Dr Tom Watts

6 | 2023 Microbiology Honours Projects

2023 Microbiology Honours Projects | 7

OFFICE Room 133, 19 Innovation Walk (Building 76)

The crystal structure of the outer-membrane protein BonA

8 | 2023 Microbiology Honours Projects

2023 Microbiology Honours Projects | 9

OFFICE Room 231, level 2, 19 Innovation Walk (Building 76)

2023 Microbiology Honours Projects | 11

OFFICE Room 220, 19 Innovation Walk (Building 76)

Professor Jian Li Dr Sue C. Nang Dr Yan Zhu Dr Jinxin Zhao

Laboratory of Antimicrobial Systems Deciphering the Mechanisms of

12 | 2023 Microbiology Honours Projects

As the optimal phage-antibiotic combination and dosage

2023 Microbiology Honours Projects | 13

OFFICE Room 233; Room 252, 19 Innovation Walk

14 | 2023 Microbiology Honours Projects

2023 Microbiology Honours Projects | 15

OFFICE Room 152, 19 Innovation Walk (Building 76)

Understanding the Host Repair Response Anti-sporulation strategies targeting

16 | 2023 Microbiology Honours Projects

2023 Microbiology Honours Projects | 17

OFFICE Room 137, 19 Innovation Walk (Building 76)

A/Professor Sheena McGowan Dr Chaille Webb Dr Chathura Suraweera

The McGowan laboratory is interested in characterising Development of Phage Lysins

18 | 2023 Microbiology Honours Projects

2023 Microbiology Honours Projects | 19

OFFICE Room 136, 19 Innovation Walk (Building 76)

A/Professor Greg Moseley

20 | 2023 Microbiology Honours Projects

2023 Microbiology Honours Projects | 21

OFFICE Room 153, 19 Innovation Walk (Building 76)

Coxiella (red) replicates in a

22 | 2023 Microbiology Honours Projects

OFFICE Room 153, 19 Innovation Walk (Building 76)

MECHANISMS OF PATHOGENESIS OF Project 1

24 | 2023 Microbiology Honours Projects

Note: Working with animals is not compulsory for any of the

2023 Microbiology Honours Projects | 25

OFFICE Room 149, 19 Innovation Walk (Building 76)

Functional genomics to understand Characterisation of novel iron regulators in K.