2021 Honours Programs in Microbiology - Department of Microbiology - Monash University
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Department of Microbiology
2021 Honours Programs
in Microbiology
2021 Honours Coordinator Deputy Coordinator
Associate Professor John Boyce Professor Julian Rood
Room: 215, 19 Innovation Walk Room: 155, 19 Innovation Walk
Phone: +61 3 9902 9179 Phone: +61 3 9902 9157
Email: john.boyce@monash.edu Email: Julian.Rood@monash.edu
monash.edu/discovery-institute
2021 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
The objectives of these courses are to develop the laboratory with potential supervisors at any suitable time, by
skills required for research in microbiology and the ability appointment. Following these discussions, students
to critically evaluate microbiological research. Students will need to give Associate Professor John Boyce
also achieve a detailed understanding of specialised topics their Microbiology application forms:
in microbiology and enhance their communication skills in www.monash.edu/discovery-institute/honours/so-how-do-i-apply
written and oral presentations. indicating their project preferences, and any additional
documentation required. You do not need to wait until
The Department looks forward to welcoming you in 2021. November 13th to hand in your preference forms, the
We feel that our friendly, constructive and highly productive earlier the better.
working environment provides an excellent opportunity for
honours students to develop an understanding of the research
process and to achieve their full research potential. Projects Outside the Department
It is possible for students to complete their coursework within
Formal Application Process the Department of Microbiology at Clayton, and their research
project off-campus. Under these circumstances, students
Application for Microbiology Honours entry involves must travel between locations when required. The thesis
a two part application process. examination takes place at the same time for all students
1. Formal application to the relevant faculty by enrolled through Microbiology.
B. Sc (Hons): November 13, 2020
www.monash.edu/science/current-students/ Microbiology Coursework
science-honours The coursework conducted within the Department of
B. Biomed. Sci (Hons): November 13, 2020 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 Associate Professor one colloquium. Each colloquium is held during a one month
John Boyce (no later than November 13, 2020). 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 2021 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, an accompanying workshop and test
2021 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 least
students who have problems with English expression so this
70% in 24 points of relevant level-three science units. This
can be addressed by directed English writing instruction. It
generally includes at least 18 points of Microbiology units.
also, of course, compels the students to become thoroughly
Students studying combined Science degrees must be eligible
conversant with their area of research.
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 22, 2021 (mid year
BSc and distinction grades in Microbiology or closely related
begins July 19) with a series of introductory lectures, before
subjects. A certified copy of the applicant’s academic record
the students start work on their research projects. These
and a statement to the effect that they have qualified for
lectures contain information on the course, departmental
a pass degree are required as soon as they are available.
facilities and laboratory safety. In the second half of the year
students may be given specific training in the presentation Monash BBiomedSci students
of written reports, and in oral presentation of their work. It
Students must have completed all requirements for the award
is compulsory for students to attend the introductory lecture
of the pass degree of Bachelor of Biomedical Science offered
course, all departmental seminars, and any short courses
at Monash University. They must also have an average
on written and oral presentations.
of 70% or higher in at least 24 points at third year level, with
12 points from third year core units.
Assessment
BBiomedSci graduates from other universities
Final assessment of the BSc Honours program
Students applying for admission based on a qualification other
follows the format:
than the pass degree of Bachelor of Biomedical Science offered
Literature survey 7.5% at Monash University will need to demonstrate that they have
achieved an appropriate standard in studies comparable to 24
Research report/report review 60% points of BBiomedSci subjects as stipulated above.
Seminar 7.5%
Part-time study and mid-year entry
Microbiology coursework 25%
The department prefers students to study on a full-time basis.
However, it may be possible under special circumstance to
Final assessment of the BBiomedSci Honours program
complete the Honours degree in two consecutive years by
follows the format:
doing the coursework and research project in separate years.
Literature survey 7.5% It may also be possible to start the course mid-year. In both
of these circumstances, the arrangements are made on an
Research report/report review 60% individual basis between applicants and supervisors.
Seminar 7.5%
Microbiology coursework 10%
Statistics Module 7.5%
Common written component 7.5%
2 | 2021 Microbiology Honours Projects
Research Projects
2021
2021 Microbiology Honours Projects | 3
Associate Professor John Boyce
EMAIL john.boyce@monash.edu
ONE VACANCY
TELEPHONE +61 3 9902 9179
OFFICE Room 215, 19 Innovation Walk (Building 76)
WEB https://www.monash.edu/discovery-institute/boyce-lab
Associate Professor John Boyce Dr Marina Harper Macrophages infected with Burkholderia
Characterisation of the Acinetobacter Defining the Mechanisms of Pasteurella
baumannii Type VI Secretion System multocida Pathogenesis and Identifying
Dr. Marina Harper and A/Professor John Boyce Novel Virulence Regulators
Acinetobacter baumannii has been identified as one of the Dr. Marina Harper, Dr. Marianne Megroz,
top three dangerous Gram-negative hospital pathogens as Mr Thomas Smallman and A/Professor John Boyce
it can cause a range of life-threatening infections and most Pasteurella multocida is a Gram-negative bacterial pathogen
strains are now resistant to the majority of current antibiotics. that causes a range of diseases in humans, cattle, pigs and
We have characterised a type VI secretion system (T6SS) poultry. The animal diseases result in serious economic losses
in A. baumannii that delivers antibacterial toxic proteins into worldwide in food production industries. We are interested in
other bacteria to give the cell a competitive advantage. understanding the molecular mechanisms of pathogenesis in
We are interested in defining the full complement of toxic this bacterium with an aim to developing new, more effective
effector proteins, determining how they kill other bacteria and widely applicable vaccines or antimicrobial drugs.
and characterising how the T6SS delivers these toxic proteins Recent work in our lab, using comparative genomics and
to the correct compartment of key competitor strains. transposon insertion site mutagenesis, has comprehensively
This project will use a mix of PCR, directed mutagenesis, defined the P. multocida genes essential for a range of virulence
complementation, heterologous protein expression and phenotypes, including growth in serum and production of
protein-protein interaction approaches to identify novel toxin the anti-phagocytic bacterial capsule. With this crucial data
functions and identify crucial T6SS delivery determinants. as a base, in this project we will use directed mutagenesis,
A complete understanding of the A. baumannii T6SS, including complementation, whole-genome transcriptomic and proteomic
the function of novel toxins and how these toxins are selected techniques and established in vitro and in vivo assays to define
for targeted delivery, will allow us to genetically engineer the molecular mechanisms by which this important pathogen
commensal bacterial strains as live antibacterial delivery avoids killing by the host immune system and causes disease.
systems for the control of other multi-drug resistant pathogens.
4 | 2021 Microbiology Honours Projects
Professor Mariapia Degli-Esposti
EMAIL mariapia.degli-esposti@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9905 6162
OFFICE Room 380, 15 Innovation Walk (Building 75)
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 viral how these correlate with the onset of autoreactive responses. We
infections impact and shape the aging immune system is not have shown that a strong anti-viral T cell response generated in
well understood. In this regard, we are particularly interested the absence of certain immune regulatory mechanisms improves
in cytomegalovirus (CMV), a virus that is never fully cleared viral control. However, once the virus is controlled, this strong
and remains with its host life-long. CMV infection causes the anti-viral response leads to increased generation of auto-specific
gradual expansion of certain CD8+ T cell memory populations, immune responses resulting in a loss of tissue function. The
a phenomenon that has been linked with both limiting and autoimmune disease generated represents the best available
enhancing immune responses to other challenges. Using model of the second most common autoimmune disease of
the well-established mouse model of murine CMV (MCMV) man, Sjogren’s Syndrome, a condition that affects overall health
infection we aim to examine the impact of this in immune by severely compromising exocrine gland function. Experimental
compartments during ageing. Approaches will include high- approaches will include in vitro and in vivo techniques using
parameter multicolour flow cytometric analysis of immune wildtype as well as gene-targeted mouse strains. Techniques
cell subsets as well as bulk and single cell assays of immune include the preparation of different tissues for histological analysis
functionality. The ultimate aim is to gain a better understanding of tissue pathology, characterization of infiltrating cell types, and
of how CMV infection shapes the immune system over time assessment of changes in tissue architecture. Furthermore,
and how this affects the aging immune system. we use flow cytometry to characterize and quantify immune
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.
2021 Microbiology Honours Projects | 5
6 | 2021 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 secretion
Helicobacter pylori Causes Stomach Cancer and H. pylori-host interactions. We aim to understand the
Helicobacter pylori is a Gram-negative gastric bacterium that molecular basis of how H. pylori induces stomach cancer, with
has co-evolved with humans for more than 50,000 years. It the ultimate goal of providing knowledge for a better treatment
colonises the stomach of over 50% of the world’s population, and/or prevention of H. pylori-associated stomach diseases.
making it one of the most prevalent human pathogens. It is a Projects are available to address the following key questions:
causative agent of severe gastric diseases including chronic i How does H. pylori trigger inflammation and carcinogenesis
gastritis, peptic ulcer and stomach cancer. H. pylori has been through the virulence functions of CagL and CagA?
classified as a Group I (high-risk) carcinogen.
i Can cagL and cagA genotypes predict gastric cancer risk
Highly virulent strains of H. pylori harbour a type IV secretion and therefore help pinpoint cancer-prone patients for early
system (T4SS), a secretion machinery that functions as a treatment?
“syringe” for injecting virulence proteins and peptidoglycan i How do CagL function as a host-activated sensor during
into the host cell. We discovered that CagL, a specialised type IV secretion?
adhesin present on the surface of the H. pylori T4SS, binds to
i How do CagL and CagA modulate host cell signalling
the human integrin α5β1 receptor on stomach lining cells.This
during chronic H. pylori infection?
binding activates the T4SS and hence the secretion of virulence
i Can we utilise the type IV secretion system of H. pylori
factors including the highly immunogenic and oncogenic protein,
for delivery of therapeutic proteins?
CagA, into stomach cells. ‘Injected’ CagA then interacts with
host signalling molecules and triggers activation of a suite The available honours projects will enable one to gain
of host responses. Interestingly, our recent findings suggest experience with the important techniques of molecular
that CagL can also directly modulate host cell functions. The cloning and mutagenesis, bacterial culture, eukaryotic cell
precise mechanisms by which CagL functions both as a culture techniques, mouse infection models, CRISPR, RNAi,
host-activated sensor of the H. pylori T4SS and as a direct immunostaining, Western blotting, ELISA, confocal laser
activator of aberrant host responses remain to be fully scanning microscopy, live cell imaging, etc. Someone who is
understood. enthusiastic in learning about the exciting secrets of bacteria-
host interactions, infectious cancer biology and bacterial
pathogenesis is strongly encouraged to apply.
2021 Microbiology Honours Projects | 7
Professor Jian Li
EMAIL jian.li@monash.edu
THREE VACANCIES
TELEPHONE +61 3 9903 9702
OFFICE Room 220, 19 Innovation Walk (Building 76)
WEB https://research.monash.edu/en/persons/jian-li
Professor Jian Li Dr Mohammad Azad Dr Yan Zhu Dr Sue C. Nang
Laboratory of Antimicrobial Systems Deciphering the Mechanisms of
Pharmacology Polymyxin Resistance in P. aeruginosa
My lab focuses on antimicrobial discovery and Using Computational Biology
pharmacology against Gram-negative ‘superbugs’ Professor Jian Li and Dr Yan Zhu
(namely Pseudomonas aeruginosa, Acinetobacter baumannii,
P. aeruginosa is a critical threat to human health worldwide.
and Klebsiella pneumoniae). There has been a marked
Polymyxins are a group of last-line antibiotics against Gram-
decrease in the discovery of novel antibiotics over the last
negative ‘superbugs’, including MDR P. aeruginosa.
two decades. As no novel class of antibiotics will be available
against Gram-negative ‘superbugs’ in the near future, it We are integrating genomics, transcriptomics, proteomics,
is crucial to optimise the clinical use of ‘old’ polymyxins metabolomics, and lipidomics to systematically examine
using systems pharmacology and to develop novel, safer bacterial responses to polymyxins and their combinations.
polymyxins and innovative therapeutics.
This project aims to:
My major research programs include:
(1) construct a genome-scale model of metabolism and gene
(1) optimising clinical use of polymyxins and their combinations expression (ME model) for P. aeruginosa using literature and
using pharmacokinetics/pharmacodynamics/toxicodynamics our multi-omics data;
(PK/PD/TD) and systems pharmacology;
(2) use the constructed ME model to simulate cellular
(2) elucidation of mechanisms of antibacterial activity, resistance, responses to polymyxins; and
and toxicity of polymyxins; and
(3) predict key genes and pathways contributing to polymyxin
(3) discovery of novel, safer polymyxins and innovative resistance and validate their functions with our comprehensive
therapeutics against multidrug-resistant (MDR) Gram- mutant library.
negative bacteria.
This multidisciplinary project will, for the first time,
My lab is funded by the US National Institutes of Health (NIH) characterise the complex interplay of signaling, regulation
and Australian NHMRC. and metabolic pathways involved in polymyxin resistance,
thereby optimising polymyxin chemotherapy in patients.
8 | 2021 Microbiology Honours ProjectsPhage-Antibiotic Therapy Pulmonary Toxicity of Novel Polymyxin
in the Postantibiotic Era Combination Therapies
Prof Jian Li and Dr Sue C. Nang Dr Mohammad Azad and Professor Jian Li
Antimicrobial resistance has become one of the greatest Current dosing recommendations of parenteral polymyxins
global threats to human health and pandrug-resistant (PDR) are suboptimal for treatment of respiratory tract infections
Klebsiella pneumoniae has been identified by the WHO as due to poor drug exposure at the infection site. Moreover,
one of the 3 top-priority pathogens urgently requiring novel nephrotoxicity is the dose-limiting factor and can occur in
therapeutics. These ‘superbugs’ cause life-threatening up to 60% of patients. Pulmonary delivery of polymyxins
infections, particularly in the critically ill, and polymyxins as monotherapy and in combination with other antibiotics
are often used as the last option. Worryingly, increasing has offered a great promise for bacterial eradication in the
emergence of polymyxin resistance highlights the urgency respiratory tract. However, we have shown that polymyxins
to develop novel therapeutics to treat PDR K. pneumoniae. localise in mitochondria of human lung epithelial cells and
Bacteriophage (i.e. phage) have recently attracted substantial activate multiple apoptotic pathways. This multi-disciplinary
attention as a potential alternative against PDR bacterial project aims to investigate the effect of polymyxins and their
infections; however, resistance to phage therapy (including synergistic combinations with other key classes of antibiotics on
cocktails) in K. pneumoniae can rapidly develop. Fortunately, human lung epithelial cells, using fluorescence activated cell
phage resistance may restore bacterial susceptibility to certain sorting (FACS), metabolomics, proteomics, transcriptomics
antibiotics and therefore, optimal phage-antibiotic combination and cutting-edge imaging techniques. This project will provide
therapy provides a superior approach to fight against these the much-needed pharmacological information for safer and
superbugs. Contemporary antimicrobial pharmacology plays more efficacious use of polymyxin inhalation therapy against
a critical role in optimizing antibiotic dosage regimens, but life-threatening lung infections.
lacks systems and mechanistic information. Importantly,
antibiotic dosing strategies cannot be easily extrapolated
into phage therapy, mainly due to the complex disposition,
host specificity and self-replication of phages. As the optimal
phage-antibiotic combination and dosage regimens also
depend on the dynamics of infection and host responses,
innovative strategies incorporating systems pharmacology
and host-pathogen-phage-antibiotic interactions have
a significant potential in optimising phage-antibiotic
combinations. This project will employ cutting-edge systems
pharmacology to generate urgently needed information for
rationally optimising novel phage-antibiotic combinations in
patients.
2021 Microbiology Honours Projects | 9Professor 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
Professor Trevor Lithgow Dr Rhys Dunstan Dr Christopher Stubenrauch
Mapping Diversity of Bacteriophage This project aims to assess phage diversity through a classical
environmental microbiology approach: using water samples
with Genomics and Structural Biology collected from diverse locations around the world, the phages
Dr Rhys Dunstan and Professor Trevor Lithgow therein will be concentrated and plated on a lawn of bacteria.
Bacteriophages (phages) dominate numerous ecosystems, Attention will be focused on phages that infect the pathogen
and are most often isolated from water sources. Recently, Klebsiella pneumoniae or a closely related plant commensal
phage discovery has been accelerated using new generation Klebsiella pseudopneumoniae that looks set to emerge as an
sequencing strategies: (i) viral metagenomics, in which complex important pathogen. Using a combination of electron microscopy
phage populations are harvested en masse from environmental to assess virion morphology, and bioinformatics for comparative
sources, and (ii) data mining archives of bacterial genome genomics and protein identification, the project would
sequence information, to detect embedded prophage and classify, catalogue and compare the various phage isolated.
phage-related sequences. As powerful as they are, these Finally, a systematic assessment of cocktails of the various
bioinformatics-based approaches do not yield virions for phage will be undertaken to determine killing efficacy for
wet-lab analyses. Understanding the diversity present in future therapeutic work.
the architecture and the biology of phages requires isolating
and characterizing active virions.
10 | 2021 Microbiology Honours ProjectsUnderstanding how bacteria piece While the importance of αβ-barrel proteins in AMR and
together αβ-barrel proteins disease is widely appreciated, their mechanisms of assembly
are not. This project aims to determine which folding factors
Dr Christopher Stubenrauch and Professor Trevor
assist in the assembly of αβ-barrel proteins that lead bacteria
Lithgow
to becoming such successful pathogens and involves
Within crowded biological systems, like a bacterial cell, the use of a range of general molecular microbiological
folding factors are essential for ensuring correct protein techniques, MIC analyses, western immunoblotting, and
assembly on a biologically relevant time scale. Traditionally, 3 pulse chase assembly assays.
classes of outer membrane proteins have been recognised
that each follow distinct and well-characterised assembly
pathways: β-barrel proteins, lipoproteins, and secretins.
While the majority of proteins fall clearly within the confines of
these three protein groups, a complex protein class referred
to as αβ-barrel proteins does not.
Members of the αβ-barrel protein family can readily be
found in most Gram-negative bacteria and are one of the
most important virulence factors that promote antimicrobial
resistance (AMR) and bacterial pathogenesis. The model
bacterium we study, Escherichia coli, houses up to 6
different αβ-barrel proteins, including the protein TolC – the
promiscuous outer membrane component of a range of
antimicrobial efflux pumps and type 1 secretion systems.
2021 Microbiology Honours Projects | 11Professor Dena Lyras
EMAIL dena.lyras@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9902 9155
OFFICE Room 152, 19 Innovation Walk (Building 76)
Professor Dena Lyras Dr Yogitha Srikhanta Dr Steven Mileto Dr Milena Awad A/Professor Priscilla Johanesen
Understanding the Host Repair Response Anti-sporulation strategies targeting
to Clostridioides difficile Infection spore-forming pathogens
Professor Dena Lyras and Dr Steven Mileto Professor Dena Lyras and Dr Yogitha Srikhanta
Gastrointestinal infections often induce epithelial damage Spore-forming bacteria include the devastating human and
that must be repaired for optimal gut function. While animal pathogen Clostridioides difficile, the food spoilage
intestinal stem cells are critical for this regeneration process, pathogen Bacillus cereus and the agent for bioterrorism
how they are impacted by enteric infections remains poorly Bacillus anthracis. Spores are the infectious particles of
defined. We recently investigated infection-mediated these pathogens and their resistant and unique structure
damage to the colonic stem cell compartment and how makes them difficult to eradicate. Their persistence
this affects epithelial repair and recovery from infection, properties enable the spread of disease, resulting in
using the pathogen Clostridioides difficile, which induces a fatalities and economic devastation in environments such
spectrum of diarrheal diseases mediated by two exotoxins, as health care settings, the food industry and public
TcdA and TcdB. These toxins share sequence and spaces in the case of weaponised anthrax. Despite these
structural homology but may contribute to disease severity major problems, there are no strategies to prevent spore
unequally. We have shown that infection disrupts mouse production. C. difficile is of considerable medical interest
intestinal cellular organisation and integrity deep into the due to the high disease burden and global challenge of
epithelium, and exposes the otherwise protected stem cell managing the consequences of infection. C. difficile spores
compartment. This disruption of the gut epithelium occurs are highly resistant to antibiotic treatment and disinfectants
primarily through TcdB-mediated damage and altered stem and are responsible for facilitating disease transmission
cell signalling and function, resulting in a significant delay and recurrent infection. Our published work has shown
in recovery and repair of the intestinal epithelium. However, that cephamycins, a group of beta-lactam antibiotics, can
the mechanisms of stem cell intoxication, and the effects inhibit spore formation of C. difficile epidemic isolates by
of different TcdB variants on stem cell function, remain blocking the activity of spore-specific penicillin binding
unknown. Animal models of infection will be used, together proteins. Of clinical relevance, co-treatment of mice with the
with specific C. difficile mutants and strain variants, to cephamycins and the standard-of-care C. difficile treatment
study virulence factors and host interactions, allowing us vancomycin, which is ineffective against spores, prevented
to gain a mechanistic understanding of how these bacteria recurrent infection. This project will extend our C. difficile
interact with, and damage, the host gut. We will also use spore formation inhibition studies to other spore-forming
various tissue culture systems to examine the specific bacteria, including both pathogens and commensals, to
molecular mechanisms that lead to TcdB-mediated stem work towards better drug delivery strategies for treatment
cell dysfunction, including stem cell-derived organoids. of diseases caused by these pathogens.
12 | 2021 Microbiology Honours ProjectsInterrogating 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 and
A/Professor Priscilla Johanesen
The human and financial cost of Clostridioides difficile global
epidemics is substantial and alarming, with C. difficile listed The treatment of bacterial infections in animals and humans
as the number one antibiotic-resistant bacterial threat in the has relied on the use of antibiotics for over 50 years.
USA. A key driver of C. difficile infection relates to the ability However, one consequence of the use of these drugs is
of this bacterium to form spores, an inert and highly robust antibiotic resistance, which is now one of our most serious
cell type, which allows survival of the bacterium in hostile global health threats. Bacteria can become resistant to
environments. Spores initiate and transmit disease, and antibiotics through the lateral transfer of resistance genes,
contribute to disease relapse, whereas the vegetative cell form which are often located on mobile genetic elements such
of C. difficile colonises the gut and produces potent toxins as plasmids and transposons. This project will focus on a
that cause disease. We have found that the host protease mechanism of lateral gene transfer known as conjugation,
plasminogen migrates to the gut following toxin mediated which involves direct cell-to-cell contact and transfer of
damage and that C. difficile spores, but not vegetative cells, genetic material through bacterial structures known as
recruit plasminogen to their surface. Importantly, we have also conjugative pili. Apart from the conjugative pili, very little is
shown that the active form of plasminogen (plasmin) modifies known about the role that other bacterial surface structures
the spore surface, increasing the germination rate and leading play in conjugation. Here, we will examine the role of
to a faster production of toxin producing cells that culminates numerous bacterial structures in DNA transfer efficiency
in disease exacerbation. In this project, we will further using molecular techniques, which may identify new
interrogate the effects of this alteration to the spore surface therapeutic targets and strategies through which the spread
using cutting-edge imaging technologies such as STimulated of antibiotic resistance can be inhibited.
Emission Depletion (STED) microscopy and immuno-electron
microscopy, and will further explore the contribution of these
spore surface modifications to C. difficile infection.
2021 Microbiology Honours Projects | 1314 | 2021 Microbiology Honours Projects
Associate Professor Sheena McGowan
EMAIL sheena.mcgowan@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9902 9309
OFFICE Room 137, 19 Innovation Walk (Building 76)
WEB https://www.monash.edu/discovery-institute/mcgowan-lab/home
A/Professor Sheena McGowan Inhibition of M1 and M17 starves the malaria parasite
The McGowan laboratory is interested in characterising new Development of Phage Lysins
drug targets. The lab has a strong research focus in the design
of novel anti-malarial drugs as well as other parasitic and
as Novel Antimicrobials
bacterial diseases. Primarily we are a structural microbiology A/Professor Sheena McGowan
laboratory using techniques in protein structural biology, The growing problem of antibiotic resistance underlies the
biochemistry and molecular biology to analyse drug targets of critical need to develop new treatments to prevent and
interest. We use this mechanistic information to design inhibitors control resistant bacterial infections. Exogenous application
or analogues with potential applications in human medicine. of bacteriophage lysins to dormant and actively growing
The laboratory has close connections with both the Department cell cultures results in rapid cell death. Understanding the
of Biochemistry and the Monash Institute of Pharmaceutical mechanism of action will allow the development of lysins
Sciences (in Parkville). as a next generation antimicrobial agent.
The general projects are outlined below and interested students
are encouraged to contact Sheena with any questions or to Antimicrobial Effectors from
discuss further.
Acinetobacter baumannii
A/Professor Sheena McGowan and
Penicillin Binding Proteins A/Professor John Boyce
of Clostridioides difficile Acinetobacter baumannii is recognized as one of the three
A/Professor Sheena McGowan and most important Gram-negative hospital-derived pathogens.
Professor Dena Lyras A. baumannii isolates resistant to all available antibiotics have
The human pathogen Clostridioides difficile produces spores already been identified in patients and there is an urgent
as part of the bacteria’s mechanism of survival when confronted need to find new methods to control A. baumannii infections.
by antibiotics that lead to recurrent and debilitating infection Interestingly, A. baumannii encodes an arsenal of lethal toxins
particularly in hospital environments. We have discovered a designed to directly kill competing bacteria and we believe that
set of penicillin binding proteins normally responsible for the these toxins are a rich source of new antibacterial molecules.
biosynthesis of the bacterial cell wall that are also required This project aims to characterise the structure and function
for the formation of spores. This project will advance of these novel toxins and assess their suitability as potential
our understanding of the link between antibiotic use and new antimicrobials.
sporulation, and provide a path to new drugs for prevention of
sporulation.
2021 Microbiology Honours Projects | 15Dr Greg Moseley
EMAIL greg.moseley@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9905 1036
OFFICE Room 136, 19 Innovation Walk (Building 76)
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.
Dr Greg Moseley
Viruses pose one of the grand challenges to human and animal Elucidating the Rabies Virus P Protein Axis
health globally and within Australia. Viral disease progression
is critically dependent on the formation of specific interaction Dr Greg Moseley, Dr Stephen Rawlinson and
Dr Michelle Audsley
networks between viral proteins and host cell factors, which
enable viral subversion of important cellular processes such as Rabies is a currently incurable disease that has the highest
antiviral immunity and cell survival. fatality rate of known infectious diseases. The etiological agents
of rabies are lyssaviruses, such as rabies virus and Australian
We use advanced cellular/molecular biology approaches
bat lyssavirus. Despite a very limited genomic capacity these
including quantitative proteomics, structural biology, functional
viruses are able to mediate replication, assembly and budding,
genomics, immune signalling assays, and live-cell super-
while simultaneously arresting potent control over the infected
resolution imaging to elucidate these interactions at the
cell and host immune system. Central to this is the expression
molecular and cellular level, and viral reverse genetics and
of multifunctional proteins including P protein, which resides
in vivo infection models to define their functions in disease.
at the core of the virus-host interface where it forms a myriad
Our major focus is on highly lethal human viruses including of interactions with viral and host proteins. We showed that
rabies, Australian bat lyssavirus, Nipah, Hendra, and by inhibiting such interactions, we can prevent otherwise
SARS-CoV-2, as well as a number of agriculturally significant invariably lethal rabies disease, identifying the P protein ‘axis’
and potentially zoonotic animal viruses. The overarching as a therapeutic target. However, the molecular/structural
aim of the research is to identify novel targets and strategies mechanisms by which this small protein coordinates/regulates
for the development of new vaccines and therapeutics for its diverse interactions remain unresolved, leaving major gaps
currently incurable viral diseases. in knowledge concerning fundamental processes in a lethal
The research involves extensive collaborations within Monash human disease.
University and other leading national (e.g. University of Melbourne, The project will seek to define the specific molecular surfaces
CSIRO-AAHL high-containment facility) and international institutes mediating key interactions of P protein, and to analyse
(e.g. Pasteur Institute and CNRS, Paris; Gifu and Hokkaido their function using mutagenesis. This will contribute to the
Universities, Japan; Dundee University (UK)), enabling access elucidation of the structural organisation and regulatory
to unique resources and technologies including novel and highly mechanisms of the virus-host interface and help to define
pathogenic viruses. novel mechanisms by which viruses efficiently co-regulate
host cell subversion and replication. These findings have the
potential to redefine our understanding of the relationship of
viruses and their hosts, and to provide critical tools and data
for the development of new vaccines and antivirals.
16 | 2021 Microbiology Honours ProjectsViral Reprogramming of Host Super-Resolution Analysis of the
Cell Signalling Virus-Host Interface
Dr Greg Moseley, Dr Stephen Rawlinson and Dr Greg Moseley and Dr Toby Bell
Dr Michelle Audsley
Viruses are experts at remodelling the infected cell, and can
Central to the spread of pathogenic viruses is their capacity fundamentally alter cellular biology to transform host cells
to interfere with host immunity, in particular the antiviral system into efficient virus factories. Although molecular/ biochemical
mediated by cytokines such as the interferons. It is well known evidence indicates that certain viral proteins can functionally
that many viruses target signalling by antiviral type I interferons modify structures such as the mitochondria, cell membranes,
to shut down the expression of interferon-stimulated genes. nucleus, and cytoskeleton, understanding of the physical
However, our recent work has indicated that the interaction effects on these structures is limited due to the poor resolving
of viruses with cytokine signalling pathways is much more power of standard cell imaging approaches. Using single
complex and intricate than previously assumed. molecule localization techniques to surpass the physical
In particular, we and our collaborators have found that rabies diffraction limit of visible light, we have developed methods
virus, the cause of c. 60,000 human deaths/year, interacts to observe and quantify the effects of viral proteins on cellular
with multiple signalling pathways, including those initiated by structures at super-resolution, enabling us to directly measure
interleukin-6 and interferon-a/ß using a number of mechanisms viral remodelling of the subcellular environment. Using this
including viral interactions with and remodelling of cellular approach, we demonstrated that virus protein targeting of
structures of the cytoskeleton and nucleus. Importantly, using the cytoskeleton correlates with the capacity to cause lethal
mutagenic analysis and viral reverse genetics, we found that disease in vivo. The project will apply state-of-the-art single
altering viral targeting of these pathways profoundly inhibits molecule localization techniques such as 3D dSTORM to
pathogenesis in vivo, indicative of critical roles in disease. define viral effects on cellular structures in unprecedented
detail; this will provide new insights into the ways that viruses
We are currently seeking to delineate the precise mechanisms co-opt cellular function to cause disease.
by which viruses, such as rabies, SARS-CoV-2 and Ebola
interfere with and modulate cellular pathways, not only to
inhibit antiviral signalling, but also to reprogram specific
Why do Cytoplasmic RNA Viruses
signalling pathways toward ‘pro-viral’ responses, Target the Nucleolus?
a novel concept in viral biology. Dr Greg Moseley and Dr Stephen Rawlinson
Many diverse viral proteins have evolved independently to
Can Rabies Cure Alzheimer’s? target the nucleolus but this phenomenon had been largely
Dr Greg Moseley, Dr Stephen Rawlinson and overlooked, particularly for RNA viruses that replicate within
Dr Michelle Audsley the cytoplasm. Following the development of advanced
‘systems-biology’ approaches to analyse nucleolar biology, it
Neuroinflammation is a major factor in human pathologies such
has become clear that the nucleolus, previously viewed solely
as stroke, Alzheimer’s disease (AD), and traumatic brain injury
as a factory for ribosome production, is in fact a complex,
(TBI). Viruses such as the lyssaviruses rabies and Australian
dynamic, and highly multifunctional machine that coordinates
bat lyssavirus, paramyxoviruses Nipah, Hendra, measles,
many critical cellular processes including immunity and cell
coronaviruses, and the filovirus Ebola, have evolved powerful
survival. This has redefined our understanding of the nucleolus
mechanisms to shut down inflammatory signalling as part of
and suggests that the virus:nucleolar interface might represent
their strategies for immune evasion. We aim to discover the
a central hub for viral hijacking of cellular processes, important
molecular ‘tricks’ used by viruses to subvert host immunity,
to viral replication and pathogenesis.
and to exploit these mechanisms to develop new methods
to efficiently prevent the inappropriate immune responses Using nucleolar proteins from the highly pathogenic RNA
underlying neuroinflammatory disorders. viruses rabies virus and Hendra virus, we are investigating
in molecular detail the mechanisms by which viruses can
We have made major advances in understanding how viruses
reprogram the nucleolus to alter cellular biology. These
achieve immune evasion, including defining the specific virus-
studies are identifying for the first time specific nucleolar
host interactions involved, and the molecular basis of these
functions for RNA virus proteins. The project will advance
interactions. Using this knowledge, and established models
this work, utilizing techniques including molecular biology,
of stroke, TBI, AD and Parkinson’s disease, the project will
proteomics, confocal/super-resolution microscopy, virus
investigate the potential of harnessing viral immune evasion
replication and gene expression assays, and siRNA/CRISPR/
to combat immune disorders.
Cas gene knockout approaches to delineate the precise
events underlying cellular dysfunction caused by virus-
nucleolus interaction. [This project will be in collaboration
with the CSIRO-AAHL PC4 high-containment laboratories
in Geelong.]
2021 Microbiology Honours Projects | 17Professor Anton Peleg
EMAIL anton.peleg@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9902 9159
OFFICE Room 153, 19 Innovation Walk (Building 76)
Professor Anton Peleg Use of infection models to study pathogenesis
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.
18 | 2021 Microbiology Honours ProjectsProject 2
In collaboration with Professor Meredith O’Keeffe
(Dept. of Biochemistry)
The aim of this project is to characterise the activation of
pathogen recognition receptors by our paired susceptible
and resistant clinical isolates. This will be achieved by
studying one of the key first responders of our immune
system; dendritic cells. Different dendritic cell types differ in
their expression of pattern recognition receptors and hence
the types of pathogens that they recognise. They also differ
markedly in their subsequent innate response to pathogens,
with discrete dendritic cell subsets specialised in the
production of different cytokines and interferons. This project
will focus on the differences in pathogen recognition and the
subsequent immune activation between clinically important
and drug-resistant S. aureus strains. Using established
S. aureus mutants, we will also determine the impact of
changes in bacterial surface characteristics on activation of
pathogen recognition receptors.
Characterising Novel Virulence Mechanisms
in the Emerging Hospital-Acquired
Pathogen; Acinetobacter baumannii
A/Professor John Boyce, Dr Faye Morris and
Professor Anton Peleg
Small RNA (sRNA) molecules play important roles in
the regulation of a wide range of bacterial phenotypes
including virulence. Together with Dr Gerald Murray we have
previously determined which A. baumannii sRNA molecules
are expressed in vivo during a mouse infection model. We
predict that sRNAs expressed at high levels in vivo will have
a role in regulating A. baumannii virulence factors. We have
generated an assortment of individual sRNA mutants and in
this project, we will select those that are highly expressed
in vivo and complement the mutants by generating individual
constructs expressing the relevant sRNA from different
promoters. By comparing our repertoire of strains (ie sRNA
mutants, complements and overexpression strains) we
will analyse the effects on a range of virulence associated
phenotypes (growth in human serum, biofilm formation,
and mouse infection models), with a view to identify and
confirm the sRNA specific targets using high-throughput
proteomics and RNA sequencing of sRNA-mRNA duplexes.
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.
2021 Microbiology Honours Projects | 1920 | 2021 Microbiology Honours Projects
Associate Professor Anna Roujeinikova
EMAIL Anna.Roujeinikova@monash.edu
TWO VACANCIES
TELEPHONE +61 3 9902 9194
OFFICE Room 151, 19 Innovation Walk (Building 76)
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.
2021 Microbiology Honours Projects | 21Professor 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
Professor Stephen Turner
Assessing the Role of GATA3 in Regulating
Influenza-Specific Killer T Cell Immunity
Professor Stephen Turner and Dr. Jasmine Li
Virus infection results in T cell activation that triggers large-
scale changes in the phenotype and function of killer T cells
that are critical for immune function, yet the gene regulatory
mechanisms that control these changes are largely unknown.
GATA3 is a transcription factor that is normally associated
with generation of CD4+ T cell responses; however, it has
recently been shown to also be expressed in virus-specific
CD8+ T cells. Our lab has recently shown that GATA3 can
bind to gene regulatory elements assocaited with signature
effector genes within virus-specific CD8+ T cells. This
project aims to use mice where GATA3 deletion is limited to
CD8+ T cells to assess the impact of GATA3 deficiency on
influenza A virus-specific T cells responses. This project will
use a combination of virology, cellular immunity, molecular
biology and biochemistry to assess the impact of GATA3
deficiency on influenza A virus-specific killer T cell function
and establishment of immunological memory.
Figure 1. Naive T cell activation results in structural changes in the genome
that exposes transcription factor binding sites. GATA TF binding are become
accessible after 24 hours of activation. This project will assess whether these
genome elements do in fact become targets for GATA3 binding.
22 | 2021 Microbiology Honours ProjectsProjects Based at
Affiliated Institutions
2020 Microbiology Honours Projects | 23
2021Hudson 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)
Helicobacter pylori Interactions with the Regulation and Biological functions of
Innate Immune System: The Impact of a novel NLR protein, NLRC5, in H. pylori
These Interactions on Inflammation and Infection
Stomach Cancer Professor R. Ferrero and Dr L. Ying
A hallmark of H. pylori infection is the chronic inflammation The new NLR family member, NLRC5, is a key transcriptional
that precedes the development of severe diseases, including coactivator of genes required for MHC class I presentation
stomach cancer. The major research theme in our laboratory is and has been reported to play a role in innate immune responses
focused on understanding how H. pylori induces inflammation to several intracellular pathogens. Interestingly, it was recently
and how this promotes stomach cancer in some individuals. shown that low levels of NLRC5 expression are associated
This theme is addressed through the study of host-pathogen with poor patient prognosis in cancer, leading to the suggestion
interactions using various in vitro and in vivo models. We are that NLRC5 may also be important in tumour surveillance.
particularly interested to understand the mechanisms by which Data from our laboratory suggest that H. pylori bacteria regulate
H. pylori engages with the innate immune system to not only NLRC5 expression thereby dampening inflammation and
cause inflammation, but to also maintain tissue homeostasis. stomach cancer development. The overall aim of the project
For this, our research has centred on members of a family of is to investigate NLRC5 expression and its downstream
cytosolic innate immune molecules, known as the NOD-like signalling functions in response to H. pylori infection. This will be
receptors (NLRs), which are able to sense the presence of addressed in both in vitro and in vivo models, including Nlrc5
both endogenous and exogenous “danger” signals. Although knockout mice. The project will involve a variety of techniques,
NLRs were first identified for their ability to mediate host defence including the culture of primary cells, cell transfection, mouse
responses against infection by microbial pathogens, it is now infection, histological analyses, cytokine ELISA and quantitative
clear that these proteins have much more diverse functions. PCR.
24 | 2021 Microbiology Honours ProjectsYou can also read
