2021 Biochem and Genetics Honours Projects

2021 Honours
Research
Projects
Biochemistry &
Genetics
School of
Cancer Medicine
School of Molecular Sciences/

LIMS
latrobe.edu.au/lims
2021 HONOURS RESEARCH PROJECTS
DEPARTMENT OF BIOCHEMISTRY & GENETICS
SCHOOL OF CANCER MEDICINE
TABLE OF CONTENTS
WHY DO HONOURS? .............................................................................................. 3
COURSE STRUCTURE .............................................................................................. 4
PROJECT ALLOCATION PROCESS ............................................................................. 5
THE DEPARTMENT OF BIOCHEMISTRY & GENETICS................................................. 6

PROFESSOR MICHAEL FOLEY ........................................................................................ 8
DR DAVID GREENING .............................................................................................. 10
ASSOCIATE PROFESSOR BEGOÑA HERAS........................................................................ 12
PROFESSOR MARK HULETT ........................................................................................ 14
PROFESSOR PATRICK HUMBERT ................................................................................. 16
PROFESSOR MARC KVANSAKUL................................................................................. 18
PROFESSOR SURESH MATHIVANAN ........................................................................... 20
PROFESSOR ROBYN MURPHY..................................................................................... 22
DR JACQUELINE ORIAN ............................................................................................. 24
ASSOCIATE PROFESSOR HAMSA PUTHALAKATH ............................................................ 26
DR NICHOLAS REYNOLDS ......................................................................................... 28
ASSOCIATE PROFESSOR HELENA RICHARDSON .............................................................. 30
DR TATIANA SOARES DA COSTA ............................................................................... 33
DR LAKSHMI WIJEYEWICKREMA .............................................................................. 35
OLIVIA NEWTON-JOHN CANCER RESEARCH INSTITUTE ......................................... 37

DR MICHAEL BUCHERT ............................................................................................ 39
DR ASHWINI CHAND ................................................................................................ 40
PROFESSOR MATTHIAS ERNST .................................................................................... 42
DR ERINNA LEE & ASSOCIATE PROFESSOR DOUG FAIRLIE................................................. 44
PROFESSOR JOHN MARIADASON............................................................................... 46
DR DELPHINE MERINO & DR JEAN BERTHELET ............................................................ 48
DR LISA MIELKE ...................................................................................................... 49
DR BHUPINDER PAL .................................................................................................. 50
DR NORMAND POULIOT........................................................................................... 51
RANKED ENTRY PROJECT SELECTION FORM ......................................................... 53
BIOCHEMISTRY & GENETICS Page | 1

WHY DO HONOURS?
Honours in Biochemistry and Genetics will kick-start your career in science. The
Biochemistry and Genetics Honours program equips graduates with technical, analytical,
communication and time management skills
demanded by employers in diverse scientific
fields ranging from biotechnology to
biomedicine. Our students work within teams
to undertake novel research projects under
the supervision of leading scientists.
Honours projects are carried out in state-of-
the-art research facilities, either within the La
Trobe Institute for Molecular Science (LIMS)
on the La Trobe University Bundoora
campus, or at the Olivia Newton John
Cancer Research Institute (ONJCRI) in
Heidelberg.
Objectives
• Extend knowledge of biochemistry, molecular genetics and medical biology
• Obtain an immersive scientific experience in an authentic research laboratory
• Plan and perform cutting edge experimental procedures
• Pursue an original research project to generate new knowledge
Skills you will learn

• Analyse and integrate research findings from numerous sources to formulate
hypotheses
• Design and perform experiments using multiple advanced techniques to investigate
complex scientific questions
• Critically interpret experimental data in the context of other results and prior literature
• Develop excellent time management skills
• Develop advanced scientific oral and written communication skills
• Work collaboratively as part of a cohesive and productive research team
Past student testimonials

• Honours was an incredibly stimulating learning experience
• It was an amazing year which provided me with real research skills
• The lab experience was invaluable
• The independent research project was intellectually challenging
• Working in a biomedical research lab gave me a sense of contribution to society
• My honours project lead to a research publication, which set up my career

COURSE STRUCTURE
Honours projects are available in the disciplines of Biochemistry, Molecular Genetics or
Biomedicine, and can be performed either at the La Trobe Institute for Molecular Science
(LIMS), La Trobe University, (Bundoora campus) or within the Olivia Newton-John Cancer
Research Institute (ONJCRI), Austin Hospital (Heidelberg), which is affiliated with the School
of Cancer Medicine. All students, regardless of the location of their chosen laboratory, must
attend compulsory sessions (e.g. training, assignments) on the Bundoora campus at La
Trobe University.
The course will commence on Thursday 4th February 2021 with a series of compulsory
induction lectures. After this, students will write a literature review that summarises relevant
prior knowledge and present an introductory seminar to the department (accounting for 8%
of the year’s assessment). The majority of the year is dedicated to performing novel
research, under the supervision of the laboratory head and other senior staff. Throughout
the year, students will learn about diverse research topics through attending research
seminars delivered by invited experts (1%). In May, Honours students will complete a
module introducing them to advanced biotechnology techniques (10%) and in August they
will create and present a poster outlining the goals of their project and their progress to that
point (8%). In September, students will complete their experiments to focus exclusively on
writing their theses, which will be submitted in mid-October (40%). Supervisors will
continuously assess students’ laboratory performance throughout the year (10%). The year
culminates in late October, with students delivering seminars summarising their research
findings to the department (8%) and undertaking oral examinations (15%).
At the end of the course we expect our students to be able to enter the work force and
perform competently at whatever tasks they are given. Indeed, graduates from our Honours
program are highly sought after by universities (both nationally and internationally), research
institutes, hospitals and biotech companies alike.
Choosing an Honours Project

There are a number of things to consider before deciding which supervisor/laboratory is best
for you. These include:
Research topic: Which research questions and techniques do you find most interesting and
appealing? To what extent will the background knowledge you gained through your
undergraduate studies prepare you for each of the research topics?
Supervisor: What supervisory style suits you best? Would you prefer to receive day-to-day
supervision and feedback regarding practice presentations and thesis drafts predominantly
from the laboratory head or from a team that may include postdoctoral fellows and research
assistants?
Career opportunities: How will each of the possible projects equip you for your chosen
career, including possible postgraduate research (if applicable).
These questions can be answered through discussions with prospective supervisors,
postgraduate students and current Honours students. Don’t be afraid to ask!

PROJECT ALLOCATION PROCESS
Eligibility: Students must complete at least one of the following subjects MED3LAB or
GEN3LAB. Some projects may have additional background requirements so check the
project descriptions carefully. However mere completion of a pre-requisite subject will not
guarantee entry into the course as there are a limited number of places available. Students
MUST discuss projects with prospective supervisors.
To organise an Honours research project and supervisor:

1. Read this booklet carefully.
2. Attend the online information session presentations via Zoom (TBA – late September).
3. Email any prospective supervisors who have offered projects that you find interesting
and would consider undertaking to organise appointments to discuss the proposed
projects and your suitability. You can explore the possibility of securing “select” entry
into your preferred laboratory during these meetings.
Note: Students MUST meet with a supervisor in order to be placed in their laboratory. To
maximise your chance of being accepted into the Honours program we recommend
you meet with AT LEAST FIVE supervisors.
There are two allocation routes: “select” (by negotiation) and “ranked” (based on marks).
If your meeting with a supervisor leads him/her to offer you a “select” place in his/her
laboratory, and you accept, ensure that the supervisor notifies the course co-ordinator
(i.poon@latrobe.edu.au) (cc’ing you) by Friday 30th October, 2020.
If you do not arrange “select” entry by Friday 30th October, you can apply to gain “ranked”
entry into the course by ranking the supervisors you met with on the attached nomination
form (page 52 of this booklet).
“Ranked” entry will be determined by your final average marks in third year biochemistry,
molecular genetics or biomedical science subjects. This means students with better marks
have a higher chance of being assigned to their preferred supervisor.
To apply for “ranked” entry into Honours fill out the form on page 53 of this booklet, specifying
your ranking for each supervisor who you have met.
Submit the form to i.poon@latrobe.edu.au by 5pm Friday 6th November, 2020.
Provisional offers will be made via email in late November (subject to ratification by the
University of semester 2 marks) so make sure you check your university email account
during this period.
If you have any questions about the allocation process, of the Honours course, please e-
mail i.poon@latrobe.edu.au to make an appointment.

THE DEPARTMENT OF BIOCHEMISTRY & GENETICS
The Department of Biochemistry and Genetics is engaged in both fundamental and
commercially driven research. It has a strong record of attracting competitive funding from
National (i.e. the Australian Research Council (ARC), the National Health and Medical
Research Council (NHMRC)) and international (i.e. National Institutes of Health) funding
agencies. The Department has published numerous papers in highly influential journals such
as Cell, Science and Nature. Research conducted within the Department has led to the
generation of valuable intellectual property. The Department currently houses three
biotechnology companies involved in product development and marketing.
Around a third of our Honours graduates progress their research careers by undertaking
PhDs. Many perform their postgraduate research in our department but some move to other
institutions in Victoria, interstate or overseas for this stage of their careers. For example,
Charlotte Dawson (Honours 2018) was recently awarded a prestigious Herchel Smith PhD
scholarship to undertake a PhD at the University of Cambridge in the United Kingdom.
During their PhDs many of our Honours graduates successfully apply for funding to attend
international conferences. Amy Pascoe (Honours 2018) received a travel award to present
her data at the upcoming European Muscle Conference, which was held at the University of
Kent (United Kingdom).
Our graduates are highly employable, being sought after by other universities and research
institutes, as well as biotechnology companies. Many of our Honours/PhD graduates
undertake postdoctoral research, within Australia or overseas. Others, including those listed
below, pursue diverse roles in academia, biotechnology or medicine:
• After occupying a number of senior roles within La Trobe University Damian Spencer
(Honours 2001, PhD 2007) recently accepted a position as Dean (Teaching and
Learning) at Cambridge International College, Australia.
• Dr Nicole van der Weerden (Honours 2003, PhD 2007) is now the Chief Executive
Officer of Hexima (a successful biotechnology company).
• David Bloomer (Honours 2012, PhD 2017) is also working in the biotechnology industry,
within the recombinant proteins sector at CSL.
• Stephanie Paone (Honours 2013, PhD 2018) works as Clinical Research Coordinator
at Nucleus Network.
The Department of Biochemistry and Genetics contains 27 research laboratories, teaching

facilities and administration across two buildings (LIMS1 and 2). These buildings contain
state-of-the-art facilities with 10,000 m2 of usable space including 18 new research and
support laboratories, an equipment barn, and ~ 3,000 m2 of teaching facilities.

Research at LIMS is aimed at
generating Translatable Molecular
Discoveries and encompasses
research in four thematic areas:
Cancer, Infection and Immunity,
Molecular Design and Nanoscience.
Facilities include:
• Confocal and widefield microscopy (for imaging fluorescently labelled biomolecules in

fixed and live cells)
• FACS/flow cytometry (analyses or sorting of cells based on surface markers or other
features)
• Fluorescence spectroscopy (for sensitive detection of intrinsically and extrinsically
labelled fluorescent biomolecules)
• Gel doc and Chemidoc systems (for stain free analysis and Western blotting)
• Gel electrophoresis equipment (for separating proteins, DNA and RNA)
• Histology preparation equipment (staining of biological tissue samples)
• Ion S5 next generation sequencer (for small RNA profiling and targeted DNA
sequencing)
• Liquid chromatography systems (for protein purification)
• Mass spectrometry (for protein/peptide sequencing, and identification/quantification of
proteins in complex samples)
• Protein interaction facility (including Analytical ultracentrifugation, Isothermal Titration
microcalorimetry and Surface Plasmon Resonance) for measuring biomolecular
interactions
• Microscale thermophoresis instrumentation (for quantification of protein-protein and
protein-ligand interactions)
• Plate readers (for UV/Vis, luminescence and fluorescence assays in 96- and 384-well
plate formats)
• qRT-PCR systems (for quantification of gene expression) and automated liquid
handling instruments
• Tissue culture facilities (for bacterial, insect, mammalian, plant cell and viral culturing)
• UV/Vis spectroscopy (for quantifying DNA, RNA, peptides & proteins and performing
enzyme kinetics assays)
• X-ray crystallography (for determining the three-dimensional structure of proteins and
biomolecular complexes).

Professor Mick FOLEY
SHARK ANTIBODIES AS HUMAN THERAPIES
Office: LIMS2, room 217
Phone: 9479 2158
E-mail: m.foley@latrobe.edu.au
Subjects prerequisites: MED3LAB and/or MED3PRJ
LIMS theme: Infection and Immunity
Positions available: One
Project Description
Shark antibodies (IgNARs) are a subset of antibodies found in sharks, rays and other
cartilaginous fish. Some IgNARs have been shown to possess
an elongated CDR3 loop, that is significantly larger those of
human and murine antibodies. The IgNAR extended CDR3 loop
is considered to be ideal for targeting cleft-type epitopes such as
enzyme active sites and surface receptors which are otherwise
inaccessible to conventional antibodies. Using Plasmodium
falciparum as a model system we have identified peptides and
shark antibodies that block invasion of malaria parasites into host
erythrocytes. The structure of the complex of this IgNAR and its
target revealed that the IgNARs penetrate a hydro- phobic trough
on the malarial protein. Therefore, this class of antibodies may
be able to penetrate into important functional sites on proteins
and modulate their function.
Recently we have created a humanized version of these antibodies and have identified
antibodies from this library that bind to the chemokine receptor CXCR4 (Journal of Biological
Chemistry (2016) 291:12641-2657). This molecule is up-regulated in many cancer cells and
is an important target in fibrosis. Fibrosis is a scarring of the tissues due to repeated damage
or infection. We are therefore exploring the use of these antibodies in both cancer and
fibrosis. These antibodies can bind to and block the growth of cancer cells as well as block
inflammatory cells from migrating towards the site of inflammation. Moreover, these
antibodies can prevent the development of lung fibrosis in an animal model (Scientific
Reports (2018) 8:3212). Indeed, we have initiated our first clinical trials in humans of our anti

fibrotic i-body called AD-214 to assess its safety.
Wynn T, J Exp Med 2011
This honours project will examine the mechanism of action of these antibodies in either
cancer or fibrosis with a view to developing improved molecules to progress towards human
clinical trials. In addition, we have the potential to identify novel i-bodies to important
molecular targets involved in the fibrotic pathway.

Dr David GREENING
MOLECULAR PROTEOMICS GROUP

Office: Baker Heart Institute, Alfred Health Campus, Prahran
Phone: 8532 1186
E-mail: david.greening@baker.edu.au / d.greening@latrobe.edu.au
Subjects prerequisites: MED3LAB, MED3PRJ or GEN3LAB
LIMS theme: Cancer, Nanoscience
The Molecular Proteomics laboratory is focused on understanding the molecular

composition and function of nano-sized extracellular vesicles and how their intercellular
signalling is important in normal physiology and pathologies; including cancer and
cardiometabolic disease. We use a multi-disciplinary approach to understand the molecular
composition and function of extracellular vesicles incorporating proteomics, cell biology,
molecular biology, nanobiotechnology, functional assays, cell and animal models, with the
goal of understanding mechanisms of cell signalling and function, identifying deliverable
therapeutic targets and engineering nanoparticles for next generation cell-free therapies.
Understanding the roles of extracellular vesicles during cardiac fibrosis

Co-supervisor: Dr Alin Rai (Baker Inst.)
Heart failure occurs when the heart loses the ability to pump sufficient blood to metabolising
tissues and is the leading cause of death in today’s society. The most common contributing
factor of heart failure is cardiac fibrosis, which arises from most cardiovascular pathologies
including myocardial infarction (heart attack) and hypertension (high blood pressure). For a
pathology that carries such clinical significance, the mechanisms behind cardiac fibrosis are
poorly understood. However, secreted signalling factors have been implicated in fibrotic

alterations important to the progression of cardiac fibrosis.
Yet our understanding of the mechanisms involved in inter-cellular signaling leading to this
fibrotic cardiac pathology remains limited. A major emerging player in intercellular
communication is a class of extracellular vesicles (EVs) called exosomes. Exosomes are
nano-sized lipid-encapsulated vesicles that contain RNA and proteins which can mediate
intercellular signalling to elicit a functional response. Although exosomes are established to
activate fibrotic processes, their role in the development of cardiac fibrosis remains poorly
understood. Here, we aim to investigate the signals released from endothelial tissue, an
understanding of exosome composition during cardiac fibrosis, and establish the functional
role of exosomes during the development of cardiac fibrosis.
To achieve this, we will employ cell models of human cardiac fibrosis, extracellular vesicle
purification & characterisation, high-resolution mass spectrometry-based proteomics, data
science and informatics, nano-scale functional assays, fluorescence microscopy, and
microwestern blotting (dot blot). This will help define the cargo of exosomes and
mechanisms which temporally regulate the progression of cardiac fibrosis. Importantly, this
will help identify likely contributors of disease pathology which can guide design of novel
nano-based therapeutics.
Upon completion of the Honours year, we expect our student to be equipped with
fundamental laboratory techniques in cell and molecular biology, protein biochemistry,
proteomics, data science/informatics, and confocal imaging.

Associate Professor Begoña HERAS
BACTERIAL VIRULENCE FACTORS:
STRUCTURE & FUNCTION
Office: LIMS 1, Room 525
Phone: 9479 3185
E-mail: b.heras@latrobe.edu.au
LIMS theme: Infection & Immunity
Bacterial resistance to antibiotics is increasing at an alarming pace with fears that we could
return to the pre-antibiotic era where bacterial infections were virtually untreatable. There is
an urgent need to increase our understanding of the mechanisms underlying bacterial
pathogenesis to identify new targets for therapeutic intervention. In the Heras laboratory we
are investigate the virulence mechanisms in Gram-negative bacteria in order to develop
antibacterial drugs with novel modes of action.
Disarming bacteria: understanding the structure and function of bacterial toxins

Co-supervision: Dr Jason Paxman
Pathogens rely on an arsenal of virulence factors, to attach and infect their host.
Autotransporter (AT) proteins are a major group of virulence proteins that bacteria use to
establish highly persistent infectious diseases
In this project we will investigate a k e y A T s u b g r o u p ,

the Serine Protease Autotransporters of
Enterobacteriaceae (SPATEs). These secreted trypsin-
like serine proteases are associated with virulence
functions such as colonisation, invasion and toxicity. We
will focus on key SPATE proteins from pathogens like
Shigella and Escherichia coli which cause diarrheal
diseases and urinary tract infections and are among the
most common infectious diseases of humans.
Crystal structure of the
autotrasnporter adhesin UpaB
The outcomes of this research will contribute to a better understanding of the biology of

Gram-negative pathogens. Furthermore, this work will provide valuable structure - function
information that will be the all-important basis for the development of new and more
effective antibacterial therapeutics, a subject of major significance given that these
pathogens are becoming increasingly resistant to current antibiotics.
Application of a fragment based drug discovery approach for developing anti-neisserial
agents
MDR pathogens include Neisseria gonorrhoeae the causative agent of sexually
transmitted gonorrhoea, which was recently classified as one of the ‘top urgent threats to
global health, due to their increasing resistance to antimicrobials. The overall goal of this
work is to develop narrow spectrum anti-neisserial therapeutics.
Bacteria contain
periplasmic Disulfide Bond
(Dsb) forming enzymes to
catalyze the folding of
many virulence proteins.
These Dsb catalysts are
are currently being
investigated as potential
targets for the
development of
antivirulence agents.
DsbD,a member of the Dsb Fragment-based drug discovery (FBDD) approach: Involves
family is an essential screening small fragments for the development of drugs
enzyme for the viability of
Neisserial pathogens.
In this project a fragment-based drug design approach that combines NMR spectroscopy,
X-ray crystallography and electron transfer assays will be employed to identify small
molecules that bind to the catalytic domains of DsbD.
The binding mode and potency of

these fragments will be
investigated and their inhibitory
activity tested using electron
transfer in in vitro assays.
Elaboration of these hit fragments
will also be performed to obtain
potent Neisserial DsbD inhibitors.
The outcome of this work is the
development narrow spectrum
antibiotics against Neisserial
infections.

Professor Mark HULETT
INHIBITING TUMOUR METASTASIS &
INFECTIOUS DISEASE
Phone: 9479 6567 E-mail: m.hulett@latrobe.edu.au
Subjects prerequisites: MED3LAB, MED3PRJ and/or GEN3LAB
LIMS themes: Cancer, Infection & Immunity
Cancer and infectious diseases are major global health problems. There is an urgent need
for more effective anti-cancer therapies and new antibiotics to address the rise of
antimicrobial resistance. Our research focuses on two key areas (i) defining the molecular
basis of the enzyme heparanase in tumour progression to develop inhibitors as anti-cancer
drugs, and (ii) understanding the mechanism of action of innate defense peptides against
target cells for development as anticancer and antimicrobial therapeutics. In consultation
with prospective honours students we will “tailor” design projects that are appropriate to your
interests under the following themes.
Heparanase function in tumour progression
The ability of malignant tumour cells to escape from primary tumour sites and spread through
the circulation to other sites in the body
(metastasis) is what makes cancer such
a deadly disease. An essential process in
metastasis is cell invasion - where tumour
cells move into and out of the
vasculature. Cell invasion is also a critical
event in
the migration of white blood cells of
the immune system (leukocytes) to
sites of inflammation to combat
infections. The heparan-sulphate (HS)-
degrading enzyme has been shown to
play a key role in the degradation of
extracellular matrices and its activity
strongly correlates with the metastatic capacity of tumour cells and the migratory capacity of
leukocytes. We have shown that heparanase is the dominant HS- degrading enzyme in
mammalian tissues, making it an attractive drug target. We are currently working towards (i)
further understanding the molecular basis of heparanase function, (ii) defining the
dysregulation of heparanase gene expression in cancer, and (iii) using heparanase knockout

mice in disease models to define the precise role and contribution of heparanase in tumour
progression. Our overall goal is to better understand the biology and action of heparanase
to enable the development of specific inhibitors of the enzyme, which will lead to new drugs
for the treatment of tumour growth and metastasis. See: Journal of Clinical Investigation
(2017) 127:2777.
Innate defense molecules as novel antimicrobial and anti-cancer agents
Defensins are innate immune molecules

found ubiquitously in the animal and plant
kingdoms that often exhibit broad activity
against microbial pathogens and
mammalian cancer cells. We have
described a conserved mechanism of
action by defensins against pathogenic
bacteria, fungi and enveloped viruses, as
well as cancer cells. The defensins target
and kill such pathogens and cancer cells
using a novel cell lysis mechanism via
direct binding to specific plasma membrane phospholipids. Our aim is to define the defensin
mechanism of action to engineer improved forms for development as novel antimicrobial and
anticancer therapeutics. We have extensive research programs dedicated to (i) investigating
the molecular basis of the antimicrobial and anti-cancer activity of defensins using a range
of biochemical and biophysical methods including in vitro pathogen and cell viability assays,
live cell imaging, electron microscopy and X-ray crystallography (in collaboration with the
Kvansakul lab); and (ii) in vivo testing and pharmacokinetic properties of defensins in models
of infection and tumour progression. See: eLife 3:e01808 (2014), Proc. Natl. Acad. Sci. USA
113:11202 (2016), Nature Communications 9:1962 (2018); Science Advances
4(7):eaat0979 (2018).

Professor Patrick HUMBERT
CELL POLARITY & TISSUE ARCHITECTURE
Phone: 9479 5155
E-mail: p.humbert@latrobe.edu.au
Subjects prerequisites: MED3LAB or MED3PRJ
LIMS theme: Cancer
Topic 1: Cell Polarity and Cancer

In the Humbert Laboratory
researchers investigate the
fundamental role of tissue
organisation and asymmetry on
cancer progression with the aim of
identifying new therapeutic
strategies for the prevention of
cancer. Loss of the proper orientation of cells within a tissue, known as cell polarity, is one
of the earliest hallmarks of breast and prostate cancer and is correlated with more
aggressive and invasive cancers. However how loss of cell polarity occurs and how it
contributes at the molecular level to tumour initiation and progression remains unknown.
Using a number of approaches such as RNAi screening and proteomics, our laboratory has
identified a network of potential new cell polarity regulators and tumour suppressor genes
that share a common function in modulating tissue architecture and key oncogenic
pathways. How these operate to regulate tumour formation is currently unknown. A better
understanding of these new regulators should allow us to design new therapeutic means by
which to prevent epithelial cancer.
Project Description: Cell Polarity Proteins and Cancer
In this project, you will characterise how key polarity regulators and new genes from this
network can supress tissue architecture and oncogenic signalling. A variety of biochemical,
cell biological and functional assays set up in our laboratory will allow you to delineate the
precise molecular mechanisms by which these protein modifications can impact on cancer
signalling and cell transformation. These studies include CRISPR engineering and RNAi
knockdown studies in 3D mammary organoid cultures as well as the analysis of established
genetically engineered animal models including Drosophila, Zebrafish and Mouse. The

above experiments will provide essential information as to the requirement for intact polarity
signalling in cancer development and the signalling pathways regulated by the genes that
control tissue organization to suppress cancer initiation, growth and invasion.
Techniques: Cell culture, CRISPR, RNAi, 3D organotypic cultures, animal models, mass
spectrometry, FACS analysis, Confocal microscopy and histological analysis.
Topic 2: How the Red Blood Cell lost its Nucleus
Erythroid enucleation is the process by which the
future red blood cell (RBC) disposes of its nucleus
prior to entering the blood stream. Although the
process of enucleation has been recognised for more
than a century, the molecular and cellular programs
governing it are still poorly understood. With a large
proportion of cancer and surgical patients undergoing
blood transfusions as part of their treatment, a major challenge for transfusion medicine is
the constant difficulties in obtaining sufficient supplies of specific RBC subtypes. Despite
exciting advances in the in vitro production of human red blood cells from hematopoietic,
embryonic and induced pluripotent stem cells, the reduced ability of these cultured cells to
fully enucleate remains a major hurdle. A better understanding of the enucleation process
should lead to improved strategies for the efficient and rapid production of RBCs for
autologous (i.e. self-generated) patient transfusion.
Project Description: Exploring the role of novel regulators of erythroid enucleation
Using a chemical screening approach our lab has identified a number of new regulators of
the enucleation process. How these control nuclear extrusion is completely unknown. In this
project you will use erythroid culture methods, enucleation assays, CRISPR and RNAi
genetic manipulation, confocal microscopy, FACS analysis and biochemical techniques to
identify how these new regulators control enucleation. Together your studies will provide
insights into how enucleation is regulated and help develop strategies to enhance the
production of red blood cells in vitro for patient transplantation purposes.
Techniques: Primary cell culture and differentiation assays, CRISPR, RNAi, mouse models,
mass spectrometry, FACS analysis, Confocal microscopy and histological analysis.

Professor Marc KVANSAKUL
HOST-PATHOGEN INTERACTIONS
Office: LIMS1, 516
Phone: 03 94792263
E-mail: m.kvansakul@latrobe.edu.au
The lab is interested in the molecular interplay between hosts and their pathogens. Infectious
diseases are a major burden for both human health as well as the agricultural sector. We
study using structural biology techniques how pathogens engage with important host
defence signalling pathways in order to better understand the molecular mechanisms
underlying a range of infectious diseases. We then use our atomic level understanding of
these host-pathogen interactions to develop new therapeutic strategies to curb the rise of
infectious diseases.
Virus-mediated inhibition of programmed cell death

Programmed cell death or apoptosis is a critical process that
allows removal of infected, damaged or otherwise unwanted
cells. Failure to correctly control apoptosis plays an important
role during pathogenic infections, autoimmune diseases and
cancer. Using X-ray crystallography we aim to understand at the
atomic level how certain viruses hijack the host cell’s apoptotic
machinery to ensure their own survival and proliferation. We are
particularly interested in certain poxviruses as well as African
Swine Fever virus. All projects in this area aim to express
milligram quantities of these proteins and biochemically
characterize them using isothermal calorimetry, surface
plasmon resonance or additional functional assays. Once this is completed, we aim to
crystallize these proteins in complex with ligands identified during the initial biochemical
studies.

Structural and functional studies defensin-mediated innate
defence
Defensins are small cationic proteins that are involved in innate
immune processes in plants as well as humans. In plants,
defensins have been shown to deliver significant resistance
against plant pathogens such as fungi, however their precise
molecular mechanism of action is currently not fully understood. In
humans, defensins play a critical role as first line of defence. We
are interested in biomedical applications of defensins from a wide
range of organisms, and together with the Hulett laboratory employ
a strategy based on biophysical methods including X-ray crystallography, electron
microscopy and small-angle X-ray scattering to understand their function.

Professor Suresh MATHIVANAN
EXOSOMES IN CANCER METASTASIS
Phone: 9479 2565
E-mail: S.Mathivanan@latrobe.edu.au
Subjects prerequisites: MED3LAB and/or MED3PRJ and/or GEN3LAB
LIMS theme: Cancer
Positions available: Two
Project #1: Exosomes in cancer metastasis

Exosomes are small extracellular vesicles (30-150 nm) that are released into the
extracellular microenvironment upon the fusion of multivesicular bodies with the plasma
membrane (Fig. 1)1.
Exosomes contain a
cargo comprising specific
proteins, nucleic acids
and lipids that reflect the
pathophysiological state
of the cell of origin.
Exosomes influence
signalling pathways in
the neighbouring cells
and are vital in
intercellular
communication, being
conveyors of nucleic
acids, proteins and lipids. Fig. 1. Schematic representation of EV release1.
It is now well established
that exosomes regulate various processes in favour of cancer progression, including
metastasis, remodelling the tumour microenvironment, immune evasion, coagulation,
vascular leakiness, establishing pre-metastatic niche, tropism for metastasis, transfer of
chemoresistance and cancer cachexia. In this project you will study the therapeutic utility of
exosomes inhibition in highly aggressive models of triple-negative breast and pancreatic
cancer. A range of cell culture and mice models will be utilised to delineate the role of
exosomes in metastasis.

Techniques used: Cell culture, Western blotting, Molecular biology, CRISPR, FACS analysis,
Confocal microscopy, mass spectrometry, qPCR, Mice models and Immunohistochemistry.
Project #2: Cellular senescence in metastasis

Using a cell culture, CRISPR genome editing and mice models, we have recently shown that
cancer cells release more than 3-fold exosomes upon induction of cellular senescence. It
has been previously established that exosomes from cancer cells can establish a pre-
metastatic niche and regulate tropism for secondary cancer sites. In this project, the role of
senescence in accelerating metastasis will be studied by examining the role of exosomes
produced by the senescent cells. As senescence is considered as a double-edged sword,
this project will delineate the role of senescence in accelerating metastasis and allow us to
design strategies to eliminate senescent cells as part of cancer therapy. A range of molecular
biology and biochemical techniques including CRISPR gene knockout, PCR, mass
spectrometry, Western blotting, immunoaffinity assays, confocal microscopy, luciferase
assay and mice models will be employed.
1. Kalra, H.; Drummen, G. P.; Mathivanan, S., Focus on Extracellular Vesicles:

Introducing the Next Small Big Thing. International journal of molecular sciences 2016, 17
(2), 170.

Professor Robyn MURPHY
SKELETAL MUSCLE BIOCHEMISTRY
Phone: 9479 2302
E-mail: r.murphy@latrobe.edu.au

My overall research interest is in the area of skeletal muscle in health and disease. The
research of my group focuses on various aspects of skeletal muscle biochemistry in health
and disease, using exercise and disease models in humans, as well as animal models. In
particular, we measure proteins in segments of individual fibres allowing issues with the
heterogeneity of skeletal muscle to be overcome. We also examine movement of proteins
following micro-dissection of fibres, allowing us to quantitatively assess the redistribution of
proteins following various interventions.
Effect of age and fibre-type on proteins related to autophagy in skeletal muscle function
Co-supervisor: Dr Stefan Wette, Postdoctoral Researcher, Dept of Biochemistry and
Genetics
Ageing is a natural process of life; which has inevitable consequences on the quality of both
skeletal muscle mass (sarcopenia) and muscle strength/function (dynapenia). Both
sarco/dynapenia impair gait and increase the likelihood of a fall by an older adult. Muscle is
heterogenous in nature, and its fibre type composition is dependent on age, disease state
or fitness of a person.
In the elderly, Type II fibres are substantially affected, whereby there is a reduction in the
number of these fibres compared with Type I fibres, along with them being weaker than Type
I fibres, leading to muscle atrophy. Further, many proteins important for muscle metabolism,
contractility and growth are fibre-type specific. Therefore the analysis of proteins in single
fibres allows a thorough investigation of these proteins.
In this project you will assess the abundance of various proteins related to autophagy in
skeletal muscle obtained from both young and older healthy individuals. It is hypothesised
that the most change will be in the Type II fibres of older adults but not in Type I.
This project will see you learning to dissect single fibres from human muscle samples to use
a new approach for rapid and efficient fibre typing of each individual fibre and then to use a

specialised and highly sensitive quantitative Western blotting technique developed in the
Murphy lab to determine the abundance of various autophagy-related proteins. This will be
in addition to possibly utilising whole muscle tissue preparation, cryosectioning of tissue and
immunofluorescence techniques, which will be driven by the particular research question
you wish to address. Time-dependent, you will develop an enzymatic assay for use in the
single muscle fibres.
Other projects are possible by discussion with Robyn. There are many possibilities that fall
under the overall research objectives of the group. These could include animal or human
studies.

Dr Jacqueline ORIAN
NEURODEGENERATION AND NEUROREPAIR
Phone: 9479 1113
E-mail: j.orian@latrobe.edu.au
Subjects prerequisites: MED3LAB, or GEN3LABT
LIMS theme: Infection and Immunity
The major focus of the laboratory is multiple sclerosis (MS), an autoimmune disease of the
central nervous system characterised by infiltration of immune cells, demyelination and
neuronal and axonal loss. MS is typified by an initial relapsing-remitting profile but in over
50% of patients the disease transitions to a progressive form, characterised by relentless
progression. The cause of the disease is unknown and current treatments are of limited
benefit. The project below aims to generate proof of concept that blood cells known as
platelets play a key role in disease development and therefore, represent a novel therapeutic
target for this disease. Experimentation will be based on the experimental autoimmune
encephalomyeltis (EAE) model, which is the most accepted MS model.
Targeting platelets in early multiple sclerosis to prevent entry into the progressive disease
stage.
(In collaboration with Prof K. Peter (Baker Heart and Diabetes Institute) and the Dept. of
Psychology and Counselling, La Trobe Univ.)
The role of platelets as major contributors to vascular homeostasis has been
thoroughly established over decades. However, growing evidence of their role as carriers of
major and abundant pro-inflammatory agents has led to the concept that platelets are also
key players in inflammatory and immune diseases. A collaborative study between Professor
Karlheinz Peter, a vascular biology specialist and our laboratory, generated two major
findings that not only confirm the role of platelets in the inflammatory process but also
suggest an additional function in neurodegeneration in EAE and MS.
1. By inducing platelet depletion at different time points over the course of EAE we were able
to demonstrate a cause-and-effect relationship between platelet accumulation and disease
development. This finding represents a change in paradigm regarding mechanisms
underlying neuroinflammation.
2. We were able to detect platelets in the central nervous system grey matter ahead of

immune cell infiltration. This is a highly important and novel finding. Whilst platelets have
previously been demonstrated in MS and EAE lesions, this evidence had been confined to
white matter. Early entry of platelets in grey matter suggests a mechanism for the earlier
onset of grey relative to white matter pathology, as well as demyelination and neuronal loss
in the absence of large-scale immune cell infiltration.
However, the presence of platelets in grey matter, per se, does not constitute
evidence of a functional role for these elements. The aim of this project is to demonstrate
consequences for the presence of platelets in grey matter. This will be achieved by
addressing common and measurable symptoms associated with both MS and EAE, namely
visual problems and impaired emotion and cognition. These will be assessed using well-
established approaches and comparison of platelet depletion and immunomodulation
treatments. We aim to demonstrate that platelet depletion is more effective than
immunomodulatory treatments in reducing these symptoms.
The significance of this project is that it will explore a hitherto undescribed and
potentially therapeutically targetable mechanism to battle neurodegeneration. It is now clear
that targeting neuronal loss from the earliest disease stage is key to slowing entry into
progressive MS. Our findings are likely to provide new and much needed impetus in
investigations of mechanisms of neuronal loss and the development of new therapies
targeting platelet function for MS.
This project will allow you to acquire basic concepts of neurobiology and immunology
and the validation of animal models to investigate human disease. In addition you will
become proficient in immunochemical techniques, microscopy and behavioural studies.
For more information on MS see https://www.msaustralia.org.au/

Associate Professor Hamsa PUTHALAKATH
N
REW DRUGSDFOR
ATIONAL RUGCANCER
DESIGN SEPSIS
ANDAND AGE-
RELATED
Office: DISEASES
LIMS 2, Room 216
Phone: 9479 5226
E-mail: h.puthalakath@latrobe.edu.au
Phone: 9479 6570 Email: m.perugini@latrobe.edu.au
Positions available: One or two
Apoptosis, a form of programmed cell death, is vital for the development and maintenance
of healthy tissue in the body. It is a key factor in the development of many diseases including
cancer and sepsis. Our lab’s focus is to develop novel drugs for treating chemo-resistant
cancers and for treating sepsis
Project 1. Role of BOK in chemo-resistance
The enigmatic protein BOK is believed to be involved in the mitochondrial apoptosis

pathway. The latest research from our lab (Srivastava et al, 2019, PNAS) shows that it
regulates nucleotide biosynthesis, the same pathway involved in the conversion of 5-FU
(one of the most important chemo-drugs used in treating many cancers) to its toxic
metabolites. Cancers that become resistant to 5-FU down regulates BOK to escape the
toxicity. We have uncovered the structural basis of this regulation and are in the process of
developing novel drugs to re-sensitize the 5-FU resistant cancers.
The project involves molecular modelling and identifying possible drug hits and
characterisation and validation of the drug targets, developing and testing gene therapy

vectors in vitro and in xenograft mouse models.
Techniques: Cell culture, apoptosis assay, organoid culture and confocal microscopy.
Reference: Srivastava et al, PNAS, 2019.
Project 2: Understanding immune cell death during sepsis
Sepsis is the condition of overwhelming systemic microbial infection in which there is
widespread organ damage, frequently leading to a downward spiral and death. Sepsis is
responsible for more than 6 million deaths per year worldwide. Over 18,000 Australians
suffer from sepsis every year and 5000 of these patients die; of those who survive, half are
left with a disability, which may be life-long (George Institute for Global Health, 2017). There
is no effective treatment for sepsis today other than intensive care and antibiotic therapy,
which leaves patients immunosuppressed and vulnerable to nosocomial infections. Using
whole genome CRISPR screening in mice, we identified the receptor Treml4 that causes
sepsis-associated inflammation and immunosuppression in mice. Deletion of this gene
results in almost 100% protection against sepsis-associated mortality in mice and also
against Candidiasis (blood infection by Candida albicans). We have identified the human
homologues of this receptor and in the process of generating monoclonal antibodies and
developing mouse models to study the function of the human receptors.
Techniques: Cell culture, apoptosis assay, confocal microscopy, gene expression analysis
by qPCR/Digital PCR and animal work.
Reference: Nedeva, Menassa et al, Nature Immunology, 2020.

Dr Nicholas REYNOLDS
PEPTIDE NANOFIBRIL BIOMATERIAL SCAFFOLDS
FOR TISSUE ENGINEERING APPLICATIONS
Phone: 9479 1861
E-mail: nicholas.reynolds@latrobe.edu.au
Subjects prerequisites: Nil

LIMS theme: Nanoscience
Peptide Nanofibril Biomaterial Scaffolds for Tissue Engineering Applications

Background
My lab’s research is focussed on the discovery and development of materials based on self-
assembling peptides for various technological applications including tissue engineering and
regenerative medicine.
Effective treatment of degenerative diseases is one of the biggest challenges in healthcare

today. Arthritis alone affects over 4 million Australians and costs $7 billion per year. While
cutting-edge surgeries based on cell transplantation are available to repair damaged
cartilage, failure rates are high. This is largely due to a lack of suitable scaffold materials that
encapsulate transplanted cells and promote cartilage repair by mimicking healthy cartilage.
Developing scaffolds from nanofibrils, assembled from short peptides, combined with stem
cells is a promising innovation that has the potential to improve patient outcomes. However,
a number of fundamental knowledge gaps across length-scales from the molecular to the
macro prevent such advancement. These include a lack of understanding of:
1. How molecular structure of the peptide within the fibrils affects their nanoscale
morphology.
2. How nanoscale morphology affects the macroscale mechanical properties of the
scaffolds.
Without this fundamental knowledge the ability to transfer these scaffold technologies from
the lab to the clinic will be severely limited and patient outcomes will remain poor.
The projects offered will be based around answering the three questions presented above

and will use an innovative combination state-of-the-art analytical tools to understand the
molecular structures of peptide nanofibril scaffolds and correlate this with nano-
architectures, mechanical properties of the scaffolds.
Projects can be tailored based on the expertise and preference of the candidate and could
include various combinations of:
• Atomic Force Microscopy
• X-Ray Scattering (at the Australian Synchrotron)
• Modelling/Data Analysis
• Rheological Testing
• Electron Microscopy
• Circular Dichroism
Peptide Fibrils are Biomimetic of collagen a,b)

AFM Images of Phe rich fibrils c,d) Images of
collagen fibrils found in cartilage (note the
similar band structures in b and d).

Associate Professor Helena RICHARDSON
TISSUE ARCHITECTURE & COOPERATIVE
TUMOURIGENESIS
Phone: 9479 2399 E-mail: h.richardson@latrobe.edu.au
LIMS theme: Cancer
Co-Supervisor: Dr Marta Portela

Our lab uses sophisticated genetic and cell biological analysis of the vinegar fly, Drosophila,
model, to address the fundamental questions of how cell shape regulators control signalling
pathways, cell proliferation, survival and differentiation, and how their deregulation leads to
cancer in epithelial tissues. We are also interested in the interaction of the tumour with the
surrounding normal cells (the tumour microenvironment), how the innate immune system
interacts with the mutant tissue in either eliminating the mutant cells or promoting
tumourigenesis.
The regulation of tissue architecture and growth:
The correct structure of epithelial tissues (including the skin, and linings of internal organs,
such as the ducts of the mammary gland, prostate gland and pancreas) is critical for cell
function. The structure of cells in these epithelial layers is regulated by the evolutionarily
conserved apico-basal cell polarity
complexes, the Scrib, Par and Crumbs
modules. These complexes act in a
mutually antagonistic manner to define
apical and basal-lateral membrane
domains and position the adherens
junction (AJ) and tight junction (TJ),
which are important for cell-cell adhesion
and communication. Mutants in the Scrib
module (comprised of Scrib (Scribble),
Dlg (Discs-large) and Lgl (Lethal-giant-
larvae) were original discovered in
Drosophila as neoplastic tumour

suppressor genes, which regulate tissue architecture and growth. We have discovered that
mutants of Scrib, Dlg or Lgl affect cell proliferation and survival by modulating signalling
pathways. Lgl regulates the Hippo negative tissue growth pathway by controlling the
localisation of the pathway components, Hpo and Rassf, and also regulates Notch signalling
by affecting the acidification of endoctyic vesicles, which is required for -secretase-mediated
activation of Notch (S3 cleavage) (Figure 1). By contrast, Scrib and Dlg control Ras-MAPK
signalling. In order to investigate how Scrib and Dlg control cell polarity and signalling we
are collaborating with Drs Marc Kvansakul (LIMS) and Patrick Humbert (LIMS) to investigate
the Scrib protein network using biochemical and genetic approaches.
Figure 1 – Regulation of the Hippo and Notch pathways by Lgl
Cooperative tumourigenesis: When Scrib, Dlg or Lgl are mutated in patches (clones) of
cells within Drosophila epithelial tissues, despite increased proliferation, they do not
overgrow as cells at the clonal borders are removed by apoptosis mediated by recruitment
of innate immune response macrophage-like cells (hemocytes) and induction of the TNF-
JNK stress response pathway, a process termed “cell-competition”. Various signalling
pathways are involved in initiating cell competition but precisely how this occurs in scrib, dlg
or lgl mutant tissue is unclear. When an oncogene, such as RasV12, is co-expressed in
scrib, dlg or lgl mutant cells, apoptosis is blocked and massive invasive tumours (marked by
green fluorescent protein, GFP) are induced. In this context, the innate immune response
acts to promote tumourigenesis. In collaboration with Drs Marc Kvansakul (LIMS) and Patrick
Humbert (LIMS) we are using this cooperative tumourigenesis model to screen drug
libraries to identify novel bioavailable, tumour-specific anticancer compounds and
investigate their mode of action.
Moreover, in order to understand the
mechanism of tumourigenesis, we
have undertaken loss- or gain-of-
function genetic screens to identify
novel genes that act similarly to
mutants in the scrib module to
promote RasV12-driven
tumourigenesis (Figure 2). Amongst
the genes identified as contributing to
tumourigenesis in these screens,
were those involved in actin cytoskeleton, signalling, protein trafficking, metabolism, and
epigenetic regulation. We now seek to investigate the mechanism by which these
genes promote tumourigenesis and how they are involved in the function of the Scrib
module.
Figure 2 – An example of a gene that acts as tumour suppressors in cooperation with
RasV12, identified in our genetic screen
Project 1: How cell polarity regulators affect signalling pathways

The project will investigate the question of how Lgl affects the Notch and Hippo signalling
pathways in Drosophila. From our Mass Spec analysis of Drosophila Lgl protein interactors,

several endocytosis regulators have been identified. This project will investigate the
importance of these proteins in Lgl’s regulation of these signalling pathways, by utilising in
vitro physical interaction and in vivo genetic-cell biology approaches.
Project 2: The role of novel tumour suppressors in Ras-driven tumourigenesis
This project extends from our genetic screen for novel tumour suppressors that cooperate
with RasV12 to promote invasive overgrowth of neural-epithelial tissue. It will utilise
sophisticated Drosophila genetics and molecular, cell biology and biochemical approaches
to determine how one of these novel tumour suppressors affects the hallmarks of cancer in
Drosophila. The project will include analysis of how the tumour suppressor affects signalling
pathways, cell proliferation, apoptosis, differentiation and recruitment of the cellular innate
immune response, and whether it genetically and physically interacts with the Scrib module.
Both projects will suit those who enjoy working on genetically-tractable model organisms
and are interested in a holistic understanding of cancer. These projects will encompass a
wide range of cell biology (microscopy), biochemistry, genetics and molecular biology
techniques.

Dr Tatiana SOARES DA COSTA
ANTIBIOTIC & HERBICIDE DISCOVERY
Phone: 9479 2227
E-mail: t.soaresdacosta@latrobe.edu.au
LIMS theme: Molecular Design
Overview of research: The overall focus of our laboratory is to examine the structure,
function and regulation of essential proteins in bacteria and plants to guide the development
of new classes of antibiotics and herbicides, respectively.
Project 1: Repurposing antibacterials as herbicides to tackle resistance

Given the increasing rate of herbicide resistance worldwide there is an urgent need to
validate novel herbicide targets and identify new herbicide leads. The aim of this project is
to repurpose compounds known to inhibit essential enzymes that are conserved across
bacterial and plant kingdoms as herbicides. To achieve this plant enzymes will be expressed
and purified, before assessing the effects of compounds on enzyme activity using kinetic
assays and in plants using pre- and post-emergence growth assays. X-ray crystallography
will be employed to aid the rational design of herbicide candidates with improved potency
and specificity.
Project 2: Finding the Achilles Heel in multi-drug resistant bacteria

This project focuses on characterising the properties of a series of new antibiotic candidates
as individual and combinatorial treatments. Specifically, the project involves (i) determining
the minimum inhibitory concentrations of compounds against drug sensitive and drug
resistant pathogens, (ii) examining the mode of action using time-kill assays, (iii) assessing
their toxicity in mammalian cells and in vivo models, (iv) determining effects on biofilm
formation and disruption, and (iv) defining the potential and frequency for resistance to
emerge.
The projects in our laboratory encompass a wide range of biochemistry, biophysics,

microbiology and/or plant biology techniques, including recombinant protein expression and
purification, enzymology, analytical ultracentrifugation, circular dichroism spectroscopy,

microscale thermophoresis, structural biology, surface plasmon resonance, in silico docking,
rational drug design, plant growth, and bacteriology assays

Dr Lakshmi WIJEYEWICKREMA
PROTEASES AND PROTEASE INHIBITORS:
RELATIONSHIP TO DISEASE STATES
Office: LIMS1, Room 513
Phone: 03 9479 2156
E-mail: l.wijeyewickrema@latrobe.edu.au
Controlled proteolysis is one of the major pathways by which the estimated 1-1.5 million
peptides and proteins needed to fulfil the complexity of human life are produced from
~26,000 human genes. The activity of proteases is ubiquitous and of exceptional
importance. For example, proteases control pathways that govern whether a cell lives or
dies (apoptosis). Other examples of the involvement of proteases in “life and death”
processes include important roles for these enzymes in neural, endocrine and
cardiovascular signalling, digestion, degrading misfolded or unwanted proteins, immunity
and cell division events. The importance of the activity of proteases is also apparent in
numerous human pathological conditions related to alterations in protease activity levels,
including cancer, arthritis, inflammation, neurodegenerative and cardiovascular diseases.
The Wijeyewickrema laboratory is interested in characterising proteases and how these
molecules function as pathogenic agents in bacteria and parasites, as well as how these
same molecules and their inhibitors and receptors are used by the host system to defend
against pathogens. The lab has a strong research focus on the complement system, which
uses proteases within a cascade of events to target pathogens and alert the immune system
to their presence. We use techniques in protein biochemistry, molecular biology, biophysics
and X-ray crystallography, to produce and analyse our proteins of interest. We use this
information to understand the intricate control mechanisms that are built into the various
molecules and how these affect their activity.
Honours Project:
Cell surface-anchored serine protease, TMPRSS2: a potential target for understanding
coronavirus infectivity and spread.
Project Description
The genomic RNA of coronaviruses such as SARS-CoV-2 is surrounded by an envelope

composed of a lipid bilayer and envelope proteins. SARS-CoV-2 initiates human cell entry
after the Spike protein (S protein) present on the envelope binds to a cell membrane receptor
ACE2. The S protein is cleaved into S1 and S2 by a human cell-derived protease (proteolytic
enzyme) that is assumed to be Furin. S1 then binds to its receptor, ACE2. The other
fragment, S2, is cleaved by TMPRSS2, a human cell surface serine protease, resulting in
membrane fusion. According to recent studies ACE2 and TMPRSS2 are essential in airway
cells for SARS-CoV-2 infection.
These studies have identified TMPRSS2 as an essential host cell factor for these respiratory
viruses and further demonstrated that inhibition of virus activating host cell proteases,
particularly TMPRSS2, provides a promising approach for the development of therapeutics
to treat respiratory virus infections.
Our team has extensive expertise in the study of enzymes used by pathogens to attack the
host and their interaction with the immune system. We will use our cross-disciplinary
expertise to examine the protein structure, and protease specificity of TMPRSS2 as a means
to reveal ways to indirectly and directly inhibit its function. We will then use this knowledge
to guide the development of inhibitors that block the biological function of TMPRSS2. We
anticipate that this work will provide mechanistic insights into precisely how TMPRSS2 acts
as a host factor that is essential for the infectivity of SARS-CoV-2. The specific aims of this
study are to:
1. Express a version of TMPRSS2 constructed using recombinant DNA techniques and
purify the enzyme;
2. Carry out an initial analysis of the peptide substrate cleavage profile of TMPRSS2
using the REPLi peptide substrate library,
Techniques:
Cloning/mutagenesis, Plasmid isolation/purification, Protein expression/purification,
Enzyme assays.

Olivia Newton-John Cancer Research Institute

Level 5, Olivia Newton-John Cancer & Wellness Centre (ONJCWC)
145 Studley Road, Heidelberg, VIC 3084
www.onjcri.org.au
The Olivia Newton-John Cancer Research Institute (ONJCRI) at the Austin Hospital in
Heidelberg is an independent medical research institute with strong collaborative links to
LIMS. Honours projects in Biochemistry, Genetics or Biomedical science may be carried out
within some ONJCRI laboratories as part of the LIMS program. In addition to meeting the
attendance, training and assessment requirements of the LIMS program, students
completing projects in ONJCRI laboratories will also be required to undergo safety training
at the Institute, and where appropriate, animal handling training.
The ONJCRI is Australia’s newest Cancer Research Institute, established to be a world
leader in research and discovery regarding cancer, its origins, and developing new
treatments for the care of people affected by cancer.
The Institute occupies three floors of state-of-the-art laboratories at the Olivia Newton-John
Cancer and Wellness Centre (pictured) and is the successor to the internationally renowned
Ludwig Institute for Cancer Research that established a collaborative clinical research
programme with Austin Health in 1990. Embedded within the comprehensive cancer
centre, the Institute is uniquely placed to bring together basic and translational cancer
research in a co-ordinated and successful manner.
The Institute entered into a
research collaboration
agreement with La Trobe
University in 2014, which led to
the creation of the School of
Cancer Medicine. The
relationship fosters collaborative
research and the joint training
and scholarship support of
research students enrolled at
the University. Professor
Matthias Ernst is the Head of
School of Cancer Medicine, and
Director, Olivia Newton-John
Cancer Research Institute.

With a strong track record in attracting
grant support from Australian and
International sources and successful
industry collaborations, our research
teams are currently investigating
melanoma, lung, breast, brain and
gastrointestinal tumours. All research
activities are enhanced and supported
by outstanding platform technologies,
infrastructure, facilities, and technical
expertise including:
• ACRF Centre for Translational Cancer Therapeutics and Imaging

• Cell biology
• Mammalian Protein Expression and Purification Facility
• Protein chemistry
• Bioresource Facility
• Therapeutic modelling
• Flow cytometry and cell sorting
• Cell line repository and tissue banking
• Genomics including molecular pathology
• Radiochemistry and PET Solid Targetry
• Next generation sequencing and digital PCR
• Clinical trials centre to facilitate the clinical translation of laboratory discoveries.
The Institute invites applications from highly motivated and creative individuals to undertake
PhD, and BSc (Hons), degrees. Students will enrol in the School of Cancer Medicine. The
Institute attracts students from a wide range of disciplines biochemistry, genetics,
immunology, medicine, microbiology, pathology and physiology. The Institute maintains a
rigorous student mentoring and support program which has contributed to the Institute’s
outstanding track record of student success.
We are committed to providing post-graduate students with an environment in which to excel
in cancer research and make original discoveries that will improve the understanding and
treatment of cancer. The Institute provides state-of-the-art facilities and world-class
scientists and medical specialists to guide young researchers.

Dr Michael BUCHERT
TUMOUR MICROENVIRONMENT AND
CANCER SIGNALING GROUP
Office: ONJCRI, Level 5, Austin Health Campus, Heidelberg
Phone: 9496 5491
E-mail: michael.buchert@onjcri.org.au
LIMS theme: Cancer
Persistent inflammation is a cancer promoting condition and a better understanding of its

underlying mechanisms is key to developing better strategies to curb its chronic nature and
decrease the incidence of progression to metaplasia and cancer.
In this project we will study the role of epithelial tuft cells – rare, solitary, chemosensory cells
found in most epithelial tissues associated with mucosal surfaces such as the lung, intestine
and stomach. Our understanding of tuft cell biology is still in its infancy but emerging
literature has demonstrated a key role for this cell type in maintaining tissue homeostasis
and in the host’s immune defence against parasite infections and allergens. Our lab has
generated ample data suggesting that tuft cells are also playing an important part in the early
stages of tissue metaplasia and tumour formation. This honours project will therefore extend
upon these observations by genetically and pharmaceutically manipulating the tuft cell
population in the gastrointestinal tissues (stomach, large and small intestine) under normal
and chronic inflammatory conditions using sophisticated models.
Among the different experimental techniques this project offers are: tissue dissections and
tissue harvest, FACS analysis, confocal and multiphoton microscopy, tissue purification of
total RNA and protein, cDNA conversion of total RNA, real-time qPCR, Western blotting,
immunohistochemistry, tissue culture of mammalian cells, transfection of mammalian cells,
organoid cultures and immunostaining of gastric organoids.
The Buchert lab is at the Olivia Newton-John Cancer Research Institute located on the
Austin Health campus in Heidelberg. His lab currently consists of two PhD students, one
junior postdoc and a senior research associate.

Dr ASHWINI CHAND
CANCER THERAPEUTICS DEVELOPMENT
Office: Level 5, ONJ Centre, 145 Studley Road, Heidelberg Vic 3084
Australia
Phone: 9496 9140
E-mail: ashwini.chand@onjcri.org.au ; sarah.bennett@onjcri.org.au
LIMS theme: Cancer
Co-supervisor: Dr Sarah Bennett
The role of IL-11 in triple negative breast cancer

Diagnoses of triple negative breast cancer (TNBC) account for ~15-20% of all breast cancers
and is often associated with metastasis and poor patient survival outcomes. It is
characterised by an absence of the Estrogen Receptor (ER) and Progesterone Receptor
(PR) and no amplification of the HER2 receptor. This renders TNBC insensitive to hormone-
directed therapies and limited treatment options exist beyond cytotoxic chemotherapy, which
has a high rate of early relapse. Therefore, there is an urgent need to develop a better
understanding of the molecular drivers of TNBC in order to develop more treatment options.
Our previous work has identified Interleukin 11 (IL-11), a member of the IL-6 family of
cytokines, as a potential driver of TNBC progression and metastasis. An analysis of publicly
available datasets reveals IL-11 levels are positively correlated with disease progression
and metastatic spread to the bone. To mediate protumourigenic signalling, IL-11 complexes
with its receptor (IL-11RA) and the co-receptor, gp130 to phosphorylate the Signal
Transducer and Activator of Transcription 3 (STAT3). Activation of STAT3 in the cancers
drives cancer hallmarks including proliferation, cell survival, angiogenesis and metastasis.
This project will focus on understanding cytokine-dependent pathways in breast cancer
progression and metastasis. We have generated human TNBC cell lines lacking IL-11 and
IL-11RA expression using CRISPR-Cas9 directed knockdown. The aim of this honours
project will be to characterise these cell lines as follows:
1. Determine binding of the downstream signal transducer STAT3 to target genes which
induce proliferation and metastasis using ChIP-seq analysis.
2. Validate the expression of target genes at the mRNA (qPCR) and protein (western blot)
level.

3. Functionally determine the effect of IL-11 and IL-11RA knockdown in vitro using
proliferation, migration and invasion assays.
The student taking on this project will gain an understanding of the underlying concepts of
cancer biology. They will be exposed to a large range of molecular biology techniques (listed
above), which are broadly applicable to cancer biology. The results of this study will
contribute directly to the development of targeted therapies to improve outcomes for TNBC
patients.
The work at ONJCRI/La Trobe School of Cancer Medicine will take place in laboratory
setting that has access to patient material and focuses on clinically relevant aspects in the
treatment of cancer patients.

Professor Matthias ERNST
TUMOUR MICROENVIRONMENT AND
CANCER SIGNALLING
Office: Level 5, ONJCWC, Austin Health, Heidelberg
Phone: 9496 9775
E-mail: matthias.ernst@onjcri.org.au,
amr.allam@onjcri.org.au ashleigh.poh@onjcri.org.au
LIMS theme: Cancer
Positions available: Two (one for each project)
Project 1: Co-Supervisor: Dr Amr Allam

Targeting STAT3 in CAFs to improve immunotherapies in advanced colon cancer.
The tumour microenvironment plays an integral role in promoting tumour progression
and triggering the onset of metastasis. Remodeling of the tumour microenvironment is
regulated via complex cross-talk between tumour cells and the host’s resident stromal
cells that comprise the tumour microenvironment (TME). Cancer-associated fibroblasts
(CAFs) are stromal cells, which play a pivotal role in remodeling the TME to promote
tumour development and enable tumour cells to evade immune responses. Recently, the
cancer stemness protein, STAT3 was reported to be involved in regulating CAFs’ activities
in remodeling the extra cellular matrix, which correlated with elevated tumour burden in
animal models and poor prognosis in patient cohorts.
Investigating the immune

landscape in TME using
multiplex imaging system.
Top left image, represents

tumour biopsy of colorectal
cancer patient. Multiplex
imaging panel was used to
identify infilterating immune
cells populations (Tcells
(CD3),denderetic cells
(CD11c), inflammatory
marcophages (CD163),
monocytes (CD14)) in different
areas of the tumour (zoomed
images). Scale bar 2 mm.
This project will take advantage of our genetically modified mouse models for STAT3

signaling and state-of-art imaging platform to investigate how STAT3 affects the cross-
talk between CAFs and tumour cells within the TME of colon cancer. We will investigate
the extent to which this cross-talk not only remodels the tumour microenvironment but
also promote evasion of anti-tumour immune responses and limits the efficacy of current
immunotherapies. This functional insight will be correlated with findings in a recent trial
with human colon cancer patients and combining STAT3 inhibition with immunotherapies.
Students will work in state-of-the-art research labs at the School of Cancer Medicine
/Olivia Newton-John Cancer Research Institute, which is embedded in the ONJ Cancer
Centre. Students will gain experience in multidisciplinary techniques in tumour biology,
immunology, molecular biology, advanced microscopy (multi-photon) and pre-clinical
mouse models.
Project 2: Co-Supervisor: Dr Ashleigh Poh

Reshaping the immunosuppressive tumour microenvironment of brain cancer
Glioblastoma (GBM) is the most common and fatal type of primary malignant brain cancer.
A hallmark of GBM is an immunologically “cold” tumour microenvironment characterised
by an abundance of immunosuppressive myeloid cells, which limit anti-tumour immune
responses. Thus, readily translatable strategies that can reprogram the
immunosuppressive tumour microenvironment and promote the recruitment and activation
of cytotoxic immune cells represent a major advancement for the treatment of GBM.
Elevated expression of the myeloid-specific kinase Haematopoietic Cell Kinase (HCK) is

observed in most solid cancers and correlates with poor patient survival. We have previously
shown that constitutive HCK activation promotes tumour growth and progression by
facilitating the polarisation of myeloid cells towards an immunosuppressive endotype
(Poh et. A; Cancer Cell 2017, Cancer Immunology Research 2020). Accordingly, genetic
ablation or pharmacologic inhibition of HCK impairs colon and gastric tumour growth by
reducing the abundance of immunosuppressive myeloid cells.
Given the role of HCK signaling in myeloid-driven immunosuppression, and the

contribution of these cells in GBM, we hypothesise that targeting HCK will present new
opportunities for the treatment of brain cancer.
The overall aims of this project are to:

• Dissect the immunological mechanisms by which constitutive HCK activation or loss of
HCK signaling influences GBM development and progression
• Validate the therapeutic efficacy of novel HCK-specific small molecule inhibitors in pre-
clinical models of GBM
Students will work in state-of-the-art research laboratories of the School of Cancer

Medicine /Olivia Newton-John Cancer Research Institute, which is embedded in the ONJ
Cancer Centre. Students will gain experience in multidisciplinary techniques in tumour
biology, immunology, molecular biology, and pre-clinical mouse models.

Dr Erinna LEE & Associate Professor Doug FAIRLIE
CELL DEATH AND SURVIVAL
Office: Level 4 ONJCWC, Austin Health, Heidelberg
Phone: 9496 9369
E-mail: erinna.lee@onjcri.org.au, doug.fairlie@onjcri.org.au
LIMS theme: Cancer
Background
Cells possess distinct pathways that promote their survival or death. These pathways are
tightly regulated but when this regulation goes awry, diseases such as cancer ensue. Our
lab is interested in two main pathways that control cell death and cell survival. These are
apoptosis and autophagy respectively.
Apoptosis is a form of cell death required for the removal of damaged or unwanted cells. We
are primarily interested in the mechanisms by which the BCL-2 family of proteins regulate
this process and how they can be targeted with drugs for disease treatment.
Autophagy is one mechanism of cell survival and is an evolutionarily conserved process of

cellular self-cannibalism. Damaged or unnecessary cellular components are targeted to the
lysosome for their removal once encapsulated in autophagic vesicles. A large focus of our
work is on the autophagy inducer Beclin1 and how it contributes to cellular homeostasis and
disease.
Project Description
Broadly, the Honours project(s) will be aimed at understanding the molecular mechanisms
by which apoptosis and/or autophagy are regulated by our proteins of interest under normal
physiological conditions and how this can go awry to give rise to disease. We are also
interested in exploring the therapeutic value of molecules that modulate these pathways and
developing new ways in which we can target these pathways for therapeutic benefit in cancer
treatment.
Upon completion of the Honours year we expect our student to be equipped with
fundamental laboratory techniques in cell biology, protein biochemistry and drug screening.
Skills that will be essential for a future career as a lab scientist.

Professor John MARIADASON
ONCOGENIC TRANSCRIPTION
Office: Level 5 ONJCRI, Austin Hospital, Heidelberg
Phone: 9496 3068
E-mail: j.mariadason@latrobe.edu.au, john.mariadason@onjcri.org.au
LIMS theme: Cancer
Co-supervisor: Dr. Ian Luk
Role of the EHF transcription factor in breast cancer
EHF is a transcription factor that is highly expressed in the breast epithelium. We recently
generated an Ehf knockout mouse and found that female mice are unable to feed their pups.
Examination of the mammary glands of Ehf KO mice revealed a pronounced defect in the
development of this tissue during pregnancy. Expression of EHF is also downregulated in
human breast cancers, particularly the triple negative subtype, where tumours with low EHF
expression have a poorer outcome. Triple negative breast cancers (TNBC’s) comprise ~20%
of all breast cancers and have limited treatment options. There is therefore an urgent need
to identify the driver genes which give rise of this subtype so that new treatments can be
developed.
Project outline
The goal of this Honours project is to determine the role of EHF in the growth, survival,
migration and chemotherapy response in triple negative breast cancer cells. We will achieve
this as follows:
1. Determine the level of EHF mRNA and protein expression in 20 breast cancer cell lines,
including 5 TNBC cell lines.
2. Determine the effect of EHF re-expression on cell proliferation, survival, migration and
response to chemotherapy in TNBC cells.
3. Determine the effect of EHF knockdown in TNBC cells which express EHF on cell
proliferation, survival, migration and response to chemotherapy.
4. Identify the target genes of EHF in TNBC cells following EHF knockdown or
overexpression.

The student undertaking this project will learn the fundamental concepts of cancer biology
and use a variety of techniques including working with cell line models of breast cancer,
western blotting, immunohistochemistry, transfections and assessing response to drug
treatment.

Dr Delphine MERINO & Dr Jean BERTHELET
TUMOUR PROGRESSION AND
HETEROGENEITY LABORATORY
Office: Olivia Newton-John Cancer Research Institute
Phone: +61 3 9496 9368
E-mail: delphine.merino@onjcri.org.au
LIMS theme: Cancer
Studying the molecular characteristics of metastatic clones
Project Description
Breast cancer is a highly heterogeneous disease. Many studies have shown that patient
tumours are composed of a large number of cells or group of cells called ‘clones’ that are
genetically diverse. This high level of heterogeneity represents a major obstacle for cancer
therapy, some of these cells may have a survival advantage to colonise vital organs and
resistant standard treatments, leading to disease recurrence.
To colonise distant organs, tumour cells must intravasate into blood vessels as circulating
tumour cells, extravasate and survive in their new micro-environment. One of our previous
studies showed that only a minor proportion of cells present in the primary tumour will survive
and form lethal metastases. Breast cancers are known to preferentially colonise lungs,
bones, lymph nodes, liver, brain and ovaries, and how the microenvironments of these
different organs impact on clonal selection remains unclear.
Our laboratory aims at understanding the biologic properties of metastatic clones. We would
like to understand how they differ between different metastatic sites and resist current
treatments. Therefore, we are using patient samples, cell lines and a new technology called
‘cellular barcoding’ to label cancer cells from patient samples and follow their behaviour.
Using sequencing at bulk or single cell level we are planning to identify the pathways
involved in metastatic spread and drug resistance, to ultimately propose better treatments
for patients with breast cancer.

Dr Lisa MIELKE
MUCOSAL IMMUNITY & CANCER
Office: Olivia Newton-John Cancer Research Institute
Level 5, ONJ Centre, 145 Studley Road, Heidelberg
Phone: 9496 9126
E-mail: lisa.mielke@onjcri.org.au
Modulation of the immune system has revolutionised the treatment of some cancer types,
such as melanoma, non-small cell lung cancer and renal cancer. Despite its huge success,
immunotherapy with drugs blocking immune inhibitory receptors PD-1 and CTLA4, fails in
gastric and colon cancer. Immunotherapy in cancer patients also results in severe side
effects in a significant proportion of patients due to systemic activation of the immune
system, causing autoimmune-like syndromes. The Mucosal Immunology and Cancer
Laboratory focuses on identifying new immune targets that can be explored to develop
novel therapeutics to treat stomach and colon-specific cancers, while avoiding side effects.
We use mouse models and patient samples to understand the organ-specific functions of
intraepithelial lymphocytes (IELs), that consists of heterogeneous populations of T cells that
are distinct in their frequency and function across different organs of the gastrointestinal tract
(GI). Our preliminary studies have shown that one population, known as gamma delta T
cells, plays a protective role in colon cancer. In this project we will use single-cell RNA
sequencing, flow cytometry and multiplexed fluorescent immunohistochemistry technologies
to understand the function of gamma delta T cells in mouse models of colon and stomach
cancer and patient samples.
Techniques employed will include:

• Tissue harvest from mice.
• Tissue digestion and extraction of immune cells from mouse GI tract
• Immunohistochemistry of mouse and human samples
• Microscopy
• Flow cytometry
• Mouse handling

Dr Bhupinder PAL
CANCER AND SINGLE CELL BIOLOGY LABORATORY
TRANSLATIONAL BREAST CANCER PROGRAM
Office: School of Cancer Medicine, Level 4 ONJCWC, Austin Health,
Heidelberg
Phone: 9496 9368 / 9496 5366
E-mail: bhupinder.pal@onjcri.org.au
LIMS theme: Cancer
Understanding metastatic breast cancer by single cell transcriptomics
Metastatic breast cancer refers to a disease that has spread beyond the breast and regional
lymph nodes to distant sites, with variable locations and volumes of organ involvement.
Targeting metastatic breast cancer cells is proving difficult due to the molecular
heterogeneity that arise from different factors including the cell of origin, somatic mutations
in breast cancer susceptibility genes, and genetic alterations including mutations, deletions,
fusions or amplifications of key genes. Cancer cells that escape and seed at new sites
usually undergo molecular changes in their genetic and epigenetic landscape. Furthermore,
the tumour microenvironment can also influence cancer cell survival, treatment outcome and
cancer metastasis.
The technological advancements in the field of

single cell biology has allowed the study of
molecular heterogeneity in mixed cell
populations and shed light on cell lineage
relationships. Our work has revealed variable
heterogeneity in breast cancer cells and
identified novel cell clusters in breast tissue.
The primary objective of this project is to gain novel molecular insights into aggressive and
drug resistant breast cancers. We will use high-throughput single cell
transcriptomic/genomic analysis approach to study clinical samples from breast cancer
patients undergoing treatment. Expected outcome: 1) Understand the role of tumour cell
heterogeneity in promoting cancer disease. 2) identify specific immune/stromal gene
signatures that can predict metastatic resurgence. 3) discover biomarkers associated with
metastatic progression. Novel biomarkers will be evaluated utilising breast cancer patient
derived xenografts and organoid assays.

Dr Normand POULIOT
BREAST CANCER METASTASIS
Office: Translational Breast Cancer Program, Level 4 ONJCRI, Austin
Health, Heidelberg
Phone: 9496 9668
E-mail: normand.pouliot@onjcri.org.au
LIMS theme: Cancer
Positions available: Two (one for each project)
Co-supervisor: Dr Delphine Denoyer
Pre-clinical research in the Matrix Microenvironment & Metastasis Lab seeks to understand
how bi-directional interactions between breast cancer cells and the surrounding
microenvironment influence metastatic progression and response to therapy. We are
particularly interested in the role of matrix proteins and cell adhesion receptors in facilitating
the spread of aggressive breast cancer subtypes (HER2+ve and Triple Negative) to brain
and other organs.
Project 1: Limitrin: a new cell adhesion receptor regulating breast cancer metastasis
Adhesion of cancer cells to the surrounding matrix and endothelium is critical for successful
metastasis. This project seeks to characterise the expression and function of a novel cell
adhesion receptor called limitrin/DICAM, in breast cancer metastasis. Limitrin has been
shown to mediate cell-cell adhesion in normal epithelial and endothelial cells but its role in
cancer remains unknown. We have found that the expression of limitrin is increased in breast
cancer cell lines and tumours that spread (metastasise) to the brain. Preliminary results in
various breast cancer models indicate that limitrin may promote cancer cell adhesion to, and
migration through, the endothelium thereby facilitating colonisation of the brain.
The project will test the hypothesis that suppressing the expression of limitrin will prevent or
delay the outgrowth of brain metastases in clinically relevant mouse models of breast cancer
brain metastasis. The project will involve knocking out limitrin in mammary carcinoma lines
using CRISPR/Cas9 technology and validation of knockout by flow cytometry, RT-PCR,
immunofluorescence and immunohistochemistry. The effect of limitrin suppression on
cellular functions will be assessed in in vitro proliferation, adhesion, migration, invasion and
trans-endothelial migration assays. The relationship between limitrin and metastasis will be
addressed in vivo using preclinical models of breast cancer brain metastasis.

Project 2: Evaluating the efficacy and mechanism of action of tyrosine kinase inhibitors in
triple negative breast cancer
HER2+ve and triple negative breast cancer (TNBC) are aggressive subtypes of breast
cancer that have a high propensity to spread (metastasise) to the brain. Antibody-based
therapies for breast cancer effectively control systemic disease and extend life in some
patients but are largely ineffective against brain metastases due to the poor permeability of
antibodies across the blood-brain barrier and/or acquired resistance that almost inevitably
develops. Small molecule tyrosine kinase inhibitors (TKIs) provide a promising alternative to
antibody due to their high potency, small size and greater brain permeability. We have
evaluated the efficacy of multiple TKIs in pre-clinical mouse models of HER2+ve breast
cancer brain metastasis and identified neratinib as a potent inhibitor with a unique
mechanism of action called ferroptosis, a process distinct from apoptosis. We are currently
testing new combination therapies to overcome resistance to neratinib in vitro and in vivo.
This project seeks to extend these findings to TNBC by comparing the efficacy of various
TKIs alone or in combination with cell adhesion receptor inhibitors in vitro. Whether neratinib
inhibits TNBC growth through ferroptosis or other cell death pathways will be investigated in
standard in vitro assays. The efficacy of neratinib mono and combination therapies will be
evaluated in mouse models of TNBC metastasis. The project will make use of a variety of
techniques including standard cell culture, proliferation assays, metabolic assays, western
blotting, flow cytometry, immunohistochemistry, qPCR and animal models.

RANKED ENTRY PROJECT SELECTION FORM
Name: ……………………………………………………………………………………………………
Email: ……………………………………………………………………………………………………
Mobile: ……………………………………………………………………………………………………
Ranked entry: Rank the laboratories you are interested in joining, from most preferred (1) to least preferred
(up to 20) in the table below.
Supervisor (Department) Page Preference

Biochemistry and Genetics:
Michael Foley 8
David Greening 10
Begona Heras 12
Mark Hulett 14
Patrick Humbert 16
Marc Kvansakul 18
Suresh Mathivanan 20
Robyn Murphy 22
Jacqueline Orian 24
Hamsa Puthalakath 26
Nick Reynolds 28
Helena Richardson 30
Tatiana Soares da Costa 33
Lakshmi Wijeyewickrema 35
ONJCRI/Cancer Medicine:
Michael Buchert 39
Ashwini Chand 40
Matthias Ernst 42
Erinna Lee / Doung Fairlie 44
John Mariadason 46
Dr Delphine Merino & Dr Jean Berthelet 47
Lisa Mielke 48
Bhupinder Pal 49
Normand Pouliot 50
Please email the completed form by 5pm Friday 6th November 2020 to i.poon@latrobe.edu.au
If you wish to withdraw your application, please notify i.poon@latrobe.edu.au

2021 HONOURS RESEARCH PROJECTS
DEPARTMENT OF BIOCHEMISTRY & GENETICS
HONOURS COORDINATOR
Dr Ivan Poon
Associate Professor
Phone: 9479 6488
E-mail: I.Poon@latrobe.edu.au

General enquiries
La Trobe University
School of Molecular Sciences
Bundoora VIC 3086
Australia
T +61 3 9479 2160
F +61 3 9479 1266
E LIMSEnquiries@latrobe.edu.au
latrobe.edu.au/lims

2021 Biochem and Genetics Honours Projects

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2021 Biochem and Genetics Honours Projects

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2021 Honours

School of Molecular Sciences/

COURSE STRUCTURE .............................................................................................. 4

PROJECT ALLOCATION PROCESS ............................................................................. 5

THE DEPARTMENT OF BIOCHEMISTRY & GENETICS................................................. 6

OLIVIA NEWTON-JOHN CANCER RESEARCH INSTITUTE ......................................... 37

RANKED ENTRY PROJECT SELECTION FORM ......................................................... 53

BIOCHEMISTRY & GENETICS Page | 1

Skills you will learn

Past student testimonials

BIOCHEMISTRY & GENETICS Page | 3

Choosing an Honours Project

BIOCHEMISTRY & GENETICS Page | 4

To organise an Honours research project and supervisor:

BIOCHEMISTRY & GENETICS Page | 5

The Department of Biochemistry and Genetics contains 27 research laboratories, teaching

BIOCHEMISTRY & GENETICS Page | 6

• Confocal and widefield microscopy (for imaging fluorescently labelled biomolecules in

BIOCHEMISTRY & GENETICS Page | 7

Subjects prerequisites: MED3LAB and/or MED3PRJ

LIMS theme: Infection and Immunity

Positions available: One

BIOCHEMISTRY & GENETICS Page | 8

Wynn T, J Exp Med 2011

BIOCHEMISTRY & GENETICS Page | 9

MOLECULAR PROTEOMICS GROUP

Subjects prerequisites: MED3LAB, MED3PRJ or GEN3LAB

LIMS theme: Cancer, Nanoscience

Positions available: One

The Molecular Proteomics laboratory is focused on understanding the molecular

Understanding the roles of extracellular vesicles during cardiac fibrosis

BIOCHEMISTRY & GENETICS Page | 10

BIOCHEMISTRY & GENETICS Page | 11

Subjects prerequisites: MED3LAB and/or MED3PRJ

LIMS theme: Infection & Immunity

Positions available: One

Disarming bacteria: understanding the structure and function of bacterial toxins

In this project we will investigate a k e y A T s u b g r o u p ,

BIOCHEMISTRY & GENETICS Page | 12

The binding mode and potency of

BIOCHEMISTRY & GENETICS Page | 13

Subjects prerequisites: MED3LAB, MED3PRJ and/or GEN3LAB

LIMS themes: Cancer, Infection & Immunity

Positions available: One

Heparanase function in tumour progression

BIOCHEMISTRY & GENETICS Page | 14

Innate defense molecules as novel antimicrobial and anti-cancer agents

Defensins are innate immune molecules

BIOCHEMISTRY & GENETICS Page | 15

Subjects prerequisites: MED3LAB or MED3PRJ

LIMS theme: Cancer

Positions available: One

Topic 1: Cell Polarity and Cancer

BIOCHEMISTRY & GENETICS Page | 16

BIOCHEMISTRY & GENETICS Page | 17

Subjects prerequisites: MED3LAB and/or MED3PRJ

LIMS theme: Infection & Immunity

Positions available: One

Virus-mediated inhibition of programmed cell death

BIOCHEMISTRY & GENETICS Page | 18

BIOCHEMISTRY & GENETICS Page | 19

Subjects prerequisites: MED3LAB and/or MED3PRJ and/or GEN3LAB

LIMS theme: Cancer