Medicine, Nursing and Health Sciences
Honours Projects 2017
Department of Anatomy and
Developmental Biology
Front Cover Image:
Immunofluorescently labelled mouse ID8 ovarian cancer cell line detecting Hypoxia-
inducible factor 1-alpha (HIF-1; red) and dipeptidyl peptidase IV (DPP4; green).
Photo courtesy of Ms Laura Moffitt, Honours student 2016, Laboratory of Dr Andrew
Stephens and Dr Maree Bilandzic.
2016 Department of Anatomy and Developmental Biology
Honours Students
Back row (left to right): Ming Tham, Krishan Singh, Asyraaf Ahmad, Justin Crockett, Matthew Rogerson, Maria
Lambouras, Renee Kazanis, Tayla Penny, Natasha De Zoysa, Laura Moffitt, James Rule, Brad Bassett
Front row: (left to right): A/Prof Craig Smith (Convenor), Ryan Sheridan, Alexander McDonald, Nghi Tran, Natalie
Dassanayake, Robert Vary, Indya Davies, Deborah Morrison, Jordan Knight-Sadler, Merrin Pang, Anna Muccini, Tayla
Hogan, Vinay Latchman
Absent: Grace WhitBread
TABLE OF CONTENTS
INTRODUCTION ......................................................................................................................................................................................... v DEPARTMENT OF ANATOMY AND DEVELOPMENTAL BIOLOGY ................................................................................................................. vi THE MONASH BIOMEDICINE DISCOVERY INSTITUTE ................................................................................................................................. vi BDI PROGRAME: CANCER .......................................................................................................................................................................... 7
Epithelial Regeneration Laboratory .............................................................................................................................................................................. 7 Molecular regulation of intestinal stem cells ...................................................................................................................................................................... 7 Role of stem cell activity in the initiation and progression of colorectal cancer ................................................................................................................. 7 Functional Screening using intestinal organoids ................................................................................................................................................................. 8
Prostate Cancer Research Group .................................................................................................................................................................................. 9 Pre-clinical testing of novel combination therapies in mouse models of prostate cancer .................................................................................................. 9 New human models for rapid preclinical testing of prostate cancer .................................................................................................................................. 9 Defining epigenome changes in the tumour microenvironment ...................................................................................................................................... 10 Reconstructing the evolution of therapy-resistance metastatic prostate cancer ............................................................................................................. 10
BDI PROGRAME: CARDIOVASCULAR DISEASE .......................................................................................................................................... 11 Cardiovascular and Renal Developmental Programming Laboratory ........................................................................................................................... 11
Long-Term Impact of Preterm Birth on the Renal Vasculature ......................................................................................................................................... 11 Effect of postnatal steroids on the preterm kidney .......................................................................................................................................................... 11
Kidney Development, Programming and Disease Research Laboratory ....................................................................................................................... 12 In chronic kidney disease, does the degree of podocyte depletion influence the success rate of steroid treatment? ..................................................... 12 Mild podocyte depletion and its effect on the development of glomerular hypertrophy ................................................................................................ 12 Does a maternal low protein diet in mice lead to low podocyte endowment and does this render mice more susceptible to kidney disease?.............. 13
BDI PROGRAME: DEVELOPMENT AND STEM CELLS .................................................................................................................................. 14 Developmental Diseases Laboratory .......................................................................................................................................................................... 14
Understanding normal and abnormal kidney development ............................................................................................................................................. 14 Dissecting the molecular basis of congenital kidney diseases ........................................................................................................................................... 14
Male Infertility and Germ Cell Biology Laboratory ...................................................................................................................................................... 15 Microtubule severing proteins and their importance in male fertility and behaviour ...................................................................................................... 15 The function of a novel sperm tail protein in male fertility ............................................................................................................................................... 15
Neuronal Development and Plasticity Laboratory ...................................................................................................................................................... 16 How to control aggregation of toxic proteins? A conserved microRNA holds the key. ..................................................................................................... 16
Oocyte and Embryo Development Laboratory ............................................................................................................................................................ 17 Study of mitochondrial biogenesis and dynamics during oogenesis ................................................................................................................................. 17
Ovarian Biology Laboratory ....................................................................................................................................................................................... 18 Uncovering the molecular mechanisms that determine the length of the female fertile lifespan.................................................................................... 18 Characterising ovarian damage caused by anti-cancer treatment .................................................................................................................................... 18
Palaeodiet Research Lab ............................................................................................................................................................................................ 19 Dental wear development in children ............................................................................................................................................................................... 19 Functional morphology of primate teeth .......................................................................................................................................................................... 19
RNA Processing and Development Laboratory ........................................................................................................................................................ 20 RNA processing pathways in adult stem cells ................................................................................................................................................................... 20 RNA regulation during zebrafish development ................................................................................................................................................................. 20 No nonsense – gene expression control in stem cells ....................................................................................................................................................... 21
Polo Group: Reprogramming and Epigenetics ............................................................................................................................................................ 22 Understanding and exploding the reprogramming Process .............................................................................................................................................. 22
BDI PROGRAME: INFECTION AND IMMUNITY .......................................................................................................................................... 23 Stem Cells and Immune Regeneration Laboratory ...................................................................................................................................................... 23
Evaluating the functional potential of regenerated CD8 T cells in aged mice ................................................................................................................... 23 BDI PROGRAME: NEUROSCIENCE ............................................................................................................................................................. 24
Nervous System Development and Repair Laboratory ................................................................................................................................................ 24 Morphogenesis of brain size and shape ............................................................................................................................................................................ 24 Cellular and molecular mechanisms of axonal regeneration ............................................................................................................................................ 24
CENTRE FOR HUMAN ANATOMY EDUCATION .......................................................................................................................................... 25 3D Printing Laboratory .............................................................................................................................................................................................. 25
Creating a human hand for surgical simulation ................................................................................................................................................................ 25 Fogg Laboratory ........................................................................................................................................................................................................ 26
3D Quantitative morphometry of the anterior talofibular ligament: a surgical perspective ............................................................................................. 26 The ulnar ligament complex of the wrist: a modern anatomical puzzle............................................................................................................................ 26
EDUCATION FOCUSED .............................................................................................................................................................................. 27 Centre for Human Anatomy Education: Lazarus Lab .................................................................................................................................................. 27
The Impact of Online Discussion on Student Learning and Development ........................................................................................................................ 27 The Impact of Online Discussion on Student Learning and Development ........................................................................................................................ 27 The Impact of Twitter on Developing Communities of Practice and Engagement ............................................................................................................ 28
THE HUDSON INSTITUTE .......................................................................................................................................................................... 29 Sex Determination and Gonadal Development Laboratory ......................................................................................................................................... 29
Identifying novel sex determination genes responsible for DSD ....................................................................................................................................... 29 FGF signalling and sex reversal ......................................................................................................................................................................................... 30 Characterisation of novel gonadal targets of Sox9............................................................................................................................................................ 30
Brain and Gender Laboratory ..................................................................................................................................................................................... 31 How are male and female brains different? ..................................................................................................................................................................... 31 Why is SRY A Risk Factor in men with Parkinson’s disease? .............................................................................................................................................. 31 The biological basis of gender identity .............................................................................................................................................................................. 32
MAIN SUPERVISORS AND PROJECTS ........................................................................................................................................................ 33
2017 Anatomy and Developmental Biology Honours Projects Page v
INTRODUCTION
A message from A/Professor Craig Smith, Dr Rob De Matteo, and A/Professor Ann Chidgey – Honours Co-Convenors 2017.
Welcome to the Department of Anatomy and Developmental Biology 2016 Honours Projects Handbook. The Department runs
a stimulating Bachelor of Science and Bachelor of Biomedical Science Honours program accommodating all your academic
requirements. It’s an exciting time to be involved with the Department of Anatomy and Developmental Biology, which is located
in a purpose-built research complex offering state-of-the-art facilities to conduct your Honours degree in style. The Department
is growing from strength to strength, attracting new research groups and is one of Australia’s leading centres for Developmental
Biology.
In 2016, the Department is offering an exciting and extensive choice of Honours projects, ranging from stem cell biology to the
roles of specific genes in organ development and to the progression of adult onset diseases. For strengths within the Department,
visit our Research website for a full list of current research areas (www.med.monash.edu.au/anatomy/honours.html). As you
read through the impressive list of projects throughout this Handbook, we encourage you to contact the relevant research staff
for further information. We would also recommend you talk to current and past students, and demonstrators for extra information.
The overwhelming majority of students who have completed their Honours degree in this Department have had very successful
career outcomes. Most have gained immediate employment, continued on to complete their PhD or enrolled into postgraduate
Medicine or Allied Health courses.
To apply to undertake an Honours year, students should use the Faculty of Science Application Form or the Biomedical Sciences
Application Form available online by mid-September.
Entry Criteria to be eligible for entry into Honours:
Bachelor of Science (Honours) https://www.monash.edu/science/current/honours
Bachelor of Science students wishing to undertake an Honours degree in the School of Biomedical Science (SOBS) have
increased flexibility to complete an Honours degree in the Department of Anatomy and Developmental Biology. Any major in
the School of Biomedical Science will allow you to undertake an Honours degree within the Department of Anatomy and
Developmental Biology.
A distinction grade average (70%) in 24 points of relevant 3rd year units, of which normally 18 points are developmental biology
or biochemistry, human pathology, immunology, microbiology, pharmacology and physiology units. In addition to the
requirements listed above, students must meet the entry requirements for the Science honours program relevant to their course
of enrolment. Enrolment in an honours project is subject to approval of the supervisor and the Honours Convenor.
Closing dates for the Faculty of Science are usually mid November (for both internal and external applicants) – for details please
refer to the website.
Bachelor of Biomedical Science (Honours) http://www.med.monash.edu.au/biomed/honours
An average of 70% or higher in at least 24 points at 3rd year (including 12 points in Biomedical Science core units) for details
please refer to the website.
The closing date for Bachelor of Biomedical Science is usually mid November – for details please refer to the
website.http://www.med.monash.edu.au/biomed/honours/
For more information please contact:
A/Professor Craig Smith
19 Innovation Walk
Level 3, Room 355
Phone: 61 3 9905 0203
Email: [email protected]
Dr Rob De Matteo
19 Innovation Walk
Level 3, Room 347
Phone: 61 3 9902 9108
Email: [email protected]
A/Professor Ann Chidgey
15 Innovation Walk
Level 3, Room 314
Phone: 61 3 9905 0628
Email:[email protected]
2017 Anatomy and Developmental Biology Honours Projects Page vi
DEPARTMENT OF ANATOMY AND DEVELOPMENTAL BIOLOGY
The Department of Anatomy and Developmental Biology is one of six
departments in the School of Biomedical Sciences, which is part of the Faculty
of Biomedical and Psychological Sciences.
The Department is responsible for the delivery of human anatomy teaching in
the medical, physiotherapy, radiography, biomedical science and science
degrees. Teaching is conducted at both the undergraduate and postgraduate
levels. Human anatomy teaching is overseen by the Centre for Human
Anatomy Education, which is located within the Department.
In 2007, the Department introduced the first Bachelor of Science major in
Australia in developmental biology. Developmental biology is the discipline concerned with the development of an adult
organism from a single cell. The BSc major provides foundation studies in embryology, histology and anatomy, and covers such
topics as human development, mechanisms of development, birth defects, stem cells, and regenerative biology and medicine.
Research in the Department is focused on the wider field of developmental biology. Researchers are focused on the molecular
mechanisms responsible for development of specific organs, the consequences for adult health of suboptimal fetal development,
the health consequences of premature birth, and the roles of stem cells in development as well as in regeneration of organs
following disease.
THE MONASH BIOMEDICINE DISCOVERY INSTITUTE
Monash's Biomedicine Discovery Institute (BDI) brings scientists together into cross-disciplinary health and disease-focussed
Discovery Programs to increase the collaborative effort needed to make major discoveries that will provide inroads into national
and global health priority areas. The BDI brings together research teams from multiple disciplines into six health-focussed
Discovery Programs:
Cancer
Cardiovascular Disease
Development & Stem Cells
Infection & Immunity
Metabolic Disease & Obesity
Neuroscience
Within each Discovery Programs are research themes which tackle the big research questions that underlie and ultimately cause
the major diseases and health issues faced by humankind.
The Monash BDI has close ties with many health precincts and industry partners: enabling our discoveries to have impact.
With more than 700 staff, over 100 research teams, close to 300 PhD students and an annual research budget in the vicinity of
$50 million from the NHMRC, ARC, Charities and Industry partners, the Biomedicine Discovery Institute has the scope and
scale to tackle major research questions. The Discovery Programs provide focus for researchers and combined with the scope to
bring Programs together, researchers are able to tackle questions at the interface – the impact of immunity on cancer – how
diabetes leads to cardiovascular problems – what role metabolic interventions can play in killing cancer cells – are just some
examples of current cutting-edge research that scientists within the BDI are undertaking.
The BDI is based at Monash University in the Faculty of Medicine, Nursing and Health Sciences and is part of the three-institute
Discovery Precinct, alongside the Australian Regenerative Medicine Institute (ARMI) and the Monash Institute of Cognitive and
Clinical Neurosciences (MICCN). The precinct is supported by fabulous research infrastructure and talented staff - a combination
that makes innovative discoveries possible.
We have organised projects throughout this Honours project handbook into Discovery Programs and then into Research themes.
For more information about the Monash BDI visit www.monash.edu/discovery-institute.
2017 Anatomy and Developmental Biology Honours Projects Page 7
BDI PROGRAME: CANCER
Epithelial Regeneration Laboratory
www.med.monash.edu.au/anatomy/research/epithelial-regen.html
Project Title Molecular regulation of intestinal stem cells
Main Supervisor A/Prof Helen Abud [email protected] 9902 9113
Other Supervisors Dr Thierry Jarde
Location Clayton Campus, 19 Innovation Walk, Level 2
Outline of project
Background: The lining or epithelium of the intestinal tract is vulnerable to a variety of
pathologies. The intestinal epithelium is a regenerative tissue that is constantly renewed
throughout life via a small population of stem cells. We are interested in how growth and
differentiation of intestinal epithelial cells is regulated and how the balance between cell
proliferation, cell differentiation and cell death is normally established and maintained in
these cells. We have detected several potential regulators of stem cells that may be crucial for
the maintenance of intestinal stem cells and are working to define their mechanism of action.
Project Aims: To analyse the function of key intrinsic and/or extrinsic regulators of intestinal
stem cells.
Techniques: This project will involve analysis of tissue from animals where genes are knocked out in the intestine using
immunohistochemistry and qRT-PCR. Functional studies may also be conducted in organoid culture from mouse and human
tissue. This project combines molecular techniques, immunohistochemistry, FACS, organoid culture and mouse models.
Project Title Role of stem cell activity in the initiation and progression of colorectal cancer
Main Supervisor A/Prof Helen Abud [email protected] 9902 9113
Other Supervisors Dr Thierry Jarde,
Other Supervisors A/Prof Paul McMurrick (Cabrini Hospital)
Location Clayton Campus, 19 Innovation Walk, Level 2
Outline of project
Background: The initial phase of tumour formation in the bowel often involves the
development of polyps before progressing to more invasive, malignant carcinomas. Recent
work has defined intestinal stem cells as the cell of origin of cancer. There is also
considerable evidence suggesting that established bowel tumours are driven by a small
population of cancer stem cells that may also promote metastasis.
Project Aims: We are aiming to analyse the role of molecules identified in intestinal stem
cells at different stages in the progression of colorectal cancer and whether they can predict
response to treatment or relapse.
Techniques: This project will utilize primary tumour tissue from human colorectal
carcinomas at different stages. Studies include the analysis of the expression pattern of stem
cell markers in these samples using dd-PCR, immunohistochemistry and microscopy and
correlation with clinical parameters and outcomes. Studies of stem cell behaviour in primary
organoid cultures may also be studied.
2017 Anatomy and Developmental Biology Honours Projects Page 8
BDI PROGRAME: CANCER
Project Title Functional Screening using intestinal organoids
Main Supervisor A/Prof Helen Abud [email protected] 9902 9113
Other Supervisors A/Prof Ron Firestein (Hudson Institute)
Other Supervisors Dr Thierry Jarde
Location Clayton Campus, 19 Innovation Walk, Level 2
Outline of project
Background: Intestinal organoids derived from human tumours and adjacent normal tissue are a key model for
preclinical studies. Organoids recapitulate the cellular composition and functional features of the original patient tissue
and tumours. Organoids can be expanded and used in screening approaches to test drug response and other functional
assays.
Project Aims: This Project Aims to develop a functional epigenetic CRISPR screen in organoids.
Techniques: This project will involve growth of human colonic organoids. Transfection will be used to introduce
components of the CRISPR Cas 9 system. A gRNA library will then
be screened. Outputs of the assay would include measurement of
growth, apoptosis and morphology of intestinal organoids.
2017 Anatomy and Developmental Biology Honours Projects Page 9
BDI PROGRAME: CANCER
Prostate Cancer Research Group
www.med.monash.edu.au/anatomy/research/prostate-research.html
Project Title Pre-clinical testing of novel combination therapies in mouse models of prostate cancer
Supervisors Dr Mitchell Lawrence [email protected] 9902 9286
Dr Stuart Ellem [email protected] 9902 9514
Prof Gail Risbridger [email protected]
Location Clayton Campus, 19 Innovation Walk, Leve
Outline of project
Background: The prostate requires androgens for normal growth and functioning and the vast
majority of prostate cancer (PC) are dependent on the androgen receptor (AR) for growth and
proliferation. Androgen-deprivation therapy (ADT) remains the mainstay of therapy for advanced PC,
but the disease invariably progress to a stage known as castration-resistant PC (CRPC). The last
decade has seen the development of many new therapeutic agents targeting AR activity directly by
inhibiting its transcriptional activity or indirectly by inhibiting the enzymes responsible for androgens
synthesis. These agents have successfully increased survival in CRPC, but resistance emerges in a
matter of months. It is therefore urgent to develop and validate new therapeutic targets in PC which
are independent of AR activity.
Project Aims: In this project, using genetically modified mouse models (GEMM) of PC, we will test
novel small molecule inhibitors targeting key vulnerabilities of PC cells. In addition, we are also
developing and testing therapeutic antibodies and a new vaccine technology.
Techniques: This project will involve animal work, histology, immunohistochemistry, qPCR and analysis of signalling
pathways by Western blotting.
Project Title New human models for rapid preclinical testing of prostate cancer
Supervisors Dr Mitchell Lawrence [email protected] 9902 9286
Dr Stuart Ellem [email protected] 9902 9514
Prof Gail Risbridger [email protected]
Location 19 Innovation Walk, Monash Clayton Campus
Outline of project
Background: Prostate cancer is the most commonly diagnosed cancer in Victoria.
Unfortunately, our ability to pre-clinically test new therapies is constrained by the paucity of
experimental human models because prostatic tumours are more difficult to grow in the
laboratory than many other types of cancer. However, our laboratory has successfully
developed in vivo and in vitro systems to maintain the viability of rare and valuable patient
samples as patient-derived xenografts, explants or organoids. These samples represent an
invaluable resource for testing novel therapeutics for prostate cancer.
Project Aims: The goal of this project is to use patient-derived xenografts as ex vivo explants
or organoids to test drugs of interest that are in development and identify the most promising
compounds for further in vivo studies.
Techniques: The project will involve a variety of techniques including tissue pathology, tissue
culture and handling, immunohistochemistry, automated image analysis and qPCR.
Cytokeratin and p63
staining of prostate
cancer
Immunohistochemistry of an
explant of prostate cancer
tissue
2017 Anatomy and Developmental Biology Honours Projects Page 10
BDI PROGRAME: CANCER
Project Title Defining epigenome changes in the tumour microenvironment
Supervisors Dr Mitchell Lawrence [email protected] 9902 9286
Dr Stuart Ellem [email protected] 9902 9514
Prof Gail Risbridger [email protected]
Location 19 Innovation Walk, Monash Clayton Campus
Outline of project
Background: The tumour microenvironment has a key role in the progression of
prostate cancer. Our laboratory recently showed that cells within the tumour
microenvironment, known as cancer-associated fibroblasts (CAFs), acquire consistent
changes in DNA methylation. These epigenome marks are highly consistent between
patients and represent possible new biomarkers for improving the accuracy of cancer
diagnosis.
Project Aims: The goal of this project is to use 3D tissue culture models to study how
reciprocal signalling between cancer cells and fibroblasts shapes the pattern of DNA
methylation in each cell type. The results will identify the most important epigenome
marks to validate as new biomarkers for prostate cancer.
Techniques: The project will involve co-cultures of different cell types in custom-
designed 3D scaffolds. The interactions between the cells will be examined using confocal microscopy and image analysis
software. DNA methylation and gene expression changes will be examined using targeted bisulphite sequencing and
quantitative PCR.
Project Title Reconstructing the evolution of therapy-resistance metastatic prostate cancer
Supervisors Dr Mitchell Lawrence [email protected] 9902 9286
Dr Stuart Ellem [email protected] 9902 9514
Prof Gail Risbridger [email protected]
Location 19 Innovation Walk, Monash Clayton Campus
Outline of project
Background: Once prostate cancer becomes metastatic (spreads to other organs) it becomes difficult to treat, and disease
recurrence is common. Our laboratory is investigating how prostate cancer spreads and becomes resistant to therapy by using
next-generation sequencing to detect genetic mutations, epigenetic alterations and changes in gene expression in tumour samples
taken from patients at autopsy.
Project Aims: The goal of this project is to reconstruct how each patient’s cancer evolved before and after treatment, to identify
key mutations and regulatory changes driving therapy resistance and metastasis in prostate cancer.
Techniques: This project will involve in-depth bioinformatics analysis of whole-genome, whole-genome and RNA-sequencing
data, as well as the design and implementation of statistical algorithm for studying tumour evolution.
Whole genome sequencing data from prostate cancer metastases
Cancer-associated fibroblasts
isolated from prostate cancer tissue
2017 Anatomy and Developmental Biology Honours Projects Page 11
BDI PROGRAME: CARDIOVASCULAR DISEASE
Cardiovascular and Renal Developmental
Programming Laboratory
www.med.monash.edu.au/anatomy/research/cardiovascular-renal-dev-programming.html
Project Title Long-Term Impact of Preterm Birth on the Renal Vasculature
Main Supervisor Prof Jane Black [email protected] 9902 9112
Other Supervisors Dr Megan Sutherland [email protected]
Location Clayton Campus, 19 Innovation Walk, Level 3
Outline of project
Background: Born at a time when kidney development is ongoing, preterm neonates are
prematurely exposed to the extrauterine environment with significantly higher oxygen
concentrations than in utero. This in turn leads to oxidative stress, and complications related
to impaired vascular development (such as retinopathy of prematurity). The impact of preterm
birth on vascular development in the kidney, however, is largely unknown. Further, whether
there are long-term pathological changes, such as glomerulosclerosis, is yet to be determined.
The findings from this study are expected to help explain the link between preterm birth and
the development of hypertension and renal dysfunction later in life.
Project Aims: The aim of this study is to investigate the long-term impact of preterm birth
on the glomerular capillaries in a large animal (sheep) model of preterm birth.
Techniques: Stereological techniques will be utilised to assess nephron number and
glomerular capillary growth. Histological analyses of renal pathology will also be undertaken.
Project Title Effect of postnatal steroids on the preterm kidney
Main Supervisor Professor Jane Black [email protected] 9902 9112
Other Supervisors Dr Megan Sutherland [email protected]
Location Clayton Campus, 19 Innovation Walk, Level 3
Outline of project
Background: Preterm infants are born at a time when their kidneys are structurally and
functionally immature. Infants that are born preterm are often treated with steroids in
the neonatal period, which act to accelerate the maturity of their immature organs.
Podocytes are specialised epithelial cells in the glomerulus of the kidney that play a key
role in the glomerular filtration barrier. During normal renal development, podocytes
cease proliferating prior to birth at term. Whether podocyte proliferation continues after
preterm birth and whether postnatal steroids influence podocyte proliferation and
number is unknown and this forms the focus of this project.
Project Aims: The aim of this study is to investigate the effect of very preterm birth
and/or postnatal steroid administration on glomerulogenesis and podocyte growth in a
large animal (sheep) model of preterm birth.
Techniques: Stereological techniques will be utilised to assess glomerular capillary and
podocyte growth.
Glomerulus from a lamb
kidney
Immunohistochemical
labelling of glomerular cell
types
2017 Anatomy and Developmental Biology Honours Projects Page 12
BDI PROGRAME: CARDIOVASCULAR DISEASE
Kidney Development, Programming and Disease
Research Laboratory
www.med.monash.edu.au/anatomy/research/kidney-development-disease-regeneration-group.html
Project Title In chronic kidney disease, does the degree of podocyte depletion influence the success rate of
steroid treatment?
Main Supervisor Dr Luise Cullen-McEwen [email protected] 9902 9106
Other Supervisors Prof David Nikolic-Paterson [email protected]
Prof John Bertram [email protected]
Location Clayton Campus, 19 Innovation Walk, Level 3
Outline of project
Background: Close to 80% of adult patients with podocyte-specific diseases relapse to first line
therapies such as glucocorticoids. As a result, many patients progress to chronic kidney disease
and end-stage kidney disease. The reasons for this variable response to conventional therapies are
largely unknown. We hypothesise that the degree of podocyte depletion in glomeruli is a clinical
indicator of the likely response, or non-response, to steroid therapy.
Project Aims: We will test this hypothesis using our PodCreiDTR transgenic mouse model in
which the human diphtheria toxin (DT) receptor is specifically expressed in podocytes.
Administration of DT to these mice results in dose-dependent podocyte loss. We will compare
the effects of two levels of podocyte depletion (moderate and severe) on disease progression and response to steroid
treatment.
Techniques: Immunofluorescence, confocal microscopy, renal physiology, renal pathology.
Project Title Mild podocyte depletion and its effect on the development of glomerular hypertrophy
Main Supervisor Dr Luise Cullen-McEwen [email protected] 9902 9106
Other Supervisors Prof John Bertram [email protected]
Location Clayton Campus, 19 Innovation Walk, Level 3
Outline of project
Background: Glomeruli of the kidney contain four types of resident cells, one of which is the
podocyte. This cell plays an important role in glomerular filtration and is not able to replicate.
Multiple studies have shown that a reduction in podocyte number is a direct cause of glomerular
scarring during adulthood. This means that the regulation of podocyte number is essential for normal
glomerular function and health. Our laboratory has evidence that in humans without renal disease,
podocyte number is reduced in subjects with hypertension and low nephron number, suggesting that
a number of podocytes may be lost during a person’s lifespan. Glomerular hypertrophy is a
physiological compensation that occurs in multiple types of glomerular injury in order to sustain
renal function. Therefore, it is important to test if mild podocyte depletion can have an effect on
glomerular hypertrophy.
Project Aims: Mild podocyte depletion will be induced using a transgenic mouse model we have generated in our laboratory
(PodocinCre/iDTR). These mice express a mutated diphtheria toxin (DT) receptor only on podocytes, which will allow us
to titrate podocyte depletion based on the doses of DT we inject. Once podocyte depletion has been induced, we will induce
glomerular hypertrophy by the removal of one kidney (50% reduction of renal mass). Given that glomeruli cannot be formed
in adult life, any reductions in renal mass will require the kidney to adjust. We hypothesize that a reduction in podocyte
number after DT injection will limit the capacity of glomeruli to undergo hypertrophy, possibly leading to the development
of renal disease. After 14 weeks (with close renal function monitoring), kidneys will be extracted for the assessment of
glomerular volume, podocyte number, glomerular cell proliferation and pathology.
Techniques: This is an excellent opportunity to learn about the generation of transgenic mouse models. It will allow you to
expand your knowledge of multiple animal procedures, including injections and surgery. You will also learn to estimate
glomerular volume, podocyte number and glomerular function using novel and state of the art techniques.
2017 Anatomy and Developmental Biology Honours Projects Page 13
BDI PROGRAME: CARDIOVASCULAR DISEASE
Project Title Does a maternal low protein diet in mice lead to low podocyte endowment and does this render
mice more susceptible to kidney disease?
Main Supervisor Dr Luise Cullen-McEwen [email protected] 9902 9106
Other Supervisors A/Prof Ian Smyth [email protected]
Prof John Bertram [email protected]
Location Clayton Campus, 19 Innovation Walk, Level 3
Outline of project
Background: Podocytes are critically important components of the glomerular filtration barrier. Podocyte depletion is
associated with the development of the majority of glomerular, and thereby kidney diseases. Three forms of podocyte
depletion are known: (1) loss of podocytes; (2) reduced podocyte density in glomeruli (due to glomerular enlargement); and
(3) altered podocyte structure. We have recently identified a fourth form of podocyte depletion, namely low podocyte
endowment at birth. We found that offspring of rats fed a low protein diet during pregnancy had reduced podocyte
endowment. This is the first report of low podocyte endowment. In this project we will determine whether feeding a low
protein diet to pregnant mice results in low podocyte endowment in offspring, and then assess whether such mice are more
susceptible to kidney disease.
Project Aims: Female mice will be fed a normal protein diet (NPD) or low protein diet (LPD) before mating, during
pregnancy and until weaning. At weaning, kidneys from a subset of NPD and LPD mice will be collected for assessment of
nephron and podocyte number. The remaining mice will receive injections of vehicle or streptozotocin (STZ) to produce
hyperglycaemia. Renal function will be assessed and at 6 weeks of age kidneys will be collected for podocyte counting and
assessment of renal pathology. Podocytes will be visualised with a new technique developed in our laboratory that allows
analysis of whole glomeruli within minutes.
Techniques: Immunofluorescence labelling, tissue clearing, confocal microscopy, renal function, pathology
2017 Anatomy and Developmental Biology Honours Projects Page 14
BDI PROGRAME: DEVELOPMENT AND STEM CELLS
Developmental Diseases Laboratory
www.med.monash.edu.au/biochem/staff/smyth.html
Project Title Understanding normal and abnormal kidney development
Main Supervisor A/Prof Ian Smyth [email protected] 9902 9119
Location Clayton Campus, 19 Innovation Walk, Level 3
Outline of project
Background: Our group studies how the embryo develops with a view to understanding the basis for
congenital diseases and those caused by a compromised fetal environment. In particular we are
interested in understanding the developmental mechanism known as "branching morphogenesis", which
is employed by a large number of organs to establish the tissue architecture required to facilitate
exchange of nutrients, gases or waste in the adult organ. Understanding this process will provide
insights into the developmental origins of congenital diseases and how the "normal" variations observed
in the structure of organs are influenced by their experiences and exposures as an embryo.
Project Aims: Nephron number is highly variable in human populations but the developmental basis for this difference is
poorly understood. This project will utilise our imaging expertise and an array of different models to explore how
perturbations to fetal environment like alcohol intake and maternal diabetes impacts on genetic pathways central to
progenitor cell maintenance and nephron formation. Doing so will help us to understand how kidney disease develops and
what might underlie the enormous variation in nephron number which is an important predictor of kidney failure and
hypertension. Ref - Short KM*, et al. (2014) Global quantification of tissue dynamics in the developing mouse kidney.
Developmental Cell. 29(2):188-202.
Techniques: This project will utilise techniques applicable to both embryology and molecular biology including histology,
microscopy, dissection, immunofluorescence in vitro assays for assessing gene expression and epigenetic modification.
Project Title Dissecting the molecular basis of congenital kidney diseases
Main Supervisor A/Prof Ian Smyth [email protected] 9902 9119
Location Clayton Campus,19 Innovation Walk, Level 3
Outline of project
Background: Our group studies how the embryo develops with a view to understanding the basis for
congenital diseases and those caused by a compromised fetal environment. In particular we are
interested in understanding the developmental mechanism known as "branching morphogenesis", which
is employed by a large number of organs to establish the tissue architecture required to facilitate exchange
of nutrients, gases or waste in the adult organ. Understanding this process will provide insights into the
developmental origins of congenital diseases and how the "normal" variations observed in the structure
of organs are influenced by their experiences and exposures as an embryo.
Project Aims: Abnormal kidney development is one of the most common birth defects. We are pursuing
a number of projects aimed at understanding their mechanistic and biochemical basis with a particular focus on renal cyst
development and vesicoureteral reflux (VUR). One project in this area will focus on examining cyst development in the
kidney and explore the interactions between the primary cilia-associated proteins Inpp5e and Aurka. Our group is also
involved in an Australia-wide program which aims to identify novel genes in patients with kidney disease. These individuals
will have their genomes sequenced and we will then use CRISPR/Cas9 genome engineering approaches to model disease
causing mutations in mice. Using these models, honours students will have a unique opportunity to establish how novel
disease genes function in the kidney, how their protein products regulate cell biology and how their mutation leads to
congenital renal malformations. Ref – Plotnikova et al. (2015) INPP5E interacts with AURKA, linking phosphoinositide
signalling to primary cilium stability. Journal of Cell Science. 128(2):364-72.
Techniques: This project will utilise techniques applicable to both embryology and molecular biology including histology,
microscopy, dissection, immunofluorescence in vitro assays for assessing gene expression and epigenetic modification.
2017 Anatomy and Developmental Biology Honours Projects Page 15
BDI PROGRAME: DEVELOPMENT AND STEM CELLS
Male Infertility and Germ Cell Biology
Laboratory
www.med.monash.edu.au/anatomy/research/male-infertility-germ-cell-biology.html
Project Title Microtubule severing proteins and their importance in male fertility and behaviour
Main Supervisor Prof. Moira O’Bryan [email protected] 9902 9283
Other Supervisors A/Prof. Siew Chai [email protected] 9905 2515
Location Clayton Campus, 19 Innovation Walk, Level 3, and
The Department of Physiology
Outline of project
Background: Microtubules are a key component in all cells. Appropriate microtubule
regulation, including by severing proteins, is however, of critical importance in male germ cells
and neurons. The focus of this project is a group of microtubule severing proteins known as the
katanins, for which data from mutant mouse models, generated in the supervisors’ laboratories,
is suggesting a critical role in multiple aspects of sperm development and behaviour.
Project Aims: To elucidate the full suite of behavioural abnormalities in katanin-mutant mice
and to partially define the biochemistry of katanin subunit function using germ cells as a model
system. This project could be adapted to suit either an honours student of a PhD student.
Techniques: This project will utilise techniques including: behavioural testing, immunochemical methods, cell culture,
animal handling, histology and biochemistry. This project would suited to a student with a good grounding in biochemistry
and cell biology.
Project Title The function of a novel sperm tail protein in male fertility
Main Supervisor Prof. Moira O’Bryan [email protected] 9902 9283
Other Supervisors Dr Hidenobu Okuda [email protected] 9902 9111
Location Clayton Campus, 19 Innovation Walk, Level 3
Outline of project
Background: Spermiogenesis is the process wherein haploid male germ cells are transformed
from a traditional looking round cell into the highly polarized sperm, with the capacity for
motility and fertility. Key aspects of this transformation include the shaping of the sperm head
and the development of the sperm tail. Recently the O’Bryan lab has identified a largely
uncharacterized protein which they hypothesis has a role in both of these developmental
processes. Towards testing this hypothesis, we have demonstrated the localization of the
protein to the manchette, which is involved in sperm head shaping, and the developing sperm
tail. Further, we have demonstrated that this protein is quantitatively reduced in a significant
number of infertile human men, thus raising the prospects of it being used as a biomarker prior
to infertility treatment.
Project Aims: To identify binding proteins involved in the function of this protein using primary cilia as a model system and
to validate their role in germ cell development using a knockout mouse model.
Techniques: This project will utilise techniques including: cell culture, mass spectrometry and protein chemistry, and
immunochemistry. This project is ideally suited to an honours student with a background in biochemistry and cell biology.
2017 Anatomy and Developmental Biology Honours Projects Page 16
BDI PROGRAME: DEVELOPMENT AND STEM CELLS
Neuronal Development and Plasticity Laboratory
www.pococklab.org
Project Title How to control aggregation of toxic proteins? A conserved microRNA holds the key.
Main Supervisor A/Prof Roger Pocock [email protected] 9905 0654
Location Clayton Campus, 15 Innovation Walk, Level 3
Outline of project
Background: Aggregation of toxic proteins is a hallmark of multiple pathological states including Alzheimer’s disease,
Huntington’s disease and muscular atrophy. The involvement of microRNAs in the control of protein aggregation is poorly
understood. The Pocock laboratory has recently identified that muscle-specific mir-1 is a crucial regulator of polyglutamine-
induced protein aggregation in Caenorhabditis elegans.
Project Aims: In this project, we will investigate the molecular mechanism through which mir-1 controls protein aggregation.
The findings generated in this project will have important implications in protein aggregation disorders and will potential
identify novel therapeutic approaches.
Techniques: This project will utilise techniques in genetics, molecular biology, biochemistry and microscopy.
Figure: mir-1 mutant exhibiting excess protein
aggregation of a Huntington’s Disease Model protein
.
0
20
40
60
80
100
Nu
mb
er
of a
gg
reg
ate
s
Muscle::Q0 Muscle::Q40
WT mir-1
nullWT mir-1
null
****
mir-1 null; muscle Q40
2017 Anatomy and Developmental Biology Honours Projects Page 17
BDI PROGRAME: DEVELOPMENT AND STEM CELLS
Oocyte and Embryo Development Laboratory
www.med.monash.edu.au/anatomy/research/oocyte-and-embryo-development.html
Project Title Study of mitochondrial biogenesis and dynamics during oogenesis
Main Supervisor Prof John Carroll [email protected] 99024381
Other Supervisors Dr Deepak Adhikari [email protected] 99020120
Location Clayton Campus, 19 Innovation Walk, Level 3
Outline of project
Background: Mitochondria are double-membraned cellular organelles containing their own mtDNA and they play crucial
roles in energy production, calcium metabolism, and apoptosis. In contrast to nuclear DNA, mtDNA is transmitted
exclusively through maternal inheritance, i.e. through eggs. During oocyte development, both the number of mitochondria
and mtDNA copy number increase rapidly. At the same time mitochondria are highly dynamic and undergo fission, fusion,
transport and degradation during oocyte maturation. Recent findings suggest that mitochondrial dynamics is closely related
to the cellular metabolism. It is not clearly understood how these processes during oocyte development are interrelated and
are affected by maternal aging and obesity, both of these conditions are known to affect the quality of eggs generated.
Project Aims: In this project, we will investigate the aspects of mitochondrial dynamics and mtDNA replication during
oogenesis and their effects in the quality of eggs. These findings will have broad implications for understanding the roles of
mitochondria in the development of eggs and for the future development of assisted reproductive technologies.
Techniques: This project will utilise genetically modified mouse models, which will be studied by techniques like ovary
histology, in vitro oocyte maturation, live cell imaging, immunofluorescence, quantitative PCR.
Different morphology of mitochondria
(green) in meiotically arrested (a) and
maturing (b) mouse oocytes.
2017 Anatomy and Developmental Biology Honours Projects Page 18
BDI PROGRAME: DEVELOPMENT AND STEM CELLS
Ovarian Biology Laboratory
www.med.monash.edu.au/anatomy/research/ovarian-biology.html
Project Title Uncovering the molecular mechanisms that determine the length of the female fertile lifespan
Main Supervisor Dr Karla Hutt [email protected] 99050725
Other Supervisors Dr Jason Liew [email protected]
Location Clayton Campus, 19 Innovation Walk, Level 3
Outline of project
Background: More than two thirds of the germ cells produced during female
embryonic development undergo apoptosis shortly after they are made. This
leaves a reduced number of oocytes within the ovary at birth, and, because new
germ cells cannot be made after this point, it limits female fertility and
reproductive lifespan. Despite the critical role of apoptosis in regulating the
number of available oocytes, and hence in determining the length of a women’s
fertile lifespan and the timing of menopause, it is not understood how or why
these germ cell die en masse.
Project Aims: This project will use a knockout mouse model to investigate the
role of a pro-apoptotic protein, BID, in regulating germ cell/oocyte death.
Additionally, the relationship between oocyte number and the female
reproductive lifespan will be determined.
Techniques: Techniques you will learn/use include qRT-PCR, immunofluorescence, confocal microscopy, histology,
stereology, organ culture and Western Blotting.
Project Title Characterising ovarian damage caused by anti-cancer treatment
Main Supervisor Dr Karla Hutt [email protected] 99050725
Other Supervisors Dr Jess Stringer [email protected]
Location Clayton Campus, 19 Innovation Walk, Level 3
Outline of project
Background: Irreversible damage to the ovary is a devastating
side effect of many anti-cancer treatments, often leaving cancer
survivors unable to have their own children and facing
premature menopause. In particular, these treatments can
damage the DNA of eggs and induce their death, leading to
premature ovarian failure and infertility. Currently, no options
exist to protect the ovary from damage and preserve fertility of
young women being treated for cancer. This limitation is partly
because the exact nature of the ovarian damage caused by
anticancer treatments is not well characterised.
Project Aims: Using irradiation and 2 different mouse models, this project will identify the ovarian cell types that sustain
damage following treatment, and the damage response pathways activated within the ovary will be characterized in detail.
Techniques: Techniques you will learn/use include qRT-PCR, histology, immunofluorescence, confocal microscopy,
histology, stereology and Western blotting.
Ovary from new born mouse
containing numerous immature
oocytes (green).
2017 Anatomy and Developmental Biology Honours Projects Page 19
BDI PROGRAME: DEVELOPMENT AND STEM CELLS
Palaeodiet Research Lab
www.med.monash.edu.au/anatomy/research/palaeodiet.html
Project Title Dental wear development in children
Main Supervisor Dr Luca Fiorenza [email protected] 0399059809
Location Clayton Campus, 10 Chancellors Walk, Level 1
Outline of project
Background: Dental wear is a natural and inevitable process consisting in the gradual loss
of the enamel layer. Different mechanisms, such as erosion, attrition and abrasion are
involved in the creation of tooth wear. However, is still not clearly understood how wear
patterns form and develop.
Project Aims: For this project we will use digital models of dental casts taken from
Aboriginal children of the Yuendumu Reserve (Northern Territory), who were annually
observed between 1951 and 1971. Thus we will have the possibility to give a clear insight
on wear development variation between individuals and within the same person over time.
Moreover, because the Aboriginal people from Yuendumu were at an early stage of
transition from a nomadic and hunter-gatherer way of life to a more settled existence, we
can further examine the relationship between craniofacial structures and occlusal loading in
normal and altered (e.g. misalignment of teeth) masticatory systems.
Techniques: The project will use a well-established method called Occlusal Fingerprint
Analysis (OFA), which describes the major jaw movements in a 3D space. The methods
may have potential applications in medicine and orthodontics.
Project Title Functional morphology of primate teeth
Main Supervisor Dr Luca Fiorenza [email protected] 0399059809
Other Supervisors Dr Alistair Evans [email protected]
Location Clayton Campus, 10 Chancellors Walk, Level 1
Outline of project
Background: Primates feed on different food sources and this difference can be
reflected in the size and shape of their teeth. However, while the shape of unworn teeth
can suggest what a tooth is capable of processing, tooth wear can tell us how a tooth
was actually used.
Project Aims: The focus of this study will be on the relationship between tooth
morphology, dental wear and mastication in primates with different ecological
adaptations. This project will be based on a novel approach that uses advanced 3D
digital modeling of primate teeth and it will help to better understand the relationship
between jaw movements, wear and food physical properties. The results will be later
on used as model for understanding ecological and evolutionary adaptations of our
closest African ancestors.
Techniques: The project will be based on advanced digital techniques that use 3D medical and engineering imaging software
that could be potentially used in orthodontics and biology.
2017 Anatomy and Developmental Biology Honours Projects Page 20
BDI PROGRAME: DEVELOPMENT AND STEM CELLS
RNA Processing and Development
Laboratory
www.med.monash.edu.au/anatomy/research/rna-processing-and-development-laboratory.html
Project Title RNA processing pathways in adult stem cells
Main Supervisor Dr Minni Anko [email protected] 9905 0622
Location Clayton Campus, 15 Innovation Walk, Level 3
Outline of project
Background: Pluripotent stem cells give rise to all cells of an organism
during development but also adult organisms harbour tissue specific stem
cells that can differentiate into limited number of cell types. In addition to
developmental defects, dysregulation of stem cell activity plays a central
role in many diseases, such as cancer. We have identified RNA binding
proteins that play a critical role in multiple adult stem cell niches. It is not
known if these proteins regulate same RNA processing pathways in all stem
cells or if stem cells of different origin are regulated through distinct target
RNAs.
Project Aims: We have generated mouse and in vitro models to investigate
the expression and function of SR proteins in adult stem cells. This project
compares RNA-mediated control of stem cells in the gut, testis and bone
marrow. The aim is to isolate specific common core stem cell pathways as
well as regulatory mechanisms employed by only distinct stem cell types.
Techniques: This project provides an opportunity to work with mouse and tissue culture models as well as to learn a wide
range of molecular biology techniques, flow cytometry (exemplified in the figure, left) and imaging (figure, right).
Project Title RNA regulation during zebrafish development
Main Supervisor Dr Minni Anko [email protected] 9905 0622
Other Supervisors Dr Jan Kaslin [email protected] 9902 9613
Location Clayton Campus, 15 Innovation Walk, Level 3
Outline of project
Background: Maintenance of distinct stem cell pools is crucial during embryonic development and failure to regulate stem
cell activity leads to developmental defects. Dynamically regulated gene expression programs determine cell fate but in
particular the role of post-transcriptional regulation is not well understood. Increase in understanding how gene regulation
at the level of RNA functions during development will take us closer to our long-term goal to develop better treatments for
disease conditions where developmental or growth control has gone awry.
Project Aims: This project investigates RNA binding protein activities during development by using zebrafish as a model.
Zebrafish provides many advantages to study early development, including transparency of embryos and large number of
progeny. By using Cripr/Cas genome editing technology we have generated knockout zebrafish lines where the expression
of distinct RNA binding proteins is ablated. In conjunction with transient overexpression and knockdown approaches, the
novel loss of function zebrafish lines will be characterised and used to investigate the role of post-transcriptional gene
regulation during zebrafish development, in the function of stem cells and differentiation of specific cell types.
Techniques: This project provides an opportunity to study
zebrafish development using techniques such as embryo
manipulation, imaging, in situ hybridization and other
molecular biology techniques.
2017 Anatomy and Developmental Biology Honours Projects Page 21
BDI PROGRAME: DEVELOPMENT AND STEM CELLS
Project Title No nonsense – gene expression control in stem cells
Main Supervisor Dr Minni Anko [email protected] 9905 0622
Location Clayton Campus, 15 Innovation Walk, Level 3
Outline of project
Background: RNA processing mediated by RNA binding proteins entails
fundamental processes for the expression of all genes because each newly
transcribed RNA needs to undergo multiple processing steps to become
functional and stable. Accurate RNA processing is critical during
development and throughout life because incorrect RNAs are deleterious
for cells. Nonsense mediated decay (NMD) removes deleterious, aberrant
transcripts arising from errors in transcription or mutations. NMD
pathway is not only dedicated to the removal of aberrant mRNAs but
normal transcripts can be degraded by NMD to downregulate their
expression. The dual role of NMD highlights its central role in gene
regulation. We have identified a novel mediator linking nuclear RNA
processing steps to NMD in the cytoplasm to safeguard faithful gene
expression in stem cells and during differentiation.
Project Aims: The dynamic interaction of RNA binding proteins with
RNA is critical for RNA processing. The key unanswered question in the field is how different RNA regulators faithfully
distinguish their target RNAs from non-targets in different cell types. This project helps to unravel the mystery of NMD
target selection by studying a novel mechanism of mRNA recognition. The aim is to define how RNA processing is coupled
to NMD to regulate the expression of specific mRNAs, and how this contributes to the regulation of gene expression in stem
cells.
Techniques: This project provides an opportunity to learn a wide range of molecular biology techniques as well as tissue
culture, flow cytometry and imaging. Depending on the interests of the student, it is possible to incorporate bioinformatics
component into the project.
Combination of cell biology, RNA biology
and bioinformatics to reveal how stem
cells are regulated.
2017 Anatomy and Developmental Biology Honours Projects Page 22
BDI PROGRAME: DEVELOPMENT AND STEM CELLS
Polo Group:
Reprogramming and
Epigenetics
Project Title Understanding and exploding the reprogramming Process
Main Supervisor A/Prof Jose Polo [email protected] 990 50005
Other Supervisors Dr Anja Knaupp [email protected]
Other Supervisors Dr Christian Nefzger [email protected]
Location Clayton Campus, 15 Innovation Walk, Level 3
Outline of project
The laboratory is interested in the transcriptional and epigenetic mechanisms that govern cell identity, in particular
pluripotency and the reprogramming of somatic cells into induced pluripotent stem (iPS) cells.
Being able to reprogram any specific mature cellular program into a pluripotent state and from there back into any
other particular cellular program or to direct reprogram a any cell type into any other provides a unique tool to dissect
the molecular and cellular events that permit the conversion of one cell type to another. Moreover, iPS cells and the
reprogramming technology are of great interest in pharmaceutical and clinical settings, since the technology can be
used\ to generate animal and cellular models for the study of various diseases as well in the future to provide specific
patient tailor made cells for their use in cellular replacement therapies. By using a broad array of approaches through
the use of mouse models and a combination of different molecular, biochemical, cellular techniques and genome wide
approaches, our lab will aim to dissect the nature and dynamics of such events.
Projects available for honours students:
1) The kinetics and universality of the epigenetic and genomic
changes occurring during reprogramming.
2) The composition and assembly kinetics of transcriptional
regulation complexes at pluripotency genes.
3) Using computational and empirical models to generate new
direct cell conversion for Kidney disease, Dementia and Blood
disorders.
You will spend a year doing the most advance and exciting
science, learning about stem cells hands-on and a wide range
of practical lab skills. These exciting, intense projects requires
a highly motivated, dedicated, adaptable student. We are fast-
paced & fun, but we work hard - please only apply if you
thrive in this sort of environment.
Publications:
Firas et al., Nature Genetics 2016
David and Polo, Stem Cell Research 2014
Polo et al , Cell 2012
Polo et al, Nature Biotech 2010
2017 Anatomy and Developmental Biology Honours Projects Page 23
BDI PROGRAME: INFECTION AND IMMUNITY
Stem Cells and Immune
Regeneration Laboratory
http://www.med.monash.edu.au/anatomy/research/immune-regeneration.html and
http://www.med.monash.edu.au/biochem/labs/lagruta-lab.html
Project Title Evaluating the functional potential of regenerated CD8 T cells in aged mice
Main Supervisor A/Prof Ann Chidgey [email protected] 9905-0628
Other Supervisor
Other Supervisor
Prof Nicole La Gruta
Dr Kylie Quinn
9902-9182
9905-5550
Location Clayton Campus, 15 Innovation Walk, Level 3
Outline of project
Background:
Our immune system naturally diminishes in function as we age and this can lead to an increased susceptibility to infections
and poor immune recovery following cytoablative treatments associated with cancer therapy. One of the main causes is the
natural degeneration of the thymus, the primary site for T cell production, but may also involve influences from an ageing
milieu. In addition to the reduced size of the T cell pool, the aged T cell pool exhibits marked phenotypic and functional
changes associated with diminished capacity. We have developed an endocrine-based approach for thymus and T cell
regeneration in middle-aged mice, however, we have not fully investigated the longevity and functional potential of these
newly generated T cells.
Project Aims: In this project, we will determine whether
regenerated CD8+ T cells in aged mice resemble CD8+ T cells
from young animals, with regard to phenotype, function and
longevity, thereby establishing whether this approach holds the
potential to rescue cellular immune responses in the elderly.
We will assess a number of phenotypic and functional aspects of
newly regenerated CD8+ T cells, including: expression of markers
such as CD44, CD5 and others that are typically elevated in aged
CD8+ T cells, the transcriptional profile of newly generated CD8+
T cells as compared to conventional young or aged CD8+ T cells,
the ability of these cells to respond to stimulation in vitro with
proliferation and production of cytokines or in vivo with
recruitment into infection- and vaccine-induced immune
responses to stimulation, and the ability of these cells to survive in
vivo.
Techniques: Flow cytometry, RNA-Seq and data analysis, in vitro
cell culture, animal handling.
Fig. 1: Schematic of the proposed project-
defining the potential and function of
regenerated CD8+ T cells
2017 Anatomy and Developmental Biology Honours Projects Page 24
BDI PROGRAME: NEUROSCIENCE
Nervous System Development and Repair
Laboratory
www.neumannlab.com
Project Title Morphogenesis of brain size and shape
Main Supervisor Dr Brent Neumann [email protected] 03 9905 0670
Location Clayton Campus, 15 Innovation Walk, Level 3
Outline of project
Background: Incorrectly regulating brain size or shape during development leads to reduced brain function including motor,
sensory and cognitive impairment. Nevertheless, the developmental processes controlling brain size and shape are poorly
understood. This is partly due to the complexity of brain structure, but also due to a lack of appropriate tools to study brain
development.
Project Aims: This project aims to develop a
landmark-based system for characterizing brain size
and shape in the nematode C. elegans, and to quantify
changes over developmental time and in response to
altered environmental conditions.
Techniques: This project will utilise techniques
applicable to genetics and molecular biology, and will
have a large focus on fluorescence microscopy.
Project Title Cellular and molecular mechanisms of axonal regeneration
Main Supervisor Dr Brent Neumann [email protected] 03 9905 0670
Location Clayton Campus, 15 Innovation Walk, Level 3
Outline of project
Background: Injuries to the nervous system can cause lifelong disabilities due to ineffective repair of the damaged nerve
fibres and thus, understanding the basic molecular mechanisms regulating axonal regeneration is essential for the
development of effective therapies.
Project Aims: This research project will use the nematode C. elegans as a model system to study the molecular mechanisms
behind axonal regeneration, and will utilise a UV laser to cut individual axons in living animals, allowing their response to
injury to be monitored over time. The role of specific molecules in modulating the regenerative response will be analysed.
Techniques: This project will utilise techniques in
genetics, molecular biology, and fluorescence
microscopy.
2017 Anatomy and Developmental Biology Honours Projects Page 25
CENTRE FOR HUMAN ANATOMY EDUCATION
3D Printing Laboratory (Dr Justin Adams, Prof Paul McMenamin, Michelle Quayle)
www.med.monash.edu.au/anatomy/info/centre.html
Project Title Creating a human hand for surgical simulation
Main Supervisor Prof Paul McMenamin [email protected] 99056215
Other Supervisors Dr Justin Adams
Other Supervisors Ms Michelle Quayle
Location 3D Printing Lab, CHAE, 20 Chancellors walk
Outline of project
Background: Surgical training, like the training of airline pilots, is increasingly moving into the realm of simulation.
Training hand surgeons is hampered by access to real human cadaver hands which can be used to teach skills, anatomy and
surgical methods. Many countries do not have access to cadavers or dedicated facilities for dealing with human tissue.
Project Aims: The aim of this project will be to create a 3D printed multicolour, multimaterial anatomically accurate hand
for surgical training.
Techniques: It will require detailed dissections of human hands, imaging and scanning (CT /laser/MRI) and computer aided
design skills to create a series of 3D files of bones, muscles, nerves, vessels, tendons, skin etc from the captured data that
can be printed in different materials in one 3D printer.
2017 Anatomy and Developmental Biology Honours Projects Page 26
CENTRE FOR HUMAN ANATOMY EDUCATION
Fogg Laboratory
www.med.monash.edu.au/anatomy/info/quentin-fogg-centre-bio.html
Project Title 3D Quantitative morphometry of the anterior talofibular ligament: a surgical perspective
Main Supervisor Dr Quentin Fogg [email protected] 9905 0816
Location Clayton Campus, 10 Chancellors Walk, Level 1
Outline of project
Background: Technique and rationale of surgical repair of the lateral and anterior ankle
ligaments is highly debated. Underlying this in an unclear understanding of the detailed
anatomy in a true three dimensional space. Of particular note is the arrangement of the
anterior talofibular ligament. Failure to repair defects of this ligament sufficiently leads to
an accelerated degenerative decline of the mid-tarsal joints.
Project Aims: This study firstly aims to quantify the arrangement of the human talofibular
ligament in 3D space. The angulation in different foot position, and the specific attachment
points and fibre arrangement will be measured. Using the models generated, ligament
failure and the effects of repair will be simulated to determine the most effective arrangement for stability and range of
motion.
Techniques: This study will use dissection of real foot specimens together with medical imaging (radiology) and 3D
reconstructive techniques. The 3D models created will then be analysed in a virtual environment in which different
arrangements and loading patterns can be simulated. Experience in these techniques is NOT required. The project will be
based in the Centre for Human Anatomy Education, where excellent resources and facilities will allow ample opportunity to
learn a variety of techniques. This project is ideal for someone interested in a clinical career, or with an interest in human
form and function, and a research/academic career in anatomy.
Project Title The ulnar ligament complex of the wrist: a modern anatomical puzzle
Main Supervisor Dr Quentin Fogg [email protected] 9905 0816
Other Supervisors John Crock (Dandenong Hospital)
Location Clayton Campus, 10 Chancellors Walk, Level 1
Outline of project
Background: The ulnar margin of the human wrist is complicated and the focus of
much clinical and research attention. Inherent to the unpredictable clinical outcomes
of many restorative and reconstructive surgical procedures in this area is the lack of
consensus regarding the anatomy. The triangular fibrocartilage complex (TFCC) is a
collection of structures that are poorly understood. Key to the stability of the TFCC is
its ulnar ligamentous column, often termed the ulnar ligament complex. The ULC is
described in many different ways, but never consistently. With a better understanding
of its anatomy, surgical techniques can be selected, or modified, to improve patient
outcomes.
Project Aims: The aim of this project is to quantify the arrangement of the ulnar ligament complex in human wrists. The
project will describe the fibre orientation and connectivity of ligamentous fascicles in this complex, and model them in a 3D
virtual environment. The final aim is to determine what parts of the ULC are essential to TFCC stability.
Techniques: This study will use dissection of real hand specimens together (an example is shown below) with medical
imaging (radiology) and 3D reconstructive techniques. The 3D models created will then be analysed in a virtual environment
in which different arrangements and loading patterns can be simulated. Experience in these techniques is NOT required. The
project will be based in the Centre for Human Anatomy Education, where excellent resources and facilities will allow ample
opportunity to learn a variety of techniques. This project is ideal for someone interested in a clinical career, or with an
interest in human form and function, and a research/academic career in anatomy.
2017 Anatomy and Developmental Biology Honours Projects Page 27
EDUCATION FOCUSED
Centre for Human Anatomy
Education: Lazarus Lab
http://www.med.monash.edu.au/anatomy/info/michelle-lazarus-centre-bio.html
Project Title The Impact of Online Discussion on Student Learning and Development
Main Supervisor Michelle Lazarus [email protected] 99050732 Location Clayton Campus, 10 Chancellors Walk, Level 1
Outline of project
Background:
There are often calls to improve relevant on-line/digital learning environments, to move away from
lectures in favour or student-led discussions, and enhancing critical thinking in class. Here we will
be analysing a commercially available “flipped-classroom” digital learning (Verso©) environment
to identify the role it plays in student learning and professional development.
Project aim/s:
Aim 1: Identify the impact of Verso on student engagement outside the classroom
Aim 2: Evaluate the impact of timing and phrasing for discussion prompts.
Aim 3: Make recommendations about, timing, discussion prompt structure, and content for others wanting to use
digital media for classroom learning.
Techniques to be utilised:
This project will utilize both quantitative and qualitative techniques. Both of these
approaches are essential for anyone interested in clinical medicine or a career
focused around education. Skills will be gained in the scientific method, by
designing surveys and focus group discussions to test the role of the Verso on
student learning and professional development.
Project Title The Impact of Online Discussion on Student Learning and Development
Main Supervisor Michelle Lazarus [email protected] 99050732 Location Clayton Campus, 10 Chancellors Walk, Level 1
Outline of project
Background:
Communication between physicians about patient care impacts patient outcomes. however, this skillset is oft
reported as sub-par in the hospital. We have developed a method for introducing an essential clinical
communication method for patient handovers (when a doctor is leaving their shift and must communicate the
patients’ status and needs to the oncoming caregiver) known as the anatomic SBAR, and have previously assessed
this in another institution.
Project aim/s:
Aim 1: Identify the impact of the Anatomic SBAR on Monash Students
Aim 2: Evaluate the impact of the Anatomic SBAR on students’ performance in standardized patient exams
Aim 3: Evaluate the impact of the Anatomic SBAR on student outcome (exam performance).
Techniques to be utilised:
This project will utilize both quantitative and qualitative techniques. Both of these approaches are essential for
anyone interested in clinical medicine or a career focused around education. Skills will be gained in the scientific
method, by designing surveys and focus group discussions to test the role of the communication on student learning
and professional development.
2017 Anatomy and Developmental Biology Honours Projects Page 28
EDUCATION FOCUSED
Project Title The Impact of Twitter on Developing Communities of Practice and Engagement
Main Supervisor Michelle Lazarus [email protected] 99050732 Location Clayton Campus, 10 Chancellors Walk, Level 1
Outline of project
Background:
The use of social media, and the impact of its role in education is hotly debated. While
there are often calls for educators to engage in using social media, there are few
recommendations on the ways to engage this platform. In addition, the relevant social
media platforms (from the students’ perspective) is regularly changing. The aims of this
project are to evaluate a novel use of Twitter on the followers; specifically we will be identifying the impact of the
@AskAnatomist site on its twitter followers and identifying the role that similar uses of social media may have
within the broader community.
Project aim/s:
Aim 1: Identify the role the @AskAnatomist has on the community (both general and anatomical) in terms of
impact, potential collaborations, and increasing others’ exposure
Aim 2: Identify the themes associated with the @AskAnatomist hashtag (#AnatQ) to determine whether there are:
areas of controversy, areas for further research, and/or areas most likely to illicit discussion.
Aim 3: Make recommendations for others wanting to engage an
audience in topics related to STEM education on twitter, based
on findings from Aim 1 and 2.
Techniques to be utilised:
This project will utilize both quantitative and qualitative
techniques. Both of these approaches are essential for anyone
interested in clinical medicine or a career focused around
education. Skills will be gained in the scientific method, by
designing surveys and experiments to test the role of the
@AskAnatomist twitter feed in the community. Additionally,
analysis of tweets to identify themes associated with the weekly
tweetchat will be undertaken.
2017 Anatomy and Developmental Biology Honours Projects Page 29
THE HUDSON INSTITUTE
Sex Determination and Gonadal Development
Laboratory
www.hudson.org.au/sex-determination-and-gonadal-development/
www.hudson.org.au/profile-prof-vincent-harley/
Project Title Identifying novel sex determination genes responsible for DSD
Research Theme Women’s, Children’s and Reproductive Medicine
Main Supervisor Prof Vincent Harley [email protected] 8572 2527
Location Hudson Institute of Medical Research
Outline of project
Background: Disorders of sex development (DSDs), formerly intersex are congenital conditions where gonadal or
anatomical sex is atypical. DSDs encompass a wide range of abnormalities, including hypospadias (abnormal urinary
opening in males), gonadal dysgenesis (underdeveloped or imperfectly formed gonads), and ambiguous genitalia and sex
reversal (ie XX males and XY females).
Project Aims: Our aim is to identify genes causing DSDs, and the molecular mechanisms underlying testis and ovary
formation in the mammalian embryo.
Techniques: This proposal will provide new insights into the molecular control of testis development, and thus offer the
potential to improve diagnosis and clinical management of DSD. Approaches include human genetics, as well as molecular,
cell and developmental biology.
Reading
Ono, M. and Harley, V. (2013) Disorders of sex development: new genes, new concepts. Nature Reviews Endocrinology
9(2): 79-91. NHMRC Program on DSD: http://dsdgenetics.org/
Regulatory networks during gonadal development. Genes in upper case cause DSD when mutated
2017 Anatomy and Developmental Biology Honours Projects Page 30
THE HUDSON INSTITUTE
Project Title FGF signalling and sex reversal
Research Theme Genetic Diseases
Main Supervisor Prof Vincent Harley [email protected] 8572 2527
Other Supervisors Dr Daniel Bird [email protected] 8572 2505
Location Hudson Institute of Medical Research
Outline of project
Background: We have identified the first FGFR2 mutations in XY female sex reversed DSD patients. One case, a
heterozygous FGFR2c-C342S mutation in a patient with both 46,XY gonadal dysgenesis and Crouzon syndrome is unusual
since gonadal defects have not yet been reported in Crouzon patients.
Project Aims: We will use our ‘knockin’ Fgfr2cC342Y and ‘knockout’ Fgfr2c-/- mouse models to understand the role of
FGFR2 in testis determination and disease and to identify FGFR2-regulated genes and signalling pathways which might be
defective in DSD patients.
Techniques: Analyses of male and female markers will be carried
out, as well as markers of FGF signalling. Training includes basic cell
and molecular biology as well as: embryonic microdissection, whole
mount/section in situ hybridisation and immunofluorescence.
A. Structure of the FGFR2 protein and position of two human
mutations in XY females in red.
B. Immunofluorescence of embryonic gonads from FGFR2c-
C342Y knock-in mouse showing nearly complete sex-reversal
(middle panel).
Project Title Characterisation of novel gonadal targets of Sox9
Research Theme Women’s, Children’s and Reproductive Medicine
Main Supervisor Prof Vincent Harley [email protected] 8572 2527
Other Supervisors Dr Monica Caggiano [email protected] 8572 2905
Location Hudson Institute of Medical Research
Outline of project
Background: For the majority of DSD cases the underlying genetic
aetiology is unknown. In males the Sry gene (testis determining factor)
located on the Y chromosome upregulates the expression of Sox9, a
critical ‘hub’ gene involved in male sexual development. However little
is known about its downstream targets. By extensive data mining of
gonadal microarrays, RNAseq, and SOX9 ChIPseq we have identified
genes directly regulated by SOX9. These candidate genes are up
regulated in XY mouse testis compared to XX ovaries during
development. See for example the expression of Bex2), and down
regulated in sex reversed XY ovaries ablated for Sox9.
Project Aims: We will examine the expression profile of these genes
during the critical sex determining period in a wildtype setting.
Techniques: We will perform detailed expression profiling in XX and
XY embryonic gonad of wild type mice during the critical sex determination period E11.5-E13.5, postnatally and at adult
stages. We will also perform SOX9 ChIPseq on gonads and promoter/enhancer analyses.
2017 Anatomy and Developmental Biology Honours Projects Page 31
THE HUDSON INSTITUTE
Brain and Gender Laboratory
www.hudson.org.au/brain-and-gender/ http://hudson.org.au/profiile-dr-joohyung-lee/
www.hudson.org.au/profile-prof-vincent-harley/
Project Title How are male and female brains different?
Research Theme Neuroscience and Psychiatry
Main Supervisor Prof Vincent Harley [email protected] 8572 2527
Other Supervisors Dr Joohyung Lee [email protected] 85722 2507
Location Hudson Institute of Medical Research
Outline of project
Background: Male and female brains differ in anatomy, chemistry and behaviour. The
prevailing dogma that oestrogen is the key factor involved in brain sex differentiation was
challenged by our discovery of a direct role in the brain for the Y chromosome gene, SRY in
the control of voluntary movement, only in males.
Project Aims: This project seeks to identify the target genes that the SRY transcription factor
controls in the brain.
Techniques: Approaches include cell and molecular biology techniques (RNA seq, ChIPseq) and rodent dissection of the
substantia nigra.
Reading: Dewing P et al. Current Biology 16:415-20.; Czech D. et al. J Neurochem122:260-71. 2012 ; Czech D. et al.
Endocrinology155:2602-12 2014
Project Title Why is SRY A Risk Factor in men with Parkinson’s disease?
Research Theme Genetic Diseases
Main Supervisor Prof Vincent Harley [email protected] 8572 2527
Other Supervisors Dr Joohyung Lee [email protected] 85722 2507
Location Hudson Institute of Medical Research
Outline of project
Background: Parkinson’s disease (PD) is a debilitating neurodegenerative disorder,
triggered by the death of dopamine neurons in the brain region known as the substantia nigra.
Whilst the mechanisms underlying dopamine cell loss in PD, it is clear that males are more
susceptible to PD than females. We have identified that the male sex-determining gene SRY
directs a novel genetic mechanism of dopamine cell death in males. Understanding when and
how SRY increases the vulnerability of male dopamine neurons to injury will help explain
why males are more susceptible to the PD and to identify SRY as a novel target for
neuroprotectivetherapy in male PD patients.
Project Aims: This project seeks to determine how altering SRY levels can slow or halt the
progression of dopamine cell death and/or motor function.
Techniques: This project will use both in vitro and in vivo models of PD combined with molecular biology techniques (RNA
seq, ChIPseq) and rodent dissection of the substantia nigra.
Reading: Czech D. et al. J Neurochem122:260-71. 2012; Czech D. et al. Endocrinology155:2602-12 2014 ; Lee J. and
Harley V. Bioessays (6)454-7. 2012
2017 Anatomy and Developmental Biology Honours Projects Page 32
THE HUDSON INSTITUTE
Project Title The biological basis of gender identity
Research Theme Neuroscience and Psychiatry
Main Supervisor Prof Vincent Harley [email protected] 8572 2527
Other Supervisors Dr Fintan Harte (Monash Gender Clinic)
Location Hudson Institute of Medical Research
Outline of project
Background: Gender identity is the gender with which a person
identifies. Studies suggest that gender identity is affected by genetic,
prenatal hormonal or postnatal social determinants.
Project Aims: We are investigating the role of genes in patients with
gender identity disorders.
Techniques: This project involves undertaking genetic
association studies in the world’s largest cohort of male-to-female transsexuals. It focuses upon genes
involved in sex hormone synthesis and signalling.
Reading : Hare L. et al., Biological Psychiatry65(1):93-6and its commentary “Gender and the brain” Science,vol 322, p831
2017 Anatomy and Developmental Biology Honours Projects Page 33
MAIN SUPERVISORS AND PROJECTS
A/Professor Helen Abud
Page 7
Dr Minni Anko
Page 20
Professor John Bertram
Page 12
Professor Jane Black
Page 11
Professor John Carroll
Page 17
A/Professor Ann Chidgey
Page 23
Dr Luca Fiorenza
Page 19
Dr Quentin Fogg
Page 26
Professor Vincent Harley
Page 29
Dr Karla Hutt
Page 18
Professor Paul McMenamin
Page 25
Dr Brent Neumann
Page 24
Professor Moira O’Bryan
Page 15
A/Professor Roger Pocock
Page 16
Professor Gail Risbridger
Page 9
A/Professor Ian Smyth
Page 14
2017 Anatomy and Developmental Biology Honours Projects Page 34
Further information
A/Professor Craig Smith
Honours Co-Convenor
19 Innovation Walk
Level 3, Room 355
Phone: +61 3 9905 0203
Email: [email protected]
Dr Rob De Matteo
Honours Co-Convenor
Department of Anatomy and Developmental Biology
19 Innovation Walk
Level 3, Room 347
Tel:+61 3 9902 9108
Email: [email protected]
A/Professor Ann Chidgey
Honours Co-Convenor
15 Innovation Walk
Level 3, Room 314
Phone: +61 3 9905 0628
Email: [email protected]
facebook.com/Monash.University
twitter.com/MonashUni
www.med.monash.edu
Monash University reserves the right to alter information, procedures, fees and regulations contained in this document. Please check the Monash University website for updates
(www.monash.edu.au). All information reflects prescriptions, policy and practice in force at time of publication. Published July 2014. MM
S367275
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