Medicine, Nursing and Health Sciences Honours Projects 2017 · Enrolment in an honours project is subject to approval of the supervisor and the Honours Convenor. Closing dates for

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


A/Professor Ann Chidgey

15 Innovation Walk

Level 3, Room 314

Phone: 61 3 9905 0628

Email:[email protected]

http://www.med.monash.edu.au/anatomy/honours.html

http://www.sci.monash.edu.au/undergrad/honours/

http://www.med.monash.edu.au/biomed/honours/


https://www.monash.edu/science/current/honours

http://www.med.monash.edu.au/biomed/honours


mailto:[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.

http://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


Other Supervisors Dr Thierry Jarde,

Other Supervisors A/Prof Paul McMurrick (Cabrini Hospital)


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.



Project Title Functional Screening using intestinal organoids


Other Supervisors A/Prof Ron Firestein (Hudson Institute)

Other Supervisors Dr Thierry Jarde


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.



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




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



Project Title Defining epigenome changes in the tumour microenvironment





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





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


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]


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]


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



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]


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


Other Supervisors Prof John Bertram [email protected]


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.



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?


Other Supervisors A/Prof Ian Smyth [email protected]

Prof John Bertram [email protected]


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


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


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.



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


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.



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


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



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


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.



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]


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]


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).





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]


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.



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


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


Other Supervisors Dr Jan Kaslin [email protected] 9902 9613


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.



Project Title No nonsense – gene expression control in stem cells



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.



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]


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


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

[email protected]

[email protected]

9902-9182

9905-5550


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

http://www.med.monash.edu.au/anatomy/research/immune-regeneration.html

http://www.med.monash.edu.au/biochem/labs/lagruta-lab.html





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


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


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.


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.


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


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)


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.


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


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).


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.


EDUCATION FOCUSED

Project Title The Impact of Twitter on Developing Communities of Practice and Engagement


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.


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.


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



Project Title FGF signalling and sex reversal

Research Theme Genetic Diseases


Other Supervisors Dr Daniel Bird [email protected] 8572 2505


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


Other Supervisors Dr Monica Caggiano [email protected] 8572 2905


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.



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


Other Supervisors Dr Joohyung Lee [email protected] 85722 2507


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


Other Supervisors Dr Joohyung Lee [email protected] 85722 2507


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



Project Title The biological basis of gender identity

Research Theme Neuroscience and Psychiatry


Other Supervisors Dr Fintan Harte (Monash Gender Clinic)


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


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


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


Further information

A/Professor Craig Smith

Honours Co-Convenor

19 Innovation Walk

Level 3, Room 355

Phone: +61 3 9905 0203


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



Honours Co-Convenor

15 Innovation Walk

Level 3, Room 314

Phone: +61 3 9905 0628


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(www.monash.edu.au). All information reflects prescriptions, policy and practice in force at time of publication. Published July 2014. MM

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Medicine, Nursing and Health Sciences Honours Projects 2017 · Enrolment in an honours project is subject to approval of the supervisor and the Honours Convenor. Closing dates for