Cell-cell interactions in tumour progression - The University of Sydney

Pathology Discipline 

Honours Year Students 

Summary of Requirements

ENTRY REQUIREMENTS 

Must have a WAM of 65 or 

greater 

Must approach a supervisor 

obtain permission to 

undertake his/her Honours 

project

Why a WAM of 65 or greater? 

Faculty of Science rule that WAM must be >65 

The Faculty of Science may consider applicants in the 

range 63-65 on special application, with support from the 

Discipline 

WAM < 68 - difficult to achieve Honours 1 

The minimum score for Honours I is 80 

Pathology constrained by Faculty of Science (average Honours 

marks in each Dept must not exceed average WAM + 10). 

NOTE: The current cut-off for a post-graduate 

scholarship for a PhD is: 

WAM ~72/Hons ~82 (local students)

NOTE ! 

It is NOT necessary to have completed 

Cell Pathology 3.

REQUIREMENTS OF CANDIDATES 

General 

Recommended students start by February 1st. 

Courses: 

Animal Handling Course. 

Radiation Safety Course. 

Laboratory Safety Course


Seminars 

Department Presentations: 

Project overview & research plan 

March (10 min). 

Final seminar 

November (20 min) 

Weekly Research Techniques Seminars & 

Journal Club: - Semester 1 

Attendance at formal research seminars (x4).


Assessment 

Mark breakdown: 

Literature Review (May) 5% 

Final Seminar (Nov) 10% 

Thesis (Nov) 75% 

Coursework (Sem 1) 10% 

(Including all aspects of seminar 

participation)

How to apply for Honours 

Step 1: Select a research project/s. Lists of projects are available at 

this session and at: 

Pathology Discipline website: 

http://sydney.edu.au/medicine/pathology/students/honours/index.php 

Searchable database for Science Honours projects in the Faculty of Medicine: 

http://sydney.edu.au/medicine/future-students/honours/index.php 

Step 2: Discuss the research project with the supervisor/s and 

obtain permission to undertake the project/s 

Step 3: Submit application form to Pathology Discipline Front 

Office (Pathology Dept website) 

http://sydney.edu.au/medicine/pathology/students/honours/index.php 

Step 4: Submit application form to Faculty of Science 

http://sydney.edu.au/science/fstudent/undergrad/course/honours/index.shtml

Pathology Honours Website

Searchable database for Science Honours 

projects in the Faculty of Medicine 

http://sydney.edu.au/medicine/future-students/honours/index.php

Students considering Medicine 

or Dentistry 

It is possible and encouraged to defer 

admission into Medicine or Dentistry to 

undertake Honours (and later a PhD)

University of Sydney 

Honours Merit Scholarships 

Awarded on the basis of academic merit and 

personal attributes such as leadership and 

creativity 

$6,000 for one year ! 

Applications close early January 

http://www.usyd.edu.au/scholarships/prospective/honours.shtml

Marfan Syndrome (MFS) 

Hambly Lab 

Marfan syndrome (MFS) is an autosomal dominant inherited 

genetic connective tissue disease with the estimated 

incidence of 1 / 3000 ~ 5000. 

MFS patients are extremely tall and slim with multi-system 

symptoms. 

Skeletal: long slim limbs and fingers, scoliosis, pectus 

excavatum or carinatum and abnormal joint flexibility and 

so on. 

Ocular: ectopia lentis (most obvious symptom) 

Cardiovascular: mitral valve prolapse, ventricular 

dilatation and thoracic aortic aneurysm 

Possible pathogenesis 

MFS patients inherited an abnormal fibrillin mutation 

from their parents or may generate a new somatic 

mutation 

MFS patients produce abnormal fibrillin, compromising 

microfibril formation 

Fibrillin-1+ latent TGF-β → control TGF-β signalling 

21 May 2012

Abnormal elasticity 

- STIFF WALL (echo) 

Abnormal fibrillin 

Excessive wall stress 

during heart pumping 

Inflammation 

- cytokines 

- MMPs 

Cystic Medial Necrosis 

Thoracic aortic aneurysm 

Failure of sequestration of TGF-β 

- Increased fibrosis 

- STIFF WALL (echo) 

21 May 2012

Plasma TGFβ and MMPs in Human Heritable Aortopathy 

600 

400 

200 

15 

10 

5 

0 

0 

TGFβ ng/ml x 10 NS 

Control Marfan MASS FTAD 

MMP3 (ng/ml) 

* 

Control Marfan MASS TAAD 

* 

600 

400 

200 

0 

150 

100 

50 

0 

MMP2 ng/ml 

* 

Control Marfan MASS FTAD 

MMP9 (ng/ml) 

Control Marfan MASS TAAD 

Lu et al unpublished data 2012 

* 

NS

Supervisor: Dr Danuta Kalinowski 

Co‐Supervisor: Prof Des Richardson

Fe 

Oxidative Phosphorylation DNA Synthesis 

‐ Cancer cells require higher levels of iron for proliferation and are 

more sensitive to iron depletion than normal cells.

• Therefore, drugs that can bind iron (iron chelators) 

represent a novel chemotherapeutic treatment avenue.

Vehicle Control 

(15% Propylene 

glycol in Saline) 

Dp44mT 

(0.4 mg/kg) 

SK-Mel-28 Tumour Implants after 7 weeks of Treatment – IV injection once a day

• This project will assess the anti‐cancer activity and 

the mechanisms of action of novel iron chelators 

developed in our group. 

‐ Structure‐Activity Relationships 

‐ Pharmacology 

‐ Routes of Cellular Uptake 

‐ Selectivity in Targeting Cancer

Ascorbate 

Iron Metabolism & Chelation (IMC) Program 

Department of Pathology 

The University of Sydney

Iron (Fe) is an essential metal for all mammalian 

cells 

Fe is required for oxygen transport, mitochondrial 

respiration, DNA synthesis, etc. 

Although necessary, Fe is potentially toxic to cells 

and must be carefully delivered 

Almost all Fe in plasma is bound to the serum Fe 

transport protein, transferrin (Tf) 

The Tf‐to‐cell cycle is the major Fe uptake route 

used by most cells, and in particular during red 

blood cell production 

The following honours project examines some 

basic unanswered questions in cellular Fe biology

Andrews N C Blood 2008;112:219-230

Transferrin-Fe 

complex 

Cell 

Transferrin 

without Fe 

•Cells in the body take up 

almost all their iron (Fe) 

from the transferrin (Tf)-tocell 

cycle 

•Vitamin C (ascorbate) 

stimulates this process by 

an unknown mechanism

•Cells in the body take up 

almost all their iron (Fe) 

from the transferrin (Tf)-tocell 

cycle 

•Vitamin C (ascorbate) 

stimulates this process by 

an unknown mechanism 

•The Tf-to-cell cycle can 

be regulated by hypoxiainducible 

factors (HIFs) 

•Your project can 

examine how ascorbate 

regulates cell Fe uptake 

via HIFs.

Relevance to understanding basic cellular 

and systemic iron metabolism, which is 

central to a wide range of disease types. 

Relevance to cancer cell metabolism as the 

metabolic phenotype in cancer cells is 

frequently associated with increased 

expression of HIF1α and decreased cellular 

ascorbate

Please contact either: 

Darius Lane 

darius.lane@sydney.edu.au 

Des Richardson 

d.richardson@sydney.edu.au

N 

Iro on 

N 

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DpC 

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N 

HO O 

Me etaboolismm 

aand 

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Che C elat tion n PPro 

ograamm 

HHO 

ONO OUR RS S PRROOJE 

ECTTS 

Hea aded bby: 

Profes P ssor Des D Riicharddson 

H 2 

O 

H O 

N 

(CH2 ) 5 

N 

HO O 

DFO 

H 

N 

(CH ) 2 5 

N 

HO O

Iron is essential for f life and gr rowth. While it is well kno own that ironn 

deficiency ccan 

lead to annaemia 

it is geenerally 

not 

appreeciated 

that iron i is critica al for the grow wth of all cell ls, particularlly 

cancer cell lls. The Iron MMetabolism 

aand 

Chellation 

Progra am is concern ned with unde erstanding the 

basic proceesses 

of how ttumour 

cells utilise and trransport 

iron. 

This knowledge will w lead to the 

developmen nt of therapie es that can seelectively 

starrve 

tumour ceells 

of iron annd 

inhibit 

theirr 

growth. In addition, a we are a studying the t mechanis sms involved in iron loadinng 

in the inhherited 

diseasees 

β- 

thalaassaemia 

and d Friedreich's s ataxia. 

1. Deevelopment 

t of New Iro on Chelators s as Novel Drugs D Againnst 

Cancer 

Primmary 

supervis sor: Prof. Des 

Richardson; 

Co-supervi isors: Dr. Davvid 

Lovejoy, Dr. Danuta KKalinowski. 

This project will use u a combina ation of techn niques that are e implemented 

in chemistrry, 

biochhemistry, 

phy ysiology, mole ecular biology y and pharma acology to dessign 

and asseess 

the activityy 

of noovel 

drugs for r the treatmen nt of cancer. Your Y project will w be multi- faceted and wwill 

involve 

growwing 

human tu umour cells in n tissue cultur re and assessi ing the effectss 

of chelators on gene 

expreession. 

This will w be done using u Western n analysis, RT T-PCR and mmicroarray 

anaalysis. 

The labb 

has cconsiderable 

experience e in these cutting g-edge techniq ques and you will be taughht 

the 

intriccacies 

of their r use. Feel fre ee to contact Dr. D David Lov vejoy (david. lovejoy@syddney.edu.au) 

and DDr. 

Danuta Kalinowski 

(da anutak@med. .usyd.edu.au) to have a chaat 

about whetther 

the projecct 

matches yoour 

interests. 

2. Tra ansport of nitric n oxide in cells andd 

its interacttion 

with iroon 

conta aining proteins 

in tumoour 

cells 

Prima ary superviso or: Prof. Des Richardson. 

Nitric oxide (NO) functions f as a natural iron chelator and is often secreeted 

by 

macro ophages to des stroy cancer ccells. 

This prooject 

involvess 

examining tthe 

method by y 

which NO is able to o induce the ssecretion 

of irron 

from canccer 

cells. Thiss 

project will 

use a combination c of o techniquess 

that are usedd 

in biochemistry, 

physioloogy, 

cell 

biolog gy, molecular biology and ppharmacologgy. 

Feel free too 

contact Prof. 

Des 

Richar rdson (d.richa ardson@med. .usyd.edu.au) ) to have a chat 

about whetther 

the 

projec ct matches you ur interests. 

3. Thhe 

Role of Iron I in the Pathogenesi 

P is of the Cri ippling Neurrodegeneraative 

Diseasee, 

Friedreichh's 

Ataxia 

Primmary 


Richardson; 

Co-supervi isors: Dr. Micchael 

Huang, Dr. Yohan SSuryo 

Rahmannto. 

Frieddreich’s 

Ataxi ia is a neurod degenerative disease d cause by the accummulation 

of iroon 

in the enerrgy 

produucing 

macrop phages. This condition c ofte en results in cardiac c hyperttrophy, 

muscuular 

atrophy aand 

earlyy 

death. The current c project t will examin ne both the pat thophysiologgy 

of Friedreicch’s 

ataxia annd 

a 

potenntial 

new ther rapy that invo olves iron chelation. 

This project will use u a combina ation of techn niques that are e used in biocchemistry, 

phyysiology, 

pharmmacology 

and d molecular biology. b Feel free f to contac ct Dr. Michaeel 

Huang 

(mihuuang@med.u 

usyd.edu.au) to t have a chat t about wheth her the projectt 

matches youur 


4. MMolecular 

Re egulation of f eIF3a in Cancer C Cell Motility M andd 

Invasion 

Primmary 


Richardson; 

Co-supervi isors: Dr. Fedderica 

Saletta. 

eIF3a is the largest su ubunit of the eeukaryotic 

iniitiation 

factorr 

3 (eIF3) andd 

plays a role 

as a regu ulator of a sub bset of mRNAAs 

encoding pproteins 

invollved 

in the cell 

cycle, cell 

prolifera ation and cell mobility. Thiis 

project aimms 

to identify new targets oof 

eIF3a 

involved d in enhanced cancer cell mmobility 

and iinvasion. 

A vaariety 

of techhniques 

will 

be used including: i cel ll culture, revverse-transcripptase-PCR 

annd 

quantitative 

PCR, 

Western blotting, imm munofluorescent 

staining, ggene 

knockdoown, 

drug treeatment 

etc. 

This study is impo ortant for und derstanding th he pathologica al role of eIF33a 

in the exprression 

of mettastasis 

regulaators 

and for 

develloping 

novel therapeutics targeting t eIF3 3a and its dow wnstream signnaling. 

Our sttudies 

are cruucial 

for deepeening 

our 

knowwledge 

about cancer cell bi iology and de eveloping exp ploitable treatmments 

for canncer. 

Feel freee 

to contact DDr. 

Federica 

Salettta 

(fsaletta@med.usyd.edu 

u.au) to have a chat about whether w the pproject 

matchhes 

your intereests.

5. Innvestigating 

g cellular res sponse to iron-depletion 

by examinning 

the miitogen-activated 

proteinn 

kinases 

(MAAPK) 

signall ling pathwa ay 

Primmary 


Richardson; 

Co-supervi isors: Dr. Yu Yu. 

Iron-depletion 

ca an cause mmultiple 

effeccts 

includingg 

inhibition of the iron n- 

IRON DEPLETION 

containing 

enzym me, ribonuclleotide 

reduuctase 

whichh 

is importaant 

for DNA A 

TTrx 

Trx 

synth hesis, cell cyc cle arrest andd 

apoptosis. RRecently, 

the rrole 

of signalling 

pathways 

AASK1 

ASKK1- 

P 

in th he regulation of cellular iroon 

metabolismm 

is becominng 

increasinglly 

recognized d. 

The aim of this pr roject is to eluucidate 

the mmolecular 

signnalling 

pathwaay 

involved in n 

MKK4/7 

MKK3/6 

iron-depletion 

by y examiningg 

the mitogeen-activated 

protein kinaases 

(MAPK K) 

DUSPP 

1 

DDUSP 

1 signa alling pathwa ay which funcctions 

to link extracellularr 

signals to regulate 

diverse 

DUSPP 

10 

DUSPP 

16 

JNK- P 

p38- P DDUSP 

10 

DDUSP 

16 cellu ular processes. 

The projeect 

will invollve 

multiple techniques iincluding 

cel ll 

cultu ures, RNA tr ransfection, rreverse-transccriptional-PCCR, 

Western blotting, cel ll 

p53- P 

ATF2- P proli iferation assa ays, etc. The rresults 

will bee 

vital for ouur 

understandiing 

of cellula ar 

signa alling aspect ts of iron-deficiency 

and d the molecuular 

pharmacoology 

of iron n 

APOPTOSIS 

chela ation. Contac ct Dr. Yu Yuu 

(yuyu@medd.usyd.edu.auu) 

to have a cchat 

about the 

proje ect. 

HS 

HS 

S 

S 

6. Cancer 

Thera apeutics and 

Targeting g (Multi-Dru ug Resistannce) 

Primmary 

supervis sor: Dr. Patri ic Jansson; Co o-supervisor rs: Prof. Des RRichardson. 

Multtidrug 

resistan nce (MDR) is a phenomeno on in which cancer c cells arre 

resistant too 

the cytotoxicc 

effects of vaarious 

chemmotherapeutic 

agents. One major mechan nism by whic ch this occurss 

is through thhe 

over--expression 

of 

ATP-dependent 

drug effl flux transporte ers such as thhe 

P-glycoprottein 

(Pgp) ) and multidrug 

resistance-associated 

pr rotein (MRP) ). The hypoxiia-inducible 

fa factor 

(HIF)-1 

is a maste er transcriptio onal activator of oxygen-re egulated geness 

and HIF-1 iis 

consttitutively 

up regulated r in several 

tumou ur types under r hypoxic connditions 

and HHIF 

mighht 

thus be imp plicated in tum mour therapy resistance. 

This Honours proj ject will investigate 

wheth her iron chelat tion, HIF-1 acctivation, 

hyppoxia 

and PPgp 

is important 

for how novel n iron che elators overco ome drug resisstance. 

This project will use u a combina ation of cuttin ng-edge techn niques includiing: 

cell cultuure, 

westeern 

blotting, siRNA, s cytoto oxicity detect tion and fluor rescent/confoccal 

microscoppy 

etc. PPlease 

contact t Dr. Patric Ja ansson (patric c.jansson@sy ydney.edu.au) to discuss thhis 

projeect. 

7. Thhe 

Role of Melanotrans 

M sferrin in Melanoma M Growth G and Metastasis 

Primmary 

supervis sor: Dr. Yoha an Suryo Rah hmanto; Co-su upervisors: PProf. 

Des Ricchardson, 

Dr. Yu Yu, Dr. ZZaklina 

Kovaacevic. 

Melaanoma 

is the fourth f most co ommon cance er in NSW an nd Australia aand 

new 

Iron homeostasis / 

metabolism 

treatmments 

are urg gently required. 

Melanotran nsferrin (MTf f) is a molecuule 

that is 

highlly 

expressed in i melanoma (for review see 

Oncogene 26:6113-24) . The 

Epithelial septal 

Angiogenesis 

MTf 

junction 

aim oof 

this project t is to examin ne the hypothe esis that MTf f plays roles inn 


cyclee 

progression, , growth and melanoma m me etastasis. This 

is importantt 

as 

Cell prroliferation, 

migration and 

tumourigenesis 

melaanoma 

inciden nce is increasi ing worldwid de and metasta atic melanomma 

is 

almoost 

completely y resistant to every e known therapy. Laboratory 

technniques 

involveed: 

animal haandling, 

mammmalian 


cultuure, 

molecular r cloning, cell l transfection, , RNA and pr rotein extractiion, 

RT-PCR, 

Western blootting, 

cell bioology 

assay 

and aanalysis, 

flow w cytometry an nd immunohi istochemistry. 

Contact Dr. Yohan Suryoo 

Rahmanto 

(yohaan.suryorahm 

manto@sydney y.edu.au) to have h a chat ab bout this projeect. 

8. MMolecular 

regulation 

of ERp29 in epithelial 

can ncer cell plaasticity 

Primmary 

supervis sor: Dr. Daoh hai Zhang; Co o-supervisor rs: Prof. Des RRichardson 

Endooplasmic 

retic culum protein n 29 (ERp29) is a novel mo olecule that innduces 

epithelial-mesenchyymal 

reverse transition and d 

epithhelial 

cell mor rphogenesis. This T project aims a to understand 

the funcctions 

and moolecular 

mechhanisms 

of ERRp29 

in 

estabblishing 

epithe elial architect ture in cancer r cells. A variety 

of techniqques 

that will be used incluude 

cell cultuures, 

3- 

dimeensional 

cell system, s revers se-transcriptio onal-PCR, Western W blottinng, 

immunofluuorescent 

staiining, 

proteinn-protein 

interaaction, 

gene knockdown, k etc e . This stud dy is importan nt for understaanding 

the paathological 

fuunction 

of ERpp29 

as a 

noveel 

tumour supp pressive mole ecule and for developing novel n therapeuutics 

targetingg 

ERp29 and its downstreaam 

signaling. 

1

9. Diissecting 

the e role of NDR RG-1 in regu ulating endo oplasmic retiiculum 

stress 

and cancerr 

cell survivaal 

Primmary 

supervis sor: Dr. Daoh hai Zhang; Co o-supervisor rs: Prof. Des RRichardson. 

N-myyc 

downstrea am regulated gene g 1 (NDRG G1) is a meta astasis suppressor 

that is 

invollved 

in cell di ifferentiation, , carcinogenesis, 

survival, and metastasis. 

It is sensittive 

to thee 

redox status s of the cells and a the intrac cellular calciu um concentrattion. 

Disruption 

of caalcium 

homeo ostasis within endoplasmic reticulum (E ER) system is associated wiith 

the EER 

stress response 

that repr resents an ada aptive mechan nism supporti ting survival aand 

chemmoresistance 

of o tumor cells s. This project t aims to disse ect how NDRRG1 

expressioon 

moduulates 

ER stre ess and to und derstand the biological b con nsequences. TThis 

study willl 

use 

cell cculture, 

immu unoblotting, gene g silencing g, cell-based functional f anaalysis, 

phospphatase 

assay y, drug treatm ment and cell apoptosis, a etc. 

Feel free to contact Dr. 

Daohhai 

Zhang (da aohai.zhang@ @sydney.edu.a au) to have a chat c about thiis 

project. 

10. HHow 

does vi itamin C (as scorbate) re egulate iron n uptake by cells? The rrole 

of HIFss. 

Primmary 

supervis sor: Dr. Dariu us Lane; Co- supervisors: Prof. Des Riichardson. 

Iron (Fe) is essen ntial for life and it has long l been re ecognised thaat 

vitamin C (ascorbate)- deficiency caauses 

anemia a. 

Normmally, 

circulating 

Fe is bou und to the Fe e-binding protein, 

transferrrin 

(Tf), withh 

Tf-Fe uptakke 

being the mmajor 

route of o 

Fe uuptake 

by ma ammalian cells. 

Cellular hypoxia h (low w oxygen tenssion) 

stimulaates 

Tf-Fe upptake 

by up-rregulating 

the 

expreession 

of proteins 

involve ed in the classical 

Tf-to-ce ell cycle for FFe 

delivery ( (e.g., the Tf rreceptor; 

TfRR1). 

We have 

recenntly 

identified d that ascorb bate, which is s abundant in n vivo but typpically 

absent nt in standardd 

cell culture, 

dramatically y 

stimuulates 

Fe upta ake from Tf-F Fe, although th he molecular mechanism iis 

unknown. 

The aim of this project p is to determine d ho ow ascorbate interacts i withh 

HIFs to reggulate 

cellularr 

Fe uptake. TThis 

will have 

impoortant 

ramifica ations for the treatment of f diseases rang ging from anaaemia 

to canccer. 

Feel free to contact Drr. 

Darius Lane 

(dariuus.lane@sydn 

ney.edu.au) to o have a chat about whethe er the project matches youur 


11. HHow 

do astr rocytes proc cess iron? Role R of GPI-linked 

Cp. 

Primmary 

supervis sor: Dr. Dariu us Lane; Cosupervisors: Prof. Des Riichardson. 

The bbrain 

has a high 

requirement 

for iron (Fe), ( which is s essential forr 

life, yet the mechanisms by which Fee 

enters and is 

proceessed 

by the brain b remains s a mystery. Within W the bra ain, astrocytes 

(‘star-shapeed’ 

glial cells that are at leeast 

equivalen nt 

in nuumber 

to neur rones) are tho ought to be important i in processing p annd 

re-distribuuting 

Fe in thhe 

brain. Astrrocytes 

extend d 

long processes that 

ensheathe the brain cap pillaries and help to form m the BBB. Inntriguingly, 

thhe 

ends of thhese 

processes 

(i.e., the ‘end-feet t’) express a special s form of o the Fe oxid dising enzymme, 

ceruloplasmmin 

(Cp). Thhis 

protein is ttethered 

to the 

exterrnal 

surface of o the plasma membrane by b a glycopho osphatidylinossitol 

(GPI) annchor. 

The roole 

of astrocyyte 

GPI-linked d 

Cp iss 

unknown. 

The aim of this project p is to determine the 

role of GPI I-linked Cp inn 

astrocytic FFe 

processingg. 

This will hhave 

importan nt 

ramiffications 

for the t understan nding and trea atment of neu urodegeneratiive 

diseases tthat 

are assocciated 

with abbnormal 

brain n 

Fe metabolism, such as Alzheimer’s A 

and Parkin nson’s diseaases. 

Feel free to coontact 

Dr. Darius Lane 

(dariuus.lane@sydn 

ney.edu.au) to o have a chat about whethe er the project matches youur 


12. EExamining 

the t Molecul lar Mechanisms 

Behind d the Anti-TTumour 

Acttivity 

of NDDRG1 

in Panncreatic 

Cancer 

Primmary 


Richardson; 

Co-supervi isor: Dr. Zakllina 

Kovacevvic. 

Pancreatic 

cancer is a highly ag ggressive dise ease with a po oor response tto 

current 

theraapies. 

The metastasis 

suppr ressor N-myc c down-stream m regulated geene 

1 (NDRGG1) 

has bbeen 

shown to o effectively inhibit i pancre eatic cancer by y reducing prrimary 

tumouur 

growwth, 

metastasis s and angioge enesis. 

This project will involve 

exami ining the mol lecular functio ons of NDRGG1 

to elucidatte 

the 

mechhanisms 

that are a involved in i its anti-tum mour activity. Moreover, thhe 

project will 

also 

exammine 

a novel class c of anti-cancer 

agents that are able to t markedly uup-regulate 

NDRRG1 

expressio on in cancer and a may be a potential new w therapeutic strategy for 

pancrreatic 

cancer treatment. 

A rannge 

of experim mental techni iques includin ng tissue cultu ure, western bblot 

analysis, 

immuunohistochem 

mistry and dru ug treatments will be performed. 

Feel frree 

to contact Dr. 

Zakliina 

Kovacevic 

(zaklina.kov vacevic@syd dney.edu.au) to t have a chatt 

about whethher 

the 

projeect 

matches yo our interests.

2013 Honours Projects 

SYDNEY MEDICAL SCHOOL 

Neuropathology 

Dr Greg Sutherland and Prof Jillian Kril 

Discipline of Pathology

Alcohol-related brain damage 

and neurogenesis 

Sutherland et al. Submitted to Exp Neurol 

Fluorescent 

microscopy 

ARBD and Hepatic Encephalopathy 

Human brain transcriptome 

2

Dementia 

Alzheimer's disease Frontotemporal dementia 

Sutherland and Kril. Ch 16, Neuroscience: Dealing with Frontiers 

Masters CL, Kril JJ et al. Pathology 2011;43:93-102. 

Neuroglobin, PI3K/Akt 

signaling and Alzheimer's 

disease 

3

2013 Honours Year Project: 

Cell-cell interactions in tumour progression 

Dermatology Research Labs, Blackburn Bldg 

Principal supervisor: Assoc. Prof. Guy Lyons 

guy.lyons@sydney.edu.au 

Associate supervisors: Dr Cathy Payne 

Dr Vani Raviraj 

Prof. Gary Halliday


• Mutations cause two basic properties of cancer: 

• Uncontrolled proliferation 

• Spread from the site of origin 

• Tumours often contain cells that have different mutations 

i.e. they are distinct clones 

• This genetic diversity provides the opportunity for 

interactions to occur between clones 

• Clonal interactions might make tumours more malignant 

BUT DO THEY? 

Aim: Create clones with distinct oncogenes and 

test their malignant behaviour alone and together


Techniques used: 

1. Genetic engineering 

2. Genetic modification of cultured mammalian cells 

3. Analysis of gene expression immunologically 

4. Fluorescence microscopy 

5. Small animal handling and bioimaging

Engineer gene expression vectors 

Use molecular biological methods to make plasmid and viral 

vectors suitable for expressing genes in mammalian cells

Make genetically modified human cell lines 

Transfect the starting non-malignant clone 

with candidate oncogenes 

Gene 1 

+ 

RFP 

Clone 1 Clone 2 

Clones 1 and 2 

together 

Proliferation * Motility * Invasion * Tumour Growth

Live cell imaging microscopy to measure 

cell motility

Live animal imaging to measure 

tumour growth 

Paul Sou

2013 Honours Year Project: 


Dermatology Research Labs, Blackburn Bldg 

Principal supervisor: Assoc. Prof. Guy Lyons 

guy.lyons@sydney.edu.au 

Associate supervisors: Dr Cathy Payne 

Dr Vani Raviraj 

Prof. Gary Halliday

Redefining the role of monocytes/macrophages in vascular disease 

Are all macrophages in the plaque bad? 

Thin cap 

(mac MMPs) 

large 

necrotic core 

(mac foam cells) 

the 

Heather Medbury, Vascular Biology Research Centre, 

Surgery, Westmead Hospital, Westmead 

Heart attack 

stroke

Classical activation M1 Alternatively activated M2( a, b, c...) 

CD86 

CD64 CD163 

Plaque instability? 

M1:CD86 M2:CD163 

CD206 (MR) 

Athero‐protective? 

Macrophage marker, procollagen I, co‐expression mac marker & procollagen I, nuclei

Redefining monocyte/macrophage role by addressing: 

SMC 

1. Site of transformation: (blood or plaque) 

MMP’s 

4. Fate of the cell: 

Proliferation, death, migration 

3. Function 

‐Foam cell 

‐MMPs 

‐Collagen 

production 

2. Pathway of differentiation (including plasticity) 

EC

Dr Hilda Pickett 

hpickett@cmri.org.au 

Cancer Research Unit 

http://www.cmri.org.au

Telomere biology group 

Cancer cells become 

immortal by activating 

the enzyme telomerase 

to replenish telomere 

loss during cell division

Telomere maintenance mechanisms in cancer 

Projects available: 

1. Molecular changes associated with the alternative lengthening of 

telomeres (ALT) mechanism of telomere maintenance 

2. The role of telomere rapid deletion in cell proliferation 

3. Functional analysis of single nucleotide polymorphisms within the TERT 

locus 

4. The role of non-coding RNAs in telomere maintenance mechanisms 

hpickett@cmri.org.au

Defining the antigen presentation capacity of brain endothelial cells 

Primary supervisor: Dr Julie Wheway (julie.wheway@sydney.edu.au) 

Co‐supervisor: Prof Georges Grau (georges.grau@sydney.edu.au) 

Techniques used will include cell culture, tripartite co‐culture assays, flow cytometry and fluorescence 

microscopy. 

pRBC 

“Professional” 

APC 

Brain endothelial cells 

Immature 

T cell 

? 

Activated 

T cell

Examining an immunomodulatory role for endothelial microparticles 

Primary supervisor: Dr Julie Wheway (julie.wheway@sydney.edu.au) 

Co‐supervisor: Prof Georges Grau (georges.grau@sydney.edu.au) 

Techniques used will include cell culture, flow cytometry and fluorescence microscopy and western 

blotting. 

pRBC 

Inflammation 

Brain endothelial cells 

Membrane surface 

shedding 

eMPs 

? 

Immature 

T cell 

Activated 

T cell

Nature Genetics Cell 

American Journal of Human Genetics 

Human Molecular Genetics 

Sports Illustrated 2010 

A gene for speed: the 

role of α-actinin-3 in the 

regulation of skeletal 

muscle mass 

Supervisors: Professor Kathryn 

North, Dr Kate Quinlan and Dr 

Peter Houweling

WT KO 

kate.quinlan@sydney.edu.au 

~ 1 billion people

Located in Westmead Millennium Institute 

Currently have 3 grants 

Supported by the Storr Trust 

Westmead pulls in 1/3 of NHMRC funding going to USYD 

My group is 10: 1 Postdoc, 4 PhD students, 4 RAs, 1 TA. 

Have 20 knock‐out mouse lines available 

Looking for students to do Honours and then a PhD 

New Building in March 2014

Does liver talk to fat?? 

Eg: 

Adiponectin 

TNF, IL6 

FABP4 

?????? BA 

Metabolic Studies using TGR5, FXR & Adiponectin KO mice

Does diet promote adipocytokine changes?

Skills learned 

1. Cell based models 

2. Mouse based models. 

3. Biochemistry, histology. 

4. Human cohorts. 

lionel.hebbard@sydney.edu.au 

Phone: 02 9845 9132

Most common inherited 

disease presenting in 

neurogenetics clinics 

Clinically and genetically heterogeneous 

disorder affecting both the motor and 

sensory neurons of peripheral nervous 

system 

CHARCOT MARIE 

TOOTH DISEASE (CMT) 

50 Genes known to cause CMT 

The biological problem is the 

‘dying back’ of the nerve or 

axonal degeneration

Family Studies & Linkage Analysis 

Utilising Exome SequenceData 

Bioinformatics 

IDENTIFYING 

NEW GENES 

CAUSING 

MOTOR 

AND SENSORY 

NEURON DEATH 

International Track record 

State-of-the-art technology for 

variant validation 

High Resolution 

Melt (HRM) 

Well resourced lab – staff & students

Westmead Millennium Institute 

Dr Mark Douglas 

Hepatitis C Virus 

Pathogenesis Group 

for Medical Research

Hepatitis C Virus (HCV) 

› 3% of the world’s population (1% in Australia) is infected with HCV 

› It is now the main cause of liver failure, liver transplant and liver cancer in 

Australia, USA and UK 

› HCV causes more deaths than HIV in Australia and USA 

› It is now curable but current treatments are toxic and often fail, so new 

treatments are needed 

2

Metabolic Complications of Hepatitis C 

HCV interacts with Host Lipid Metabolism 

› Steatosis (fatty liver) – HCV Genotype 3 

- Lipids essential for HCV replication 

- Virus circulates in serum with lipoproteins 

- Block lipid synthesis inhibits HCV replication 

› Insulin resistance (diabetes) – Genotype 1 

- Faster progression to liver fibrosis, 

cirrhosis and liver cancer 

- Predicts non-response to antiviral treatment (interferon, 

ribavirin) 

› Mechanisms are poorly understood 

3

PROJECT 1 

Treating hepatitis C virus with cannabinoid antagonists 

› Endocannabinoids are hormones related to cannabis that control lipid 

metabolism 

› CB1 is the main endocannabinoid receptor in the liver 

› CB1 expression is increased in the livers of people with chronic hepatitis C 

- This likely contributes to steatosis and encourages virus replication 

› Drugs that block CB1 (CB1 antagonists) can inhibit HCV replication in cell 

culture models. 

› This project explores the mechanism of this effect, and will hopefully lead 

to trials of CB1 antagonists in patients with Hepatitis C 

4

PROJECT 2 

Reversing IFN refractoriness to improve HCV treatment 

› The main treatment for HCV is interferon (IFN) alpha 

- Over 50% of patients with HCV genotype 1 fail current IFN treatment 

› Patients who respond poorly to IFN have evidence of IFN pre-activation in 

their liver, which induces IFN refractoriness and poor response to IFN 

› We have discovered novel proteins that inhibit IFN signalling in patients 

with hepatitis C infection 

› We have shown that PPAR alpha agonists (anti-cholesterol drugs) can 

partially reverse IFN refractoriness in HCV cell culture models 

› This project will explore the mechanisms of this effect, and will hopefully 

lead to trials of these drugs in patients with chronic Hepatitis C 

5

› Contac Mark Douglas 

› Mark.douglas@sydney.edu.au 

› Tel: 9845-7705 

6

Change 

Sensitive Resistance 

Supervisor: 

Dr. Patric J. Jansson 

Cancer Therapeutics and Targeting Group, 

Iron Metabolism and Chelation Program 

Problem 

Project: How to overcome MDR?

Supervisor: Paul K. Witting (Pathology) 

E-mail: pwitting@med.usyd.edu.au 

Phone: 9767-9103 

Discipline of Pathology 


1

Redox Biology Lab 

• Research team comprises 1 PTE Postdoctoral 

Fellow, five Postgraduate students (3 x PhD and 2 x 

MPhil), one PTE Research assistant, and facility for 

a maximum of two Honours students (2013) 

Technical expertise 

• Field of redox biology coupled with monitoring of 

oxidative stress in developing vascular disease 

2

Animal study 

Research Projects 

• Title: Post translational changes to key cardiac proteins in the 

hearts of diabetic rats after experimental heart attack 

Cell-based studies 

• Title: Achieving neuro-protection by increasing neuronal cell 

content of neuroglobin. 

• Title: Snore-like vibrations stimulate a pro-inflammatory and 

prothrombotic state in endothelial cells 

3

Model of experimental AMI in rats 

The left anterior descending 

(LAD) coronary artery is ligated 

to simulate AMI 

Blood flow is inhibited to this 

region of the myocardium for 30 

min (ischemia). 

Release of the suture simulates 

tissue reperfusion. 

4


Outcomes of sleep 

studies in infants: 

Obstructive Sleep Apnea 

(OSA) & CPAP use. 

Dr Rita Machaalani & Prof Karen Waters 

SIDS & Sleep Apnea Laboratory 

Side effect of OSA 

=daytime sleepiness 

Treatment= (continuous positive 

airways pressure (CPAP) machine

Project title: Phospho‐regulation of centrosome proteins in cancer cells 

Supervisors: Dr Rose Boutros 

Dr Megan Chircop 

Laboratory: Cell Cycle Unit 

The Children’s Medical Research Institute 

Westmead 

The centrosome 

Structural proteins: ‐, ‐, ‐tubulins, Centrins, Pericentrin, Ninein, Nucleophosmin, CP110,... 

Regulatory Proteins: CDKs, Cdc25, PLK, Nek2, PP2A, 14‐3‐3, dynein, dynactin, Mps1, ...

The Project 

A study in S. Cerevisiae revealed that the majority of yeast centrosome proteins are 

phosphorylated at some stage during cell division Keck et al. Science 332:1557, 2011 

Hypothesis: Phosphorylation of centrosome proteins is important for normal 

centrosome function and cell division in human cells. 

Misregulation of these can contribute to cancer. 

Aims: Investigate the role of protein phosphorylation in regulating centrosome 

function in cancer 

‐ mutate phosphorylation sites by site‐directed mutagenesis 

‐ introduce phosphorylation mutants into cells and screen for 

phenotypes using immunofluorescence microscopy

E‐cadherin 

B‐catenin 

Deciphering the function of NDRG1 

Primary Tumour 

A number of molecular changes 

occur in the cell including: 

‐E‐cadherin is reduced 

‐B‐catenin is reduced 

These molecules are crucial for 

cell adhesion and motility. 

E‐cadherin 

B‐catenin 

NDRG1 

Change in Morphology to 

become more invasive 

NDRG1 can REVERSE this! 

Control NDRG1 

Control NDRG1 

NDRG1 restores the expression 

of crucial molecules that 

promote cell adhesion and 

inhibit cell motility. 

Cancer Metastasis 

HOW DOES 

NDRG1 DO 

THIS??? 

Perhaps YOU will be 

able to find out!!! 

Contact: 

Dr. Zaklina Kovacevic 

zaklina.kovacevic@sydney.edu.au

2013 Honours Projects in 

Cardiovascular & Hormonal Research Laboratory 

Susie Mihailidou - anastasia.mihailidou@sydney.edu.au 

Level 13, 

Kolling Institute of Medical Research, 

Royal North Shore Hospital 

Honours student 

PhD student 

Medical student – Elective term 

2 Research Fellows 

Royal North 

Shore Hospital

Occluding branch of LAD 




Experimentally simulate a heart attack 

Reperfusion Injury 

Free radicals 

Stress-response 

Apoptosis 

Autophagy 

Non-ischemic areas 

Cardiac damage 

Royal North 

Shore Hospital 

Infarct 

area 

At- risk but viable

For 2013: 

• Regulation of aldosterone/mineralocorticoid receptors in the heart 

• Glucagon-Like Peptide-1 agonists, reperfusion injury and type 2 diabetes 

• Hyperglycemia Removes the Gender Gap During Experimental Myocardial 

Infarction 




Royal North 

Shore Hospital

Cell-cell interactions in tumour progression - The University of Sydney

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