Student Opportunities

Oncology Research Unit

Background information

The Oncology Research Unit (ORU) at The Children's Hospital at Westmead is carrying out both basic and translational research to improve knowledge of the biological basis of cancer and to improve the diagnosis and treatment of cancer. The Unit is making significant and internationally recognised advances in understanding the molecular and structural basis of cancer using techniques ranging from gene discovery to cell culture and whole animal models. Projects undertaken are frequently collaborative and are strengthened by our location within a paediatric teaching hospital and the close relationship with the clinical oncology and pathology departments.

The ORU is affiliated with the University of Sydney through the Discipline of Paediatrics and Child Health and also has links to other Departments within both the Medical and Science Faculties. The Unit has excellent opportunities for students with a variety of projects and programs to suit PhD, Masters, Honours and Vacation Students. Projects are outlined below and are identified if specifically designed for a predetermined duration or level of research experience eg. Honours Student Project.

The ORU is committed to advancing cancer health care through excellence in basic, clinical and translational research. A limited number of departmentally funded scholarships or stipend enhancement grants are available depending on undergraduate record and research experience. Students are also encouraged to pursue external peer-reviewed scholarships.

Contact

Interested students should contact Janett Clarkson for general enquiries regarding the currently available student opportunities within the Oncology Research Unit.

Janett Clarkson
Research & Development Manager
Oncology Research Unit
Email: janettc@chw.edu.au
Ph: (02) 9845 1204
Website: www.chw.edu.au/research/groups/oncology/

For specific project-related enquiries, please contact the supervisor listed.

Outline of projects available

Molecular diagnosis of childhood malignancy using microarray technology

Supervisor/Research Group Leader: Dan Catchpoole PhD
Research Group: Tumour Bank and Molecular Diagnostics, Oncology Research Unit
Project: Honours Project
Email: danielc@chw.edu.au
Ph: (02) 9845 1205

Cancer is the second highest killer of children in Australia. Acute lymphoblastic leukaemia (ALL) is the most common type of childhood cancer (0-14 years). Despite the great advances that have been made with the health, well-being and welfare of children with ALL, such that close to 80% of paediatric ALL cases eventually survive, dealing with the recurrence of the disease or 'relapse' remains the major obstacle for the clinical management of this malignancy. Patients in designated 'high risk' categories, based on clinically and laboratory defined prognostic markers, have a very poor likelihood of cure. With the advent of 'microarray' technology, it is now feasible to analyse greater than 10000 genes in one experiment, creating a gene expression profile for the particular tumour sample. This will allow for the specific classification of cancer, including ALL, which is essential in guiding treatment. There is a vital need to reliably identify ALL patients at greater risk of relapse, who can then undergo modified therapy prior to recurrence of disease. We hypothesise that the profile of gene expression at the diagnosis of ALL in children, as determined through cDNA microarray analysis, will predict clinical response of patients to current therapeutic regimens and specifically, their likelihood of relapse and overall survival. This project will require you to determine the gene expression profiles in bone marrow specimens taken at diagnosis which are predictive for the response of ALL patients to current treatment protocol.

Examination of the association of morphological, molecular and genetic prognostic indicators in different cell types within neuroblastoma tumours

Supervisor/Research Group Leader: Dan Catchpoole PhD
Research Group: Tumour Bank and Molecular Diagnostics, Oncology Research Unit
Project: Honours/Masters Project
Email: danielc@chw.edu.au
Ph: (02) 9845 1205

Neuroblastoma, the most common solid tumour that affects infants, comes in various grades, each requiring different clinical management. In order to select the best treatment for a particular individual, it is essential that an accurate description be made of the malignancy by pathologists. Assessment of molecular and genetic differences between individual tumours has assisted with predicting how aggressive the disease will be. Little is known however, about how these molecular and genetic changes may influence tumour growth and development. Furthermore, neuroblastoma tumour masses consist of a mixture of different cell types, but which ones are actually affected by these molecular and genetic factors has yet to be determined. We propose to solve this problem by isolating specific populations of the cell types from neuroblastoma tumours stored with the Tumour Bank using a novel laser-assisted microscopic procedure. 'Laser capture microdissection' has been developed to isolate pure populations of cells from specific microscopic regions of tissue sections. Once collected, these isolated cells will undergo analyses for molecular and genetic changes, specifically using reverse transcription PCR and microarray technology, which will pin point the crucial malignant cells within a tumour which should be made the target for future new treatments.

Adhesion signalling as a potential treatment target in the childhood cancer neuroblastoma

Supervisor/Research Group Leader: Geraldine O'Neill, PhD
Research Group: Focal Adhesion Biology in Cancer, Oncology Research Unit
Project: Honours/PhD Projects
Email: geraldio@chw.edu.au
Ph: (02) 9845 3116

The childhood cancer neuroblastoma is a disease that occurs in young babies. Among children diagnosed with a high-risk category of the disease there is currently only a 40% survival rate after treatment. Therefore there is an urgent need to try and improve current treatment success rates. In laboratory-based models of neuroblastoma 3 distinct groups of neuroblastoma are seen. These groups are distinguishable by their cell shape and adhesion characteristics, with the most aggressive form being the least adherent. Our laboratory studies the changes in cell adhesion that are observed in cancer cells and how these changes effect both the progression of the cancer and the response of the cancers to treatment. We use a variety of molecular and cellular biology techniques in our studies. Available Honours projects include the study of the adhesion of the 3 different classes of neuroblastoma to determine the adhesion signalling pathways in these cells. By dissecting adhesion signalling in these cells we aim to identify potential new targets for therapies for improved neuroblastoma treatments.

How D52-like proteins function in normal and cancer cells

Supervisor/Research Group Leader: Jennifer Byrne PhD
Research Group: Molecular Oncology Group, Oncology Research Unit
Project: Honours/PhD Projects
Email: jennifeb@chw.edu.au
Ph: (02) 9845 3027

Our group is focussing upon determining the functions of a novel group of genes, the D52 (or TPD52) family, which we have identified as being expressed in human breast cancer. We have found that D52 represents a target for gene amplification in breast cancer, and is likely to therefore play a causal role in the development of this disease. Very little is known of the functions of D52 and related proteins in cells, a situation which must be reversed in order to understand how D52-like over-expression may advantage tumour cells, and how targeting D52-like proteins may improve cancer diagnosis or treatment. We have recently identified a new protein partner for D52-like proteins, which is a novel member of the MAL proteolipid family named MAL2. Current laboratory interests include analysing functional differences between D52-like proteins, the significance of interactions between D52-like proteins and MAL2 and other novel partners, the consequences of D52-like protein over-expression in model systems, and the endogenous expression of D52-like proteins in different forms of human cancer. Student projects are available in all of these areas.

Molecular genetics of cell and tissue structure

Supervisor/Research Group Leader: Prof. Peter Gunning PhD
Research Group: Cellular Oncology Group, Oncology Research Unit
Project: Honours/PhD Projects
Co-Supervisors: Galina Schevzov PhD, Bernadette Vrhovski PhD
Email: galinas@chw.edu.au or bernadev@chw.edu.au
Ph: (02) 9845 3116 or 9854 3115

The lab has a long-standing interest in the role of the actin cytoskeleton in both the generation and regulation of cell shape. All cells have a characteristic shape that is intrinsic to cellular function. Inappropriate alterations in cell shape is characteristic of cancer cells and we suspect that these changes play a direct role in cancer pathology. Actin and tropomyosin isoforms are the major building blocks that contribute to the structure of cells. The use of actin and tropomyosin isoform specific antibodies has allowed us to identify spatially and temporally regulated intracellular compartments. The finding that different isoforms can be targeted to different sites within cells suggests that they have different functional roles. In order to dissect the function of these structural isoforms we are currently employing gene knock out and transgenic mice technology. We are currently analysing the impact that these genetically manipulated mice may have on cell and tissue anatomy. Students projects will include the analysis of genetically manipulated embryonic stem cells and/or cell lines to determine the impact that altered tropomyosin gene expression may have on cell morphology/differentiation and expression/subcellular localisation of cytoskeletal signalling molecules.

Mighty Mouse: Expression and function of a DNA repair enzyme in a transgenic mouse

Supervisor/Research Group Leaders: Prof. Peter Gunning PhD, Dr Geoff McCowage
Research Group: Cellular Oncology Group and Cancer Gene Therapy Initiative, Oncology Research Unit
Project: Honours Project
Contact: Belinda Kramer
Email: geoffm@chw.edu.au or belindak@chw.edu.au
Ph: (02) 9845 3115 (Belinda)

Chemotherapy drugs would effectively kill all of the tumour cells in a patient if they could be given at high enough doses. It is the toxic side effects that these drugs have on normal cells, such as bone marrow stem cells, that become dose limiting in cancer treatment. The focus of our research has been on developing a gene therapy approach to reduce the toxicity of chemotherapy drugs by providing chemoprotection to bone marrow stem cells. More recently we have been working on producing a transgenic mouse line which expresses a human DNA repair enzyme that protects cells from the effects of chemotherapy drugs. Although our current work aims to use this transgenic mouse in developing bone marrow transplant models, this mouse line provides an opportunity to develop therapies for a wide variety of disease models. An honours project would involve investigation of transgene expression levels in different mouse tissues and functional analysis of transgene expression. Functional analysis would involve the development of novel in vitro assays (tissue culture) to assess drug resistance in different cell populations derived from the mice. A student could gain experience in techniques such as western blotting, PCR, flow cytometry and tissue culture.

Muscle stem cell therapy

Supervisor/Research Group Leaders: Prof. Peter Gunning PhD, Edna Hardeman
Research Groups: Oncology Research Unit, The Children's Hospital at Westmead and Muscle Development Unit, Children's Medical Research Institute
Project: PhD Project
Contact: Prof. Peter Gunning on (02) 9845 3045, e-mail: peterg3@chw.edu.au
Dr. Edna Hardeman on (02) 9687 2800, e-mail: ehardeman@cmri.usyd.edu.au

Muscle stem cells that can give rise to muscle cells or fibres reside in various adult tissues. These include skeletal muscle, bone marrow and the aorta. Skeletal muscle has the ability to repair itself when damaged because of the presence of stem cells that reside in the muscle beds. Dystrophies are diseases of muscle in which the muscle is chronically damaged and undergoing repair. Muscle stem cells from the different sites within the body are currently being tested to determine which can be genetically modified in cell culture and then introduced into the dystrophic muscle to correct genetic defects and halt chronic muscle damage. We have devised a method of giving the genetically corrected muscle stem cells a selective survival advantage in dystrophic muscle. This project will determine the efficiency of this stem cell therapy approach. This project will be carried out in collaboration with members of the National Stem Cell Centre. Model systems include stem cell culture, transgenic mice and mouse models of muscular dystrophy. Techniques cover cell sorting, immunohistochemistry, individual rodent muscle strength measurements, testing of muscle physiological parameters in vitro and in vivo, immunohistochemistry, Western blotting and confocal and electron microscopy.