Student Opportunities 2002

Herpes Virus Research Unit

Head: Cheryl Jones MBBS PhD
Email: CherylJ@chw.edu.au

Projects are available for (yes/no):
Vacation scholars: No
Honours students: Yes
PhD students:Yes

Outline of projects available for 2002

• Factors that determine the induction of a protective T cell response to herpes simplex virus in neonatal mice.
• The role of antigen presenting cells in the neonatal murine immune response to herpes simplex virus infections.
• The effect of HSV infection on the murine dendritic cell cytoskeleton

Molecular Oncology Laboratory, Oncology Research Unit

Head: Jennifer Byrne PhD
Email: JennifeB@chw.edu.au

Projects are available for (yes/no):
Vacation scholars: Yes
Honours students: Yes
PhD students: Yes

Outline of projects available for 2002

How D52-like proteins function in normal and cancer cells
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 analyzing 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.

Research Group/Unit: Tumour Bank, Oncology Research Unit

Head: Dan Catchpool PhD
Email: DanielC@chw.edu.au

Projects are available for (yes/no):
Vacation scholars: Yes
Honours students: Yes
PhD students: Yes

Outline of projects available for 2002

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

Cellular Oncology and Neuro-Oncology Laboratories, Oncology Research Unit

Head: Peter Gunning PhD (Cellular Oncology)
Email: PeterG3@chw.edu.au

Head: Ron Weinberger PhD (Neuro-Oncology)
Email: RonW@chw.edu.au

Projects are available for (yes/no):
Vacation scholars: Yes
Honours students: Yes
PhD students: Yes

Outline of projects available for 2002

Both groups are involved in determining how the actin cytoskeleton contributes to cell structure and development as well as exploring the role of this system in cancer and other diseases. In cancer in particular, abnormalities in the actin cytoskeleton are one of the earliest changes identifiable and it is thought that by preventing these structural changes it may be possible to prevent the progression of the disease. One way in which the actin based cytoskeleton can cause changes is by using different isoforms in the development of cell structures. In disease one or more of these isoforms is either mistargetted, down regulated or absent. The isoforms that the laboratories have studied are the actin and tropomyosin families. It is thought that at least one of the tropomyosins can function to suppress tumour growth and these families may be future drug targets. Current interests of the labs and potential honours projects include:

• Looking at the sorting of tropomyosins using fluorescently labelled isoforms that can be transfected into live cells and visualised in real time using confocal microscopy (visually stunning!).
• Tumour suppressor capabilities of tropomyosin isoforms (potential cancer targets?).
• The role of tropomyosins in neuronal growth and development using transgenic animals (learn how to make beautiful primary neurons in culture!)
• Signalling mechanisms leading to cytoskeletal rearrangement and how the composition of the cytoskeleton can impact on how signal are interpreted. This includes understanding the role of progesterone receptors in breast cancer development.

Cancer cell interactions with the external environment: implications for tumour development and therapy.
Contact: Geraldine O'Neill, PhD (NHMRC Howard Florey Research Fellow)
Email: GeraldiO@chw.edu.au

Cells are anchored in our bodies through the formation of focal adhesion sites. Not only do focal adhesions provide structural support and therefore contribute to cell shape, they additionally transmit signals from the external environment that tell the cell to undergo a number of different processes including moving, dividing and dieing. A cancer cell characteristically divides more than non-cancerous cells and is resistant to death, while it is the relocation (moving) of cancer cells to a secondary site (metastasis) that causes a cancer to be fatal. These 3 processes are therefore fundamental to the development of cancer and so my research is focused on the regulation of focal adhesions. Included among current projects are:

• What is the contribution of focal adhesion signals to chemotherapy? That is, can focal adhesion signalling protect cancer cells against chemotherapy and therefore contribute to drug resistance, a major obstacle in cancer treatment?
• Examine the role of post-translational processing of focal adhesion components in signalling through focal adhesions. How do these different post-translational events effect signalling through the focal adhesions?
• Search for target molecules that are cleaved by proteases during the cell rounding that accompanies cell division. So far only one molecule is known to be targeted this way (a protein that I worked on during a 3 year post-doctoral position in the US) - identification of further targets will support a new theory of protein signalling during mitosis.