Head

Associate Professor Greg Goodall

Address	Department of Human Immunology Institute of Medical & Veterinary Science Frome Road, Adelaide, South Australia, 5000
Phone	+61 8 8222 3430
Fax	+61 8 8232 4092
Email	Greg.Goodall@imvs.sa.gov.au
	Research Interests

Affiliations: Associate Professor , Discipline of Medicine, University of Adelaide

Qualifications: B.Sc. (Adelaide), PhD (Adelaide)

Experience:

Lab Members

Back row (L to R): Philip Gregory, Andrew Bert, Dominik Kaczorowski
Front row: Emily Paterson, Greg Goodall

Research Interests

Cytokines regulate the immune system, but can also play a role in cancer. We aim to understand how the production of cytokines is regulated through the control of messenger RNA degradation. Growth factors, also known as cytokines, regulate the growth and activities of many cells, including the cells of the immune system. Thus it is important for good health that the production of the growth factors is properly controlled. One way in which growth factor production is controlled is by regulating the degradation and replacement of the messenger RNA molecules that specify the details of growth factor synthesis. We are studying how the rate of degradation of these messenger RNA molecules is controlled. This is important not only for understanding how cytokine production is regulated in normal cells during immune and inflammatory responses, but also has implications in cancer. The overproduction of growth factors due to abnormal stability of the mRNA has been observed in various types of cancer cell and is believed to contribute to tumour growth.

MicroRNAs perform critical functions in regulating gene expression during development, and during cancer growth. MicroRNAs are a recently discovered class of small RNA molecules that control gene expression in plants and animals. In the past 5 years, these molecules have been shown to be critical regulators of several developmental pathways and can be informative diagnostic indicators of cancer progression. There are over 500 microRNAs in humans, but for most the functions and gene targets are unknown. We use microRNA microarrays to identify microRNAs whose expression changes when cells undergo developmental changes, especially those related to cancer development and progression, and use various techniques to identify targets and functions of the microRNAs.

Back to top

Selected Recent Publications

• Gregory,P.A. Bert,A.G. Paterson,E.L. Barry,S.C. Tsykin,A. Farshid,G. Vadas,M.A. Khew-Goodall,Y. Goodall,G.J. The microRNA-200 family and miR-205 regulate epithelial-mesenchymal transition by targeting the E-cadherin repressors, ZEB1 and SIP1. Nature Cell Biol.  Acccepted 13 Feb 2008
  
  
• R. A. Putland, T. A. Sassinis, J. S. Harvey, P. Diamond, L. S. Coles, C. Y. Brown and G. J. Goodall: RNA destabilisation by the G-CSF Stem-Loop Destabilising Element involves a single stem-loop that promotes deadenylation. Mol. Cell Biol. 22 (6); 1664-1673, 2002.
  
  
• K. J. D. Lang, A. Kappel and G. J. Goodall: Hypoxia Inducible Factor-1? mRNA Contains an Internal Ribosome Entry Site that allows efficient translation during hypoxia. Mol. Biol. Cell 13;1792-1801, 2002.
  
  
• L.S. Coles, P. Diamond, L. Lambrusco, J. Hunter, J. Burrows, M.A. Vadas and G.J. Goodall: A novel mechanism of repression of the VEGF promoter by single strand DNA binding cold shock domain proteins (Y-box) in normoxic fibroblasts. Nucl. Acids Res 30: 4845-4854, 2002.
  
  
• G.J. Goodall, L.S. Coles, M.A. Bartley and K. J. D. Lang: Post-transcriptional regulation of VEGF. In “Genetics of Angiogenesis”, J. Hoying ed. BIOS Scientific Publishers Ltd. Oxford UK, 69- 83, 2003.
  
  
• R. T. Sladic, C. A. Lagnado, C. J. Bagley and G. J. Goodall: Human PABP Binds AU-rich RNA via RNA-Binding Domains 3 and 4. Eur. J Biochem. 271: 450-457, 2004.
  
  
• L.S. Coles, M.A. Bartley, A.G. Bert, J. Hunter, S.W. Polyak, P. Diamond, M.A. Vadas and G.J. Goodall: A multi-protein complex containing cold shock domain (Y-Box) and polypyrimidine tract binding proteins forms on the vascular endothelial growth factor mRNA - potential role in mRNA stabilization. Eur. J. Biochem 271: 648-660, 2004.
  
  
• Z.-J. Su, C. N. Hahn, G. J. Goodall, N. M. Reck, A. F. Leske, A. Davy, G. Kremmidiotis, M.A. Vadas and J.R. Gamble. A Vascular Cell Restricted RhoGAP, p73RhoGAP, is a Key Regulator of Angiogenesis. Proc. Natl. Acad. Sci. USA, 101; 12212-12218, 2004.
  
  
• J. Zhou, M Callapina, G. J. Goodall, and B. Brüne. Functional Integrity of Nuclear Factor kB, Phosphatidylinositol 3’-Kinase, and Mitogen-Activated Protein Kinase Signaling Allows Tumor Necrosis Factor a-Evoked Bcl-2 Expression to Provoke Internal Ribosome Entry Site-Dependent Translation of Hypoxia-Inducible Factor 1a. Cancer Res.64; 9041-9048, 2004.
  
  
• C.N. Hahn, Z.J. Su, C.J. Drogemuller, A. Tsykin, S.R. Waterman, P.J. Brautigan, S. Yu, G. Kremmidiotis, A. Gardner, P.J. Solomon, G.J. Goodall, M.A. Vadas and J.R. Gamble. Identification Of Functionally Important Genes And Co-Ordinately Regulated Signalling Pathway Genes In Angiogenesis In Vitro. Physiol. Genomics, 22; 57-69, 2005
  
  
• A.L. Brown, C.R. Wilkinson, S.R. Waterman, C.H. Kok, D.G. Salerno, S.M. Diakiw, B. Reynolds, H.S. Scott, A. Tsykin, G.F. Glonek, G.J. Goodall, P.J. Solomon, T.J. Gonda and R.J. D’Andrea. Genetic regulators of myelopoiesis and leukemic signalling identified by gene profiling and linear modelling. J. Leukocyte Biol. 80: 433-47, 2006
  
  
• Bert AG, Grepin R, Vadas MA, Goodall GJ. Assessing IRES activity in the HIF-1a and other cellular 5' UTRs. RNA 12; 1074-1083, 2006.

See a PubMed listing of Dr Greg Goodall's publications

Back to top

Funding

Available Student Projects

Broad area of research
For many key regulatory proteins, whose levels can change rapidly in response to physiological events, the control of translation and turnover of mRNA play crucial roles in regulating expression of the encoded proteins. MicroRNAs perform critical functions in regulating gene expression during development, and during cancer growth. We use molecular and cell biology techniques, such as gene manipulation, reporter genes, microarrays and real time PCR to study the underlying molecular mechanisms of regulation.

Research projects offered in 2007

1. MicroRNAs in tumour metastasis
Tumour metastasis, the major cause of death from breast cancer, involves the dissociation and migration of cells away from the primary tumour. To achieve this, the tumour cells recapitulate a process that normally occurs in early development, in which epithelial cells that are normally tightly associated with their neighbouring cells, acquire the features of mesenchymal cells, which can migrate. This epithelial-mesenchymal transition (EMT) requires a molecular reprogramming of the cell, involving the downregulation of numerous epithelial genes and the induction of numerous mesenchymal genes (1). MicroRNAs are a recently discovered class of small RNA molecules that control gene expression in plants and animals. In the past 5 years, these molecules have been shown to be critical regulators of several developmental pathways (2) and informative diagnostic indicators of cancer progression (3). There are over 500 microRNAs in humans, but for most the functions and gene targets are unknown. We have used a microRNA microarray, to identify microRNAs whose expression changes when epithelial cells undergo EMT. This project involves examining the role of these regulated microRNAs in tumour metastasis and identifying the pathways through which they operate. The findings of this work may be used as a basis for microRNA-based approaches to blocking metastasis.

Collaborator: Dr. Yeesim Khew-Goodall, Hanson Institute, IMVS

Relevant publications

(1) Huber MA et al (2005) Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol17(5):548-58.

(2) Plasterk, RH (2006) MicroRNAs in Animal Development. Cell 124(5), 877-881

(3) Lu J et al (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043): 834-38.

**************

2. Multiple stability-regulating elements in the IL-2 mRNA
Interleukin-2 is a major T cell mitogen and driver of immune responses. Consequently, the IL-2 mRNA is highly regulated, being very rapidly turned over in quiescent T cells, but is stabilised when T cells become activated. This stabilisation contributes to a hundred-fold increase in IL-2 production in stimulated cells responding to an infection. When the infection subsides, the IL-2 mRNA is rapidly degraded, ensuring the shut-off of production of the potent cytokine. The IL-2 mRNA is therefore an excellent model for regulated mRNA turnover (4). We have discovered a novel instability element in the IL-2 mRNA that is likely to regulate its half-life (5,6). The aim of this project is to understand how the element is required for response to this signalling pathway, and to identify the other gene products involved, and the molecular mechanism that causes this response.

Collaborator: Dr. Enrico Gherzi, National Cancer Research Institute, Italy

Relevant publications:

(4) Chen CY, Gherzi R, Andersen JS, Gaietta G, Jurchott K, Royer HD, Mann M, and Karin M. (2000) Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation. Genes Dev. 14:1236-1248.

(5) C.Y. Brown, C.A. Lagnado, and G.J. Goodall: A cytokine mRNA-destabilizing element that is structurally and functionally distinct from A+U-rich elements. Proc. Natl. Acad. Sci. USA 93: 13721-13725, 1996.

(6) R. A. Putland, T. A. Sassinis, J. S. Harvey, P. Diamond, L. S. Coles, C. Y. Brown and G. J. Goodall: RNA destabilisation by the G-CSF Stem-Loop Destabilising Element involves a single stem-loop that promotes deadenylation. Mol. Cell Biol. 22 (6); 1664-1673, 2002.

Back to top