f.foong@unsw.edu.au

Development of human gene therapies.

The application of molecular biology, cell biology and chimeric protein production techniques to investigate challenging problems in the search for new biopharmaceuticals and treatment.

Program 1: Detection of novel human gene regulatory regions and their genes

With advances in human genome sequencing, it is imperative to detect promoter and regulatory regions and their genes, and characterize their functions for use in studies of human disease and possible therapies. The cloning of functional regulatory regions and their genes is therefore essential. Their expression profiles can also be studied to reveal information regarding metabolic pathways, gene function as well as mechanisms of toxicity of compounds.

Mammalian promoters and regulatory regions are also very useful in the regulated expression of recombinant proteins. The number of human gene promoters and regulatory regions described in the literature are relatively few due to the lack of an efficient way to detect these sequences in mammalian cells.

This project aims to develop a novel and sensitive visual method to screen, detect and clone these sequences. Regulatory regions which are detected will then be characterized. The novel vector systems for screening and detection of these sequences have been constructed and are being modified and tested for their efficiency and functionality. Aspects of the project will therefore involve recombinant DNA work, cell biology, FACS (fluorescent activated cell sorting), fluorescent microplate quantification and microscopy techniques. We have collaborations with Phase-1 Molecular Toxicology, Inc. Santa Fe, New Mexico, USA. This company utilises DNA gene microarrays and high-throughput assays to generate data regarding a compound's mechanism of toxicity and to screen for biologically active compounds for potential use as biopharmaceuticals. They also have a bioinformatics department for analysis and processing of the data. 

Program 2: Development of chimeric proteins for targeted gene delivery

This is an ARC-SPIRT project in collaboration with Dr. Robert Nordon, Graduate School of Biomedical Engineering and commercial partner FH Faulding & Co. Ltd., Adelaide. The objective of this research project is to develop chimeric proteins for the targeted delivery of DNA into haematopoietic and immune system cells. Potential targets include genetic and acquired blood disorders which do not yet have conventional treatment such as thalassaemia, severe combined immunodeficiency, haemophilia, HIV and leukemia.

Our initial research will focus on using characterised functional domains from various proteins which can increase the efficiency of DNA delivery into cells by using one or a combination of the following methods i) targeting and binding to cell receptors ii) endosomal escape to avoid degradation iii) nuclear targeting and localisation.

Aspects of the project will involve chimeric protein production by recombinant DNA techniques, and characterisation and assessment of the functional domains in targeted gene delivery with cell biology techniques, laser and cell cytometry, confocal microscopy and fluorescent microplate reader quantification.