We have developed new strategies for the accurate identification of the genetic elements that together make up immunoglobulin genes. This strategy allowed us to develop large databases of partitioned sequences, from which we could quantify the contributions that different processes make to the generation of diversity. In turn, this led to the development of a hidden Markov Model-based approach to the partitioning of...view more
We have developed new strategies for the accurate identification of the genetic elements that together make up immunoglobulin genes. This strategy allowed us to develop large databases of partitioned sequences, from which we could quantify the contributions that different processes make to the generation of diversity. In turn, this led to the development of a hidden Markov Model-based approach to the partitioning of immunoglobulin genes. Our alignment utility has been objectively demonstrated to be the most accurate tool available.
Using our alignment utility, we have compiled very large databases of partitioned heavy and light chain genes, allowing us to evaluate both the completeness and the accuracy of the reported gene repertoires. We have been able to identify over 100 reported immunoglobulin genes that have been reported in error, and which should be removed from the germline sequence databases. We have identified many new IGHV gene poymorphisms, mostly in individuals from Papua New Guinea, though these genes have since been found in individuals from many parts of the world. We have also identified manynew putative polymorphisms, using our bioinformatic analysis, and have gone on to confirm the existence of 5 of these putative polymorphisms by genome screening.
The development of our improved alignment utility, and our understanding of the repertoire of available germline genes, has meant that in recent years we have established a number of collaborations to analyse sequences generated in high-throughput sequencing projects. This has led to teh development of techniques for the inference of genotypes - the complete set of germline IGHV, IGHD and IGHJ genes that are found in an individual's genome. Our analysis has revealed substantial differences between the genotypes of diffeent individuals, with evidenc of substntial numbers of deletion polymorphisms as well as gene duplications. Together, these data suggest substantial differences may exist between individuals, with respect to their ability to generate diverse antibody repertoires.
- 1981-1984 Assistant to the Director, Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea
- 1985-1986 Research Assistant, WHO Collaborating Centre for the Epidemiology of Diabetes Mellitus, Southern Memorial Hospital, Melbourne
- 1990 Research Scientist, Division of Pathology, Royal Children's Hospital, Melbourne
- 1991-2002 Lecturer, Senior Lecturer, UNSW
- 2002-present Associate Professor, UNSW
Honours & Awards
- Vice-Chancellor's Award for Teaching Excellence 1999
- UNSW Nominee, Australian University Teaching Award 1999
- Grant Reviewer (NHMRC, ARC, NZ Health Reseach Council)
- Reviewer for journals including: PNAS, Nature Genetics, Nucleic Acids Research, Journal of Immunology, Immunology, Immunology and Cell Biology, BMC Immunology, BMC Bioinformatics and others.
Mast cells & the allergic response; Hepatic mast cells & gastrointestinal hypersensitivity