Associate Professor Andrew Collins
- 2002-present: Associate Professor, School of BABS
- 2008-2010: Deputy Head of School, School of BABS
- 2000-2002: Head of School, UNSW School of Microbiology & Immunology
- 1991-2002: Lecturer; Senior Lecturer, UNSW School of Microbiology & Immunology
- 1990: Research Scientist, Division of Pathology, Royal Children's Hospital, Melbourne
- 1985-1986: Research Assistant, WHO Collaborating Centre for the Epidemiology of Diabetes Mellitus, Southern Memorial Hospital, Melbourne
- 1981-1984: Assistant to Director, Papua New Guinea Institute of Medical Research, Goroka
My group focuses upon the analysis of immunoglobulin gene sequences. We have a longstanding interest in the analysis of IgE-associated VDJ genes, and more recently have focused upon IgG-associated VDJ genes.
There are four human IgG subclasses, and curiously, the two most prominent IgG subclasses (IgG1 and IgG2) have essentially opposing functions. IgG1 fixes complement and binds to the low affinity Fc gamma RII and Fc gamma RIII, while IgG2 neither fixes complement nor binds effectively to these Fc gamma Rs. Yet, despite these opposing functions, both subclasses are often produced in response to antigen exposure.
We recently proposed the Temporal Model of human IgE and IgG antibody function to address this paradox (http://dx.doi.org/10.3389/fimmu.2013.00235). The Temporal Model suggests that there is a dominant pathway of sequential switching between the IgG subclasses. The model does not deny the possibility of additional switch pathways. Nor does it assume that all immune responses involve switching at equal speed along the pathway, as this might, for example, be moderated by the action of cytokines. And antigen clearance may terminate a response when cells are at any point along the pathway, leading to the dominance of different IgG subclasses according to the duration of an antigenic threat.
Nevertheless, a dominant pathway can be described which reflects the chromosomal order of the IGHG genes within the constant region gene locus. This ensures that each isotype has broadly predictable affinity for antigen, relative to other isotypes, and it is the relative affinities between isotypes, as well as the variable half-lives and other physico-chemical properties of the subclasses, which allow a complex multi-subclass IgG response to deliver effective protective immunity.
In addition to our studies of immunoglobulin isotypes, my group continues to study the processes that give rise to the diversity of the immunoglobulin gene repertoire, and to biases and constraints that shape the immunoglobulin gene repertoire. We recently proposed that the immunoglobulin gene repertoire has ‘shape’ because the probabilities that different VDJ gene rearrangements will be generated vary by many orders of magnitude (http://dx.doi.org/10.3389/fimmu.2013.00263).
A relatively small number of unique rearrangements are generated with probabilities high enough to ensure that they are carried by a large number of B cells, in any individual. In contrast, an individual may have only a single B cell that carries a rearrangement of lower probability, or it may be entirely absent from their repertoire. This ‘shape’ must undoubtedly have profound consequences for the way the immune system operates, and the exploration of repertoire shape is now a major focus of our group.
A final important contribution of our group to immunoglobulin gene research continues to be our evaluation of both the completeness and the accuracy of the reported germline gene repertoires. We have identified almost 100 reported immunoglobulin alleles that have been reported in error, and which should be removed from the germline sequence databases (http://dx.doi.org/10.1038/sj.icb.7100144). We have also identified 21 new allelic variants, and have inferred the existence of a further 22 putative polymorphisms, using bioinformatic analysis.
The resulting UNSWIg IGHV germline gene repertoire is available at http://www.ihmmune.unsw.edu.au/UNSWIgVRepertoire.fasta.
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: Journal of Immunology, Immunology, Int. Archives of Allergy & Immunology, BMC Immunology, BMC Bioinformatics etc