We study comparisons of the genomes of distantly
related mammals and other vertebrates. We specialise in
Australian mammals.
Marsupials
(e.g. kangaroos, wallabies) and monotremes (e.g. platypus) are
the mammals most distantly related to humans, so we can use comparisons
of their DNA sequences and gene arrangements.
To explore the organisation, function and evolution of the human
genome. We are particularly interested in how sex (maleness or
femaleness) is determined in mammals. We are also comparing
genomes of birds and reptiles with those of mammals.
We are also using a comparative strategy to explore the mechanism
and evolution of complex gene regulatory circuits like X chromosome
inactivation and genomic imprinting. We aim to determine how these
systems work and also why they evolved.
Current Research
Genome organisation and evolution
We use "chromosome painting" to see how chromosomes
have changed during evolution. The same genome regions are arranged
and rearranged in chromosomes like pieces of a jigsaw puzzle.
We study how chromosomes are organised in the nucleus of somatic
cells and sperm and apply this to suggest how position affects
activity.
Kangaroo Genomics
With the formation of the ARC Centre for Kangaroo Genomics (KanGO), we
will be characterising the X chromosome and an autosome by genetic
and physical mapping, then ordering and contigging BAC clones
along their length. Ultimately, we hope to completely sequence
this part of the genome.
Sex determination and spermatogenesis
Mammals determine sex by means of the SRY gene on the
Y chromosome, which triggers testis differentiation. We are investigating
how this gene evolved from an original brain determining gene
on the X chromosome. We are also studying other genes in the sex
determining pathway, as well as genes on the Y chromosome required
for male fertility. We are looking at sex determination
in reptiles, particularly those that indulge in both temperature
and genetic sex determination.
Sex chromosome evolution
The Y chromosome is interesting because it contains few genes
and lots of junk DNA. We are studying homologues of human Y chromosome
genes to investigate how some genes can acquire new functions
while others are degraded and lost during evolution. The X chromosome
is also unusual because it is present in one copy in males and
two in females and seems to have a high concentration of genes
involved in sex and reproduction, as well as intelligence genes.
Sex chromosomes of birds and snakes are quite different in gene
content, but have many parallels.
Epigenetic control of gene activity
The X chromosome is present in one copy in XY males and two in
XX females, but one copy is inactivated in females. We are investigating
how the locus XIST controls the process of transcriptional
repression. In particular we are studying the evolution and function
of XIST in kangaroos, where X inactivation is partial and
only affects the father's X chromosome, and discovering the mode
of dosage compensation in the platypus.
