Current Research Projects
- Sex Determination in Monotremes
Sex determination is one of the most puzzling aspects of monotreme biology. They have an extraordinary complex sex chromosomes system that consists of ten sex chromosomes in platypus and nine in echidna. In contrast to sex chromosomes in other mammals, platypus sex chromosomes show extensive homology to bird sex chromosomes.
In addition the mammalian sex determining gene SRY is missing in platypus. We are investigating candidate sex determining genes (know mammalian sex determination genes) and we are identifying and characterising new genes on the Y specific parts of the five Y chromosomes in platypus to get insight into how sex is determined in these animals. This will also potentially identify new sex determination and spermatogenesis genes in other mammals including humans.
- Meiotic Sex Chromosome Inactivation
Monotremes present a unique biological challenge in the context of MSCI formation as their sex chromosome complement far exceeds that of most therians due to their remarkable 10 sex chromosomes (platypus). A significantly greater amount of unpaired DNA is therefore present in spermatocytes at meiosis and an increased number of genes are potentially impacted by any enforced silencing. This project aims to establish whether the platypus and echidna sex chromosome DNA undergoes equivalent epigenetic modifications and gene silencing to that observed in mouse.
During spermatogenesis in mammals, the X and Y sex chromosomes undergo a complex series of epigenetic modifications to effect genetic silencing, termed meiotic sex chromosome inactivation (MSCI). Accompanying these changes is the event of ‘sex body’ formation at male meiotic prophase I, a process in which the sex chromosomes undergo chromatin condensation and are clearly visible at the nuclear periphery, separate from the synapsed autosomes.
- X Inactivation in Monotremes
In mammals a sex chromosome system has evolved where males have one X chromosome and a very gene poor Y chromosome and females have two copies of the X chromosome. This means females have two copies of many X-linked genes while males have only one copy. In order to compensate for the difference in gene dosage in females one X chromosome is inactivated in all somatic cells. This inactivation is initiated through expression of the Xist gene from the inactive X. In addition, epigenetic modifications such as DNA methylation, histone deacetylation and histone variants like macroH2A play an important role in the transcriptional silencing of one of the X chromosomes.
It has recently been shown that the Xist gene has evolved only recently in the eutherian lineage. So far nothing is known about dosage compensation and X inactivation in monotremes but it is particularly interesting to investigate this in monotremes as they feature five pairs of X chromosomes in females and in males one copy of each of these X chromosomes and five Y chromosomes in platypus and four Y chromosomes in echidna. We investigate if X inactivation occurs by combination of immunostaining with antibodies and fluorescence in situ hybridisation with X-specific DNA probes on fibroblast cell lines and western blotting to detect epigenetic changes on the X chromosomes in females. This will reveal whether or not dosage compensation and X inactivation occurs in female monotremes.
- Reproductive Biology of Free Ranging Echidnas
Echidna trains can be observed during breeding season where several mature males follow one female. Which of the males is mating successfully? This is one of the questions we address by using a combination of radio tracking and molecular genetics on echidnas at Monarto Zoo. In this project we also investigate other general aspects of echidna ecology, population genetics and development.
- Inflammatory Pathway in Platypus
The inflammatory response pathway in humans involves four caspases, caspase-1, -4, -5 and caspase-12. Caspase-1 is activated in response to many bacterial pathogens through inflammasome formation, similar to apoptosome assembly, which leads to caspase-9 activation. Active caspase-1 targets and cleaves the proinflammatory cytokines IL-1 and IL-18 leading to their secretion by the cell to produce an inflammatory response. Specific bacterial or fungal pathogens can initiate distinct inflammatory responses in regard to the mode of caspase-1 activation and a major question is how response specificity is determined.
To date we have no information about the molecular mechanism underlying the inflammatory response in platypus. This project aims to characterise the dynamics of the inflammatory response in a monotreme cell culture system established in our laboratory. In addition to unravelling a basic biological pathway in platypus we will use this to investigate the inflammatory response to a potentially lethal fungal infection that effects platypus in Tasmania.
- Epigenetics of Bovine Hybrids
In inter- and intra-specific hybrids different genomes are combined and forced to interact. We hypothesise that novel genetic and epigenetic interactions in hybrid genomes cause major differences in gene regulation and gene expression. In collaboration with Prof. S. Hiendleder we use hybrid embryos of the commonly bred Angus (Bos p. taurus) and Brahman (Bos p. indicus) cattle to study the genetic and epigenetic basis of hybrid phenotypes.