Over the past 15 years, we have been interested in the genetics of the iconic platypus and echidna. We strive to use our discoveries to help species conservation, and to better understand our own genetic history and human diseases.
The comparison of genes, genomes and epigenetic mechanisms in different species has provided many fundamental insights into how genes function in humans, how they evolved, and how they contribute to diseases. Our group studies gene evolution in mammalian species distantly related to humans – monotremes in particular.
Monotremes have an extraordinary sex chromosome system that can reveal novel genes and pathways involved in sex determination and differentiation in all mammals, including humans. They also provide valuable insight into the beginnings of placentation and lactation in mammals. Monotremes have undergone radical changes to their stomach anatomy and physiology. Studying monotremes provides the opportunity to identify the role of key genes involved in stomach function and metabolism in humans, and may even lead to the identification of new therapeutic targets for metabolic diseases such as diabetes.
Identification and characterisation of monotreme sex determining genes
The generation of males and females in any animal population is crucial to success in species survival. Many different pathways of sex determination have evolved but certain genes/gene families have conserved functions in this process. The conserved mammalian sex determination gene, SRY is absent in egg-laying mammals (monotremes), the oldest living lineage of mammals. We are working to identify and characterise candidate sex determination genes in monotremes to shed light on the evolution of this process in mammals.
Monotremes have a unique sex chromosome system consisting of multiple XY sex chromosomes compared to the single XY sex chromosomes in other mammals. We are studying this unique system during meiosis in platypus spermatogenesis looking for sex-biased chromosome segregation.
Echidnas are an iconic Australian species and are the most widespread native mammal in Australia. However, there are still major knowledge gaps in terms of the distribution, biology and ecology of these fascinating animals. We have created a citizen science project, the Echidna Conservation Science Initiative – EchidnaCSI – using an innovative approach of combining public engagement with molecular biology to better understand wild echidna populations and to help their conservation. Through a specially designed app, the public take photos of echidnas in the wild to record their sightings for us to establish the first Australia-wide distribution map. The public also collect and send us echidna scats, allowing us to investigate the DNA and hormones within these scats. DNA helps us to understand the echidnas diet, population genetics and microbiome while hormones can show whether echidnas are stressed in particular environments and help us to better understand their reproduction. EchidnaCSI has now been running for over five years and we have more than 10000 users with 13000+ echidna sightings recorded and 800+ scats sent in from across Australia.
Evolution of the placenta and lactation in mammals
Physical mapping of the Echidna genome We are currently working in collaboration to sequence and map the echidna genome. Linda is contributing to this by the physical mapping of certain sequenced regions to echidna chromosomes using chromosomal Fluorescence in situ hybridization. A high resolution echidna genome sequence is an essential tool for molecular research and conservation of this iconic Australian mammal.
Echidna differential gene expression Monotremes, comprising solely of the platypus and echidna, are the oldest surviving mammalian lineage diverging from all other mammals approximately 200 million years ago. These animals have extraordinary reproductive and developmental biology being the only egg-laying mammals and seasonal breeders, yet much of the molecular mechanisms controlling these processes are unknown. For the first time, we have access to juvenile and out-of-breeding season adult echidna material that allows us to compare gene expression from brain and reproductive organs with matching in-breeding season adult material. From this material we are identifying interesting pathways that are differentially regulated between the tissues, which will allow us to better characterise monotreme reproduction and development.
Eunice's Project: The role of piRNA pathway genes in ovarian and prostate cancer A more recently discovered small non-coding RNA, piRNA, has caught the eye researchers worldwide as a potential cancer biomarker. Research to uncover the functions of this complex piRNA and its pathway genes (involved in piRNA biogenesis) is ongoing. Jumping on the bandwagon of cancer research, we aim to unveil the effects of piRNA pathway genes on key molecular characteristics and metastatic potential of cancer.
Ovarian cancer is the most lethal gynaecologic malignancy while prostate cancer ranks one of the most commonly diagnosed cancer in men. Together, they affect the lives of millions of people worldwide. While the effects of the piRNA pathway genes have been more broadly covered in many cancers, there are limited studies on their effects in ovarian and prostate cancer. Therefore, we would like to bridge this knowledge gap through my PhD project.
Natasha's Project: Metabolic genes of monotremes and diabetes Diabetes has become a major health burden, not only for Australia but worldwide. One of the major targets for treatment is the hormone glucagon-like peptide 1 (GLP-1), which helps the release of insulin to the blood stream and assists in glucose control. One problem with GLP-1 is that it is broken down within minutes of its release by and enzyme called DPP-4. In platypus and echidna this hormone has gained a mutation which has made it resistant to break down by DPP-4. This was recently shown in vivo along with the ability for platypus and echidna GLP-1 to assist with insulin secretion. The next steps in this project are to assess platypus and echidna GLP-1 in the mice model. We plan to inject 2 different mice models (insulin resistant and obese models) and analyse their glucose tolerance, weight, and other metabolic outcomes as a result of treatment. Alongside this, we will also be using a bioinformatics approach and access to the unpublished echidna and platypus genomes to investigate a group of metabolic genes and their evolution. This is following on from a study which found many genes involved in stomach function missing or changed in the platypus. It is likely that there are many other changes in monotreme metabolic genes that are yet to be investigated.
Yifei's Project: Expression patterns and functional characterisation of long non coding RNAs (lncRNAs) As one of the oldest living mammals, the platypus can provide insights into monotreme biology and give us insights into the evolution of the mammalian reproduction system. My current research is investigating the stage and cell type specific lncRNA in platypus spermatogenesis, in order to identify the restricted expression patterns of lncRNAs and work towards functional characterisation of those candidates in testis.
Praveena's Project: Understanding the role and evolution of long non-coding RNAs in monotreme reproduction Long non-coding RNAs (lncRNAs) are highly expressed in mammalian testis and they are likely to be involved in spermatogenesis. To understand the roles of lncRNAs in mammalian reproduction, it is important to study their expressions in the most basal clade of living mammals, monotremes. Monotremes have a fascinating reproductive system and studies show that there is a global transcriptional repression during spermatogenesis in monotremes. My research project is to identify monotreme testis-specific lncRNAs by utilizing the monotreme genome assemblies and a comprehensive transcriptome dataset using bioinformatics approaches. Additionally, my project also aimed to investigate the functions of lncRNAs in gene regulation during spermatogenesis in monotremes.