The Preiss group studies the mechanisms and transcriptome-wide patterns of eukaryotic mRNA translation its regulation by RNA-binding proteins and non-coding RNA (e.g., microRNAs) as a means of controlling gene activity.
Translation takes place on the ribosome and is aided by numerous accessory factors. Failure to properly regulate the translation of specific mRNAs is linked to a growing spectrum of diseases. We investigate post-transcriptional gene control in mammalian and yeast cell culture models and employ a mix of conventional molecular biology approaches as well as global methods such as next generation sequencing.
Eyras' group works at the intersection between genomics technologies and biomedical research. The team develops computational tools to analyse and interpret data from new genomic platforms. By applying these technologies to patient samples, Eyras’ research has enabled new insights into basic mechanisms of RNA processing and its role in human disease. Eyras’ group includes computer scientists and biologists developing new algorithms and machine learning tools to address standing problems in RNA biology.
The Gardiner group works towards “Investigating and understanding how ribosomal biogenesis controls and biases haematopoiesis”. RNA Polymerase (Pol I) synthesises the ribosomal RNAs (rRNAs) which form the nucleic acid backbone of the ribosomes; a process which is rate limiting for all cellular growth. Pol I transcription is consistently dysregulated in cancer, and drugs co-developed by our team which selectively target Pol I are showing great promise in the clinic as novel cancer therapies. Unexpectedly, the Gardiner group (in collaboration with the Hannan group) have discovered that Pol I inhibitors also have a unique haematopoietic properties. That is, treatment of mice or humans with Pol I inhibitors results in a rapid changes in circulating blood cells. Our data demonstrate this is an on-target effect mediated though the role Pol I transcription plays in regulating cell stemness and differentiation. Our work aims to establish mechanism of action, and evaluate a range of related compounds and their activity plus safety profiles.
The Hayashi group investigates the ‘Transposon defence mechanism’ in animals. Transposons are selfish genetic elements present in every eukaryotic genome. The evolutionally conserved small RNA called piRNA silences transposons in animal gonads. Using Drosophila as a model, we are dissecting the mechanism of piRNA biogenesis to understand the logic of its selectivity towards transposon. We use Drosophila genetics, basic molecular & cell biology, such as immuno-precipitation, immuno-staining, illumina and Nanopore sequencing. We are also highly specialised in sequencing small RNAs and the accompanying computational analyses (see 10.1038/nature20162).
The Natoli group investigates ‘the role of miRNA and exosomes in retinal degenerations’. Age-related macular degeneration (AMD) is the leading cause of vision loss in the Western World, characterized by the progressive death of the light-sensing photoreceptor cells and retinal pigment epithelium (RPE), resulting in irreversible blindness. For the most prevalent form of AMD, geographic atrophy (GA) or more commonly known dry AMD, there are no available treatments. We are devising both diagnostic and therapeutic strategies using extracellular vesicles (EV) including exosomes, and their molecular cargo including miRNA to improve health outcomes for patients with AMD.
The Tremethick group has demonstrated that the exchange of the core histone H2A with its variant forms, in particular the essential histone variant H2A.Z, Mechanistically, we demonstrated that H2A.Z, and other types of H2A variants, performs these crucial functions by directly regulating the extent of chromatin compaction. Recently, we have also found that histone H2A variants are located at intron-exon boundaries to regulate pre-mRNA splicing, which is critical for male fertility and brain function. Moreover, we have found that the mis-incorporation of histone H2A variants into chromatin plays an important role in the progression of cancer.
To further understand the role of the epigenome, including the role of histone variants, in regulating genome function, we have established long-range genome mapping and computational 3D genome modelling approaches, which revealed how active and inactive genes are packaged and segregated into different 3-dimensional compartments within a chromosome during the differentiation of human stem cells.
The Shirokikh group’s main approach is to precisely define the types of rapid cell responses by analysing the gene-specific levels of translation on the background of transcription for each response and cell type. To achieve this, we use a suit of ‘high throughput’ RNA and protein methods of broad discovery combined with computational biology and create our own techniques.
Translational responses are of a highest interest to us as they provide an insight into the underexplored areas of flexibility and adaptability of life. Dysregulated translation is pertinent to a multitude of disorders and serves as the core of the cells’ metabolic regulation and maintains homeostasis and cell proliferation decisions appropriate to the external and internal environments. As such, it is critical for the rapid mitigation of stress damage, age-related diseases and cancer.
Motivated by its importance for life, we wish to investigate questions of basic biology of dynamic protein synthesis control as well as its applied health- and method-focused problems.
Dr Amee George leads the ANU Centre for Therapeutic Discovery at the John Curtin School of Medical Research and is a Fellow in the ACRF Department of Cancer Biology and Therapeutics at ANU. She is an expert in high-throughput functional (RNAi/CRISPR) and compound screening approaches (primarily high-content imaging-based), and she uses these approaches to investigate nucleolar biology and signalling pathways, diseases of the ribosome (ribosomopathies) as well as cancer, with a view to developing new therapeutics which target the nucleolus in these diseases.
Bacteriophages are the most abundant virus on our planet and have this unique ability to subvert bacterial defence. Our laboratory aims in elucidating the mechanisms of antiphage immune defence in bacteria, including CRISPR. Using a multidisciplinary approach (computational biology, biochemistry, microbiology and RNA biology) we have developed a unique approach to uncover novel antiphage defence systems, mechanically dissect the nuclease activity of antiphage effectors (including CRISPR) and harnessing those as the next generation of gene editing tools. Besides a fundamental understanding of antiphage defence mechanisms in bacteria, our goal is to expand the CRISPR toolbox and develop more precise gene editing tools.
Dr Quinn’s research uses Drosophila molecular genetic approaches to determine how transcriptional networks integrate extra- and intracellular signalling inputs to drive tissue growth. Deciphering pathways controlling growth during normal development provides an avenue to understanding dysregulation of these networks in cancer.
The major research focus in the Fischer lab is to understand the connection between chromatin structure, pervasive transcription and RNA surveillance, and their influence on genomic stability and disease development, especially in cancer and aging-related diseases. In addition, the lab is pursuing synthetic biology approaches to develop early detection and novel treatment methods in cancer.
Professor Ross Hannan's work focuses on the molecular analysis of major pro-malignant transcription factor networks that operate in cancer cells using an integrated approach that combines cell biology, genomics, proteomics, biochemistry, genetics, bioinformatics and strong interactions with oncologists in the clinic. Through this molecular understanding, he hopes to identify key therapeutic nodes to impede the progression of aggressive cancers. The availability of ribosomes is a fundamental rate-limiting step for tumour cell proliferation. He is examining the genetic and epigenetic processes by which ribosomal RNA gene transcription, is regulated by RNA Polymerase I, and how this process is dysregulated during cancer. A second area of research focuses on how bidirectional communication between cytosolic signaling networks and chromatin-associated protein complexes regulate RNA Polymerase II gene expression programs driving cellular traits associated with high-grade malignancies. Key cancer streams studied are haematological, melanoma, colorectal, ovarian and prostate.
Cellular origin of lymphoma: Recent studies have elucidated recurrent somatic mutations in several subtypes of non-Hodgkin lymphoma. However, it is not yet known at what stage in ontogeny these mutations arise. Our group is studying the disease heterogeneity within subtypes of non-Hodgkin lymphoma using sophisticated multicolour flow cytometry, genotyping and ultra-deep sequencing techniques. The project involves use of human samples archived in the Haematology research tissue bank, and direct translation of research findings into the diagnostic laboratory and clinic.