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Regulation Of TNF Expression In Inflammation And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$728,447.00
Summary
By studying a spontaneous mutation in mice, we have found an error in the TNF gene (a major factor in many inflammatory diseases) that causes severe arthritis, heart valve disease and gut inflammation. We have also identified new regulators of TNF expression, which might be useful therapeutic targets to limit inflammation. We intend to study the role of these regulators in controlling the expression of TNF, and the link between chronic inflammation and the development of cancer.
Deadly Commute - Targeting The Trafficking Mechanisms That Licence Inflammatory Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$774,544.00
Summary
MLKL is a protein naturally found inside cells. MLKL is activated by inflammation. Once activated, MLKL relocates to the outer periphery of cells and kills them. Gut cells are especially vulnerable to death-by-MLKL and this problem causes Inflammatory Bowel Disease. Using cutting edge microscopy, we have discovered how MLKL moves to the periphery of cells prior to killing them. We will test if blocking this movement of MLKL to the cell periphery stops gut death and Inflammatory Bowel Disease.
New Drug Combinations To Enhance Elimination Of Hepatitis B Infection
Funder
National Health and Medical Research Council
Funding Amount
$888,304.00
Summary
We have developed a therapy that kills hepatitis B virus infected cells and promotes elimination of infection. We are now testing novel drugs that can be used to maximise the efficacy of our new treatment to promote better outcomes that may be translated to other infections.
Improving Outcomes For Cancer Patients By Targeting The Epigenome
Funder
National Health and Medical Research Council
Funding Amount
$2,258,892.00
Summary
The most commonly mutated proteins in cancer involve so called epigenetic regulators, a class of proteins that regulate access to our DNA to control gene expression, DNA repair and replication. We and others have recently developed a variety of drugs to help inhibit the aberrant activity of these epigenetic proteins. My research will focus on ways to improve the efficacy of these existing drugs and find new epigenetic therapies to improve the survival of patients with a broad range of cancers.
Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time t ....Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time the cardiac regulatory repertoire in zebrafish and will compare it with that of fly and mouse using cutting-edge bioinformatics pipelines. This work will unravel cardiac-specific regulatory modifications that give rise to evolutionary changes. On a broader scale, it will shed new light on the role of regulatory innovations over gene innovations in the emergence of new traits.Read moreRead less
Developing the Dunnart as a Model Species for Marsupial Research. The project aims to develop a marsupial model capable of genome manipulations to take our understanding of marsupial biology to the next level. In doing so, the project would produce the first comprehensive transcriptome data defining early cell lineage specification in a marsupial. Combined with similar data from mouse and human, it would enable us to examine diversity in early mammals. In addition, it would identify cohorts of g ....Developing the Dunnart as a Model Species for Marsupial Research. The project aims to develop a marsupial model capable of genome manipulations to take our understanding of marsupial biology to the next level. In doing so, the project would produce the first comprehensive transcriptome data defining early cell lineage specification in a marsupial. Combined with similar data from mouse and human, it would enable us to examine diversity in early mammals. In addition, it would identify cohorts of genes with fundamental roles in differentiation of the earliest cell lineages: trophoblast, pluriblast and hypoblast. The project may identify maternally localised transcripts with a marsupial-specific role in trophoblast–pluriblast specification, giving new insights into the fundamental pathways maintaining pluripotency in mammals and the evolution of the mammalian genome.Read moreRead less
The developmental and evolutionary origins of vertebrate fins and limbs. This project aims to investigate the origin of paired appendages, a major event in early vertebrate history that changed ecological opportunity and fuelled the radiation of jawed vertebrates. This project expects to generate new knowledge on the mechanism that drove this innovation, which despite over a century of debate, remains one
of the great unknowns of comparative vertebrate evolution. Expected outcomes of this projec ....The developmental and evolutionary origins of vertebrate fins and limbs. This project aims to investigate the origin of paired appendages, a major event in early vertebrate history that changed ecological opportunity and fuelled the radiation of jawed vertebrates. This project expects to generate new knowledge on the mechanism that drove this innovation, which despite over a century of debate, remains one
of the great unknowns of comparative vertebrate evolution. Expected outcomes of this project include uncovering the anatomical changes underpinning the origin of the vertebrate appendicular system. This should provide significant benefits as it will inform our own natural history and provide a paradigm for studying gene network
conservation, phylogenetic modifications, and the acquisition of novel structures.Read moreRead less
Genomic Analysis Of DNA Binding And Gene Regulation By The Chromatin Remodelling Factor UBF
Funder
National Health and Medical Research Council
Funding Amount
$624,254.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is the major anabolic event of a growing cell and is frequently dysregulated during disease such as cancer. This grant will examine a protein termed UBF that we think plays an important role in orchestrating the cellular response to dysregulated ribosome biogenesis. By understanding how UBF functions we hope to uncover novel therapeutic approaches to treat diseases associated with ribosome stress .
Cytotoxic lymphocytes are immune cells responsible for the killing infected or cancerous cells. How cytotoxic lymphocytes mature from a naive inactive to a fully activated state as they encounter infected or malignant cells is poorly understood, and will be investigated in the current proposal. Our results will aid in the development of novel therapies for cancer and other immunological diseases.
Leveraging Genomics Strategies To Generate Adult Neurons From IPSCs And Somatic Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,593,336.00
Summary
Recent advances have made it possible to derive myriad specialized human cells from stem cells or by directly reprogramming cell identity. However, these derived cells are generally arrested at a fetal developmental stage, and do not mature to function like adult cells. We will use new genomic, epigenetic, cell reprogramming, and manipulation methods to discover how to derive mature cells, aiming to generate mature neurons for use in neurobiology research, disease modeling, and drug screening.