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- 6 cysteine proteins key mediators between malaria parasites and human host
- A balancing act of immunity: autoimmunity versus malignancies
- Activating https://www.wehi.edu.au/node/add/individual-student-research-page#Parkin to treat Parkinson’s disease
- Analysing single cell technologies to understand breast cancer
- Bioinformatics methods for detecting and making sense of somatic genomic rearrangements
- Characterising new regulators in inflammatory signalling pathways
- Computational melanoma genomics
- Control of human lymphocyte cell expansion in complex immune diseases
- Deciphering biophysical changes in red blood cell membrane during malaria parasite infection
- Deciphering the signalling functions of pseudokinases
- Deep profiling of blood cancers during targeted therapy
- Determining the mechanism of type I cytokine receptor triggering
- Differential expression analysis of RNA-seq using multivariate variance modelling
- Discovering new genetic causes of primary antibody deficiencies
- Discovery of novel drug combinations for the treatment of bowel cancer
- Drug targets and compounds that block growth of malaria parasites
- Effects of nutrition on immunity and infection in Asia and Africa
- Enabling deubiquitinase drug discovery
- Epigenetic drivers of immune cell function
- Epigenetic regulation of systemic iron homeostasis
- Exploiting cell death pathways in regulatory T cells for cancer immunotherapy
- Fatal attraction: how apoptotic pore assembly is governed during mitochondrial cell death
- Genomic instability and the immune microenvironment in lung cancer
- How do T lymphocytes decide their fate?
- How the epigenetic regulator SMCHD1 works and how to target it to treat disease
- Human lung protective immunity to tuberculosis: host-environment systems biology
- Human monoclonal antibodies against malaria infection
- Identifying novel treatment options for ovarian carcinosarcoma
- Inflammasome activation in autoinflammatory disease
- Investigating mechanisms of cell death and survival using zebrafish
- Investigating microbial natural products with anti-protozoal activity
- Investigating the role of mutant p53 in cancer
- Investigating the role of platelets in motor neuron disease
- Mapping DNA repair networks in cancer
- Molecular mechanisms controlling embryonic lung progenitor cells
- Nanobodies against malaria
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- New approaches to treat cancer and inflammatory disease using the ubiquitin system
- Next generation CRISPR screens using iPSC
- Novel cell death and inflammatory modulators in lupus
- Programming T cells to defend against infections
- Restraining cytokine-receptor signalling in myeloproliferative neoplasms
- Screening for regulators of jumping genes
- Statistical analysis of genome-wide chromatin organisation using Hi-C
- Statistical analysis of trapped-ion-mobility time-of-flight mass spectrometry proteomics data
- Structure and function of E3 ubiquitin ligases
- Target identification of potent antimalarial agents
- The mitochondrial TOM complex in neurodegenerative disease
- The molecular mechanisms underlying Kir4.1 activity in gliomas
- The role of differential splicing in the genesis of breast cancer
- Uncovering the roles of long non-coding RNAs in human bowel cancer
- Understanding malaria infection dynamics
- Understanding the function of the E3 ligase Parkin in Parkinson’s disease
- Understanding the molecular basis of chromosome instability in gastric cancer
- Utilising pre-clinical models to discover novel therapies for tuberculosis
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Ruth Kluck-Projects
Researcher:
Understanding mitochondrial pore formation during apoptotic cell death
A key event in apoptotic cell death is the oligomerisation of the BAX and BAK proteins to form pores in mitochondria, although how they form pores is still unclear.
We recently found that cells lacking the putative trafficking protein PACS1 are resistant to apoptosis due to unusual complexes of BAX and BAK (Brasacchio et al, Cell Death Differ, 2017).
We are thus characterising the unusual BAX and BAK complexes in PACS1-knockdown cells to understand this new means of resistance.
Elucidating how homodimers of BAX and of BAK form the apoptotic pore
As the formation of BAX and BAK homo-oligomers strongly correlates with their ability to perforate mitochondria, defining how BAX and BAK dimers self-associate and interact with the membrane will reveal how they trigger apoptosis.
Our data indicate that dimers do not interact by distinct protein-protein interface, but form disordered clusters to generate pores (Uren et al, eLife, 2017; Uren et al, Philos Trans R Soc Lond B Biol Sci, 2017).
A range of biochemical approaches will examine further how the outer membrane is involved in oligomerisation of dimers.
Determining how MCL-1 contributes to resistance during anti-cancer treatment
Inhibition of apoptosis by prosurvival BCL-2 proteins contributes to oncogenesis and to resistance to cancer treatments. In particular, MCL-1 can cause resistance by sequestering activated BAK.
We aim to better understand when and how MCL-1 and BAK interact in different cancer cells following treatment, and so identify ways of circumventing this resistance.
Delivering antibodies into cells to trigger apoptotic cell death
We found that an antibody to the BAK protein can trigger its activation leading to mitochondrial pore formation and cell death (Iyer et al, Nat Commun 2016 7:11734).
To investigate if this antibody can be developed as a novel anti-cancer agent, this project will combine the anti-BAK antibody with others that can be taken up by cancer cells, and test for induction of cell death.