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- A new regulator of stemness to create dendritic cell factories for immunotherapy
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- Developing a new drug that targets plasmacytoid dendritic cells for the treatment of lupus
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- Investigating the role of mutant p53 in cancer
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- Modelling spatial and demographic heterogeneity of malaria transmission risk
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- Predicting the effect of non-coding structural variants in cancer
- Structural basis of catenin-independent Wnt signalling
- Structure and biology of proteins essential for Toxoplasma parasite invasion
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- Targeting the immune microenvironment to treat KRAS-mutant adenocarcinoma
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Tony Papenfuss-Projects
Researcher:
Tumour evolution and heterogeneity
Tumour evolution underlies metastasis and the development of resistance to treatment. Focusing particularly on melanoma, we are studying the evolution of a variety of cancers using different technologies. This requires the development of new statistical tools to identify evolutionary changes between tumour genomes, including changes in subclonal populations.
Team members: Vincent Corbin, Ismael Vergara, Leon di Stefano
Genomic rearrangements in tumour genomes
We are developing methods to detect and genotype genomic fusions in tumours, and applying these to understand the mechanisms underlying structural variation in tumour genomes. We are particularly interested in complex rearrangements and recently discovered the dynamic mechanisms underlying the formation of highly rearranged neochromosomes, which required mathematical models to make sense of the data.
We previously developed Socrates, a sensitive breakpoint prediction method that identifies clusters soft-clipped reads. We have applied this to a variety of cancer-types and used it to map transgene insertion sites.
Resource: Socrates program available at http://bioinf.wehi.edu.au/socrates
Team members: Jan Schröder, Daniel Cameron, Leon di Stefano
Scabies mite genome project
Scabies is a skin infection caused by the parasitic mite, Sarcoptes scabiei. Scabies affects about 100 million people worldwide. Scabies is a major health problem in Aboriginal and Torres Strait Islander communities, where co-infection of scabies wounds by bacteria is thought to be the main cause of high rates of rheumatic heart disease.
To accelerate research into scabies mite biology and its health impact in these communities, we are sequencing the genome, transcriptome and microbiome of the scabies mite using a variety of sequencing platforms. We will analyse the scabies genome and compare it with the genomes of other mites to identify essential, conserved genomic features.
Team member: Ehtesham Mofiz
Mechanistic and functional drivers of neochromosome evolution
Neochromosomes are massive, extra chromosomes found in 3 per cent of cancers, but are common in some cancer types, such as liposarcomas.
Neochromosomes harbor the oncogenic changes that drive these cancers. We recently mapped the structure of neochromosomes at high resolution. This revealed that punctuated chromothriptic events and hundreds of breakage-fusion-bridge (BFB) cycles underlie their formation (Garsed et al, Cancer Cell 2014).
We are now pursuing the molecular machinery that contributes to this process.
Team member: Alan Rubin