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- A multi-pronged approach to targeting myeloproliferative neoplasms
- A new paradigm of machine learning-based structural variant detection
- A whole lot of junk or a treasure trove of discovery?
- Advanced imaging interrogation of pathogen induced NETosis
- Analysing the metabolic interactions in brain cancer
- Atopic dermatitis causes and treatments
- Boosting the efficacy of immunotherapy in lung cancer
- Building a cell history recorder using synthetic biology for longitudinal patient monitoring
- Characterisation of malaria parasite proteins exported into infected liver cells
- Deciphering the heterogeneity of the tissue microenvironment by multiplexed 3D imaging
- Defining the mechanisms of thymic involution and regeneration
- Delineating the molecular and cellular origins of liver cancer to identify therapeutic targets
- Developing computational methods for spatial transcriptomics data
- Developing drugs to block malaria transmission
- Developing models for prevention of hereditary ovarian cancer
- Developing statistical frameworks for analysing next generation sequencing data
- Development and mechanism of action of novel antimalarials
- Development of novel RNA sequencing protocols for gene expression analysis
- Discoveries in red blood cell production and function
- Discovering epigenetic silencing mechanisms in female stem cells
- Discovery and targeting of novel regulators of transcription
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Dissecting mechanisms of cytokine signalling
- Doublecortin-like kinases, drug targets in cancer and neurological disorders
- Epigenetic biomarkers of tuberculosis infection
- Epigenetics – genome wide multiplexed single-cell CUT&Tag assay development
- Exploiting cell death pathways in regulatory T cells for cancer immunotherapy
- Exploiting the cell death pathway to fight Schistosomiasis
- Finding treatments for chromatin disorders of intellectual disability
- Functional epigenomics in human B cells
- How do nutrition interventions and interruption of malaria infection influence development of immunity in sub-Saharan African children?
- Human lung protective immunity to tuberculosis
- Improving therapy in glioblastoma multiforme by activating complimentary programmed cell death pathways
- Innovating novel diagnostic tools for infectious disease control
- Integrative analysis of single cell RNAseq and ATAC-seq data
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigation of a novel cell death protein
- Malaria: going bananas for sex
- Mapping spatial variation in gene and transcript expression across tissues
- Mechanisms of Wnt secretion and transport
- Multi-modal computational investigation of single-cell communication in metastatic cancer
- Nanoparticle delivery of antibody mRNA into cells to treat liver diseases
- Naturally acquired immune response to malaria parasites
- Organoid-based discovery of new drug combinations for bowel cancer
- Organoid-based precision medicine approaches for oral cancer
- Removal of tissue contaminations from RNA-seq data
- Reversing antimalarial resistance in human malaria parasites
- Role of glycosylation in malaria parasite infection of liver cells, red blood cells and mosquitoes
- Screening for novel genetic causes of primary immunodeficiency
- Single-cell ATAC CRISPR screening – Illuminate chromatin accessibility changes in genome wide CRISPR screens
- Spatial single-cell CRISPR screening – All in one screen: Where? Who? What?
- Statistical analysis of single-cell multi-omics data
- Structural and functional analysis of epigenetic multi-protein complexes in genome regulation
- Structural basing for Wnt acylation
- Structure, dynamics and impact of extra-chromosomal DNA in cancer
- Targeted deletion of disease-causing T cells
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- Understanding Plasmodium falciparum invasion of red blood cells
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- Using combination immunotherapy to tackle heterogeneous brain tumours
- Using intravital microscopy for immunotherapy against brain tumours
- Using nanobodies to understand malaria invasion and transmission
- Using structural biology to understand programmed cell death
- Validation and application of serological markers of previous exposure to malaria
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Developing targeted protein degraders into innovative cancer medicines
A shared ambition to develop a new class of anti-cancer therapeutics has brought WEHI and Boehringer Ingelheim, a leading research-driven pharmaceutical company, together in an effort to ‘drug the undruggable’.
Founded in 1885, Boehringer Ingelheim is a global pharmaceutical company focused on developing innovative drugs in the areas of cardiometabolic diseases, immunology and respiratory research, central nervous system diseases, retinal health, and oncology and cancer immunology.
The collaboration between WEHI and Boehringer Ingelheim builds on pioneering discoveries made at WEHI over the past 25 years, to reveal the biology of a family of proteins known as the inhibitor of apoptosis proteins (IAPs) and their role in cell death.
Innovative approach
molecule (pink, centre) is developed that can destroy a
disease-causing protein (orange, left) by bringing it into
proximity with part of the cell’s protein recycling machinery
(multicoloured, right), such as an IAP protein.
Image generated by Dr Michael Roy using UCSF ChimeraX
A team involving laboratories across WEHI, led by cell death researcher Professor John Silke, will extend this knowledge to develop new therapeutics using an exciting new approach called targeted protein degradation.
Targeted protein degradation uses in-built protein recycling machinery within the cell to destroy a particular disease-causing protein of interest. In contrast, traditional drug discovery uses small molecule inhibitors to bind to proteins and block their action and is limited in its application to proteins with specific characteristics. Using targeted protein degradation, IAPs could also be harnessed to target other disease-causing proteins within the cell for destruction. It has the potential to dramatically expand the field of proteins that can be targeted by a therapeutic.
Professor Silke said he saw immense potential in this innovative approach. “We believe that, together with Boehringer Ingelheim, we can apply this novel IAP-based approach to a number of ‘undruggable’ disease targets that have proven intractable to more traditional drug discovery approaches. This collaboration will complement the drug discovery capabilities of the National Drug Discovery Centre at WEHI and expand our ability to translate research into new treatments for cancer.”
Academic-industry alliance to ‘drug the undruggable’
The partnership between WEHI and Boehringer Ingelheim combines broad and deep expertise in biology and therapeutic targeting of IAP proteins, protein degradation and drug discovery and development. The collaboration focuses on the generation of IAP-based protein degraders (IPDs) that can be used for therapeutic concept work and in vivo studies.
Head of Drug Discovery Sciences at Boehringer Ingelheim’s Vienna Research Site, Dr Peter Ettmayer, said he was looking forward to a fruitful collaboration.
“We have found unique, world-class scientific knowledge on the IAP family of proteins at WEHI. This partnership gives us the opportunity to leverage WEHI’s expertise and turn it into drug candidates through a collaborative program,” he said.
The three-year collaborative project will be conducted under the direction of a joint steering committee, leveraging existing capabilities and expertise within WEHI and Boehringer Ingelheim. Post collaboration, Boehringer Ingelheim will be responsible for further development, regulatory approvals and commercial activities while WEHI will receive milestone payments and royalties on sale. Financial terms of the collaboration remain undisclosed.
WEHI Head of Biotechnology and Commercialisation Dr Anne-Laure Puaux said the two organisations structured a sophisticated and mutually beneficial deal that established key business principles and laid the foundations for a strong relationship.
“This exciting collaborative program is a testament to our ability to work together with global industry partners to deliver potential ‘first-in-class’ drug candidates. Academic-industry partnerships hold immense potential for translating research discoveries into new treatments for patients,” Dr Puaux said.
Alliance Manager at Boehringer Ingelheim, Dr Karl-Heinz Heider, said the organisations had worked collaboratively to secure the deal.
“The alliance between WEHI and Boehringer Ingelheim was built upon insightful scientific discussions and has laid the foundations for a strong partnership built on trust between the two organisations,” he said.