Ellisdon Lab research
About Dr Andrew Ellisdon
Dr Ellisdon is Head of the Structural Biology of Signalling and Cancer Laboratory and Senior Research Fellow at the Monash Biomedicine Discovery Institute (BDI). Dr Ellisdon obtained his PhD in 2007 at Monash University before training in structural biology as a Marie-Curie and EMBO Fellow at the MRC Laboratory of Molecular Biology (LMB) in Cambridge, UK. His team has a particular research focus on capturing an atomic resolution view of “signalling in action” by observing protein complexes formed by critical tumour-suppressor proteins and oncogenes. This resolution is enabled by combining recent advances in single-particle cryo-electron microscopy with crystallography and classical biochemistry.
1. Structural regulation of GEF and GAP complexes in cancer signalling
The development of new strategies for treating metastases, and therapeutics specifically targeting the aberrant cellular signalling pathways of the metastatic process, is of great importance. RhoGTPases are small G protein members of the Ras superfamily that regulate cytoskeletal organization, cell-cycle progression and gene expression, and their dysregulation drives tumourigenesis and metastatic dissemination. Guanine-nucleotide-exchange factors (GEFs) turn on signalling by catalysing the exchange of GDP for GTP on target G-proteins, whereas GTPase-activating proteins (GAPs) terminate signalling by promoting GTP hydrolysis. We are focused on gaining key structural insights into the imbalance between GEF and GAP activity that dysregulates many cancer-associated signalling pathways.
2. Molecular mechanism of the TSC; a master switch of cell growth
The Tuberous Sclerosis Complex (TSC) is formed by TSC1 (also termed hamartin), TSC2 (also termed tuberin), and TBC1 domain family member 7 (TBC1D7). Mutation of either TSC1 or TSC2 genes results in the autosomal dominant genetic disorder TSC (also termed tuberous sclerosis or epiloia) that affects approximately 2 million people worldwide. The disorder is characterised by the formation of tumours in a range of organs and tissues including the brain, heart, kidneys, skin, and lungs. We are undertaking an integrative structural biology program to elucidate the structure of the TSC and the molecular basis of its dysregulation in disease.
3. Translating IL-1 family cytokines to the clinic
Interleukin-1 (IL-1) family cytokines play key roles in the initiation and regulation of innate immunity and inflammation. As part of a multidisciplinary team the reaches from the lab bench to the clinic, our laboratory is coupling structural biology with protein engineering techniques to drive new intellectual property development to translate the anti-inflammatory activity of IL-1 family cytokines to the clinic. Publications from the collaboration include studies in Science Immunology (Ellisdon et al, 2017) and Nature Immunology (Nold-Petry et al, 2015). These discoveries, and a strong IP position on the back of key structural findings, have led to a major continuing international research and licensing agreement with Roche and key investments from the Medical Research Commercialisation Fund (MRCF).
Visit Dr Ellisdon's Monash research profile to see a full listing of current projects.
We utilise a range of structural biology techniques including protein crystallography, single-particle cryoEM, cross-linking and mass-spectrometry, H/D exchange mass-spectrometry and NMR within the laboratory. Expression systems available within the laboratory include yeast, bacterial, insect, and mammalian cells allowing us to purify even the most intricate multi-component protein complexes.
We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).
Professor Marcel Nold, Hudson Institute
Associate Professor Hans Elmlund, Monash University
Dr Michelle Halls, Monash Institute of Pharmaceutical Sciences
Associate Professor Claudia Nold, Hudson Institute
Professor Christina Mitchell, Monash University
Professor Eric Morand, School of Clinical Sciences at Monash Health
Associate Professor Gerry Hammond, University of Pittsburgh
Student research projects
The Ellisdon Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.
Please visit Supervisor Connect to explore the projects currently available in our Lab.