![Professor David Ascher](/sites/default/files/profiles/33027.jpeg)
Overview
Background
Prof David Ascher is currently an NHMRC Investigator and Director of the Biotechnology Program at the University of Queensland. He is also Head of Computational Biology and Clinical Informatics at the Baker Institute.
David’s research focus is in modelling biological data to gain insight into fundamental biological processes. One of his primary research interests has been developing tools to unravel the link between genotype and phenotype, using computational and experimental approaches to understand the effects of mutations on protein structure and function. His group has developed a platform of over 40 widely used programs for assessing the molecular consequences of coding variants (>7 million hits/year).
Working with clinical collaborators in Australia, Brazil and UK, these methods have been translated into the clinic to guide the diagnosis, management and treatment of a number of hereditary diseases, rare cancers and drug resistant infections.
David has a B.Biotech from the University of Adelaide, majoring in Biochemistry, Biotechnology and Pharmacology and Toxicology; and a B.Sci(Hon) from the University of Queensland, majoring in Biochemistry, where he worked with Luke Guddat and Ron Duggleby on the structural and functional characterization of enzymes in the branched-chain amino acid biosynthetic pathway. David then went to St Vincent’s Institute of Medical Research to undertake a PhD at the University of Melbourne in Biochemistry. There he worked under the supervision of Michael Parker using computational, biochemical and structural tools to develop small molecules drugs to improve memory.
In 2013 David went to the University of Cambridge to work with Sir Tom Blundell on using fragment based drug development techniques to target protein-protein interactions; and subsequently on the structural characterisation of proteins involved in non-homologous DNA repair. He returned to Cambridge in 2014 to establish a research platform to characterise the molecular effects of mutations on protein structure and function- using this information to gain insight into the link between genetic changes and phenotypes. He was subsequently recruited as a lab head in the Department of Biochemistry and Molecular Biology at the University of Melbourne in 2016, before joining the Baker Institute in 2019 and the University of Queensland in 2021.
He is an Associate Editor of PBMB and Fronteirs in Bioinformatics, and holds honorary positions at Bio21 Institute, Cambridge University, FIOCRUZ, and the Tuscany University Network.
Availability
- Professor David Ascher is:
- Available for supervision
- Media expert
Fields of research
Research impacts
We have successfully translated our computational tools into the clinic and industry, including:
- Clinical detection of drug resistance from whole-genome sequencing of pathogens, including Tuburculosis and Leprosy
- Genetic counselling for rare diseases and cancers with Addenbrooke's Hospital and Brazilian Ministry of Health
- Patient stratification within clinical trials
- Implementation within industry drug and biologics development programs
The tools we have developed have also been widely adopted within existing academic programs including:
- Integration of intermolecular interaction calculations using our tool Arpeggio in the PDBe, the European resource for the collection, organisation and dissemination of data on biological macromolecular structures.
- Integration of our missense tolerance scores within the widely used VEP tool for variant characterisation.
- Implementation of our resistance prediction tools within the London School of Hygiene & Tropical Medicine's TB-Profiler tool.
Works
Search Professor David Ascher’s works on UQ eSpace
2016
Journal Article
mCSM-lig: quantifying the effects of mutations on protein-small molecule affinity in genetic disease and emergence of drug resistance
Pires, Douglas E. V., Blundell, Tom L. and Ascher, David B. (2016). mCSM-lig: quantifying the effects of mutations on protein-small molecule affinity in genetic disease and emergence of drug resistance. Scientific Reports, 6 (1) 29575, 29575. doi: 10.1038/srep29575
2016
Journal Article
Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance
Phelan, Jody, Coll, Francesc, McNerney, Ruth, Ascher, David B., Pires, Douglas E. V., Furnham, Nick, Coeck, Nele, Hill-Cawthorne, Grant A., Nair, Mridul B., Mallard, Kim, Ramsay, Andrew, Campino, Susana, Hibberd, Martin L., Pain, Arnab, Rigouts, Leen and Clark, Taane G. (2016). Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance. BMC Medicine, 14 (1) 31, 31. doi: 10.1186/s12916-016-0575-9
2016
Journal Article
Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab′ Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity
Chan, Linda J., Ascher, David B., Yadav, Rajbharan, Bulitta, Jürgen B., Williams, Charlotte C., Porter, Christopher J. H., Landersdorfer, Cornelia B. and Kaminskas, Lisa M. (2016). Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab′ Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity. Molecular Pharmaceutics, 13 (4), 1229-1241. doi: 10.1021/acs.molpharmaceut.5b00749
2016
Journal Article
Tumour risks and genotype–phenotype–proteotype analysis of patients with germline mutations in the succinate dehydrogenase subunit genes SDHB, SDHC, and SDHD
Andrews, Katrina A, Vialard, Lindsey, Ascher, David B, Pires, Douglas E V, Bradshaw, Nicola, Cole, Trevor, Cook, Jackie, Irving, Richard, Kumar, Ajith, Lalloo, Fiona, Izatt, Louise, Goudie, David, Woodward, Emma R and Maher, Eamonn R (2016). Tumour risks and genotype–phenotype–proteotype analysis of patients with germline mutations in the succinate dehydrogenase subunit genes SDHB, SDHC, and SDHD. The Lancet, 387, S19-S19. doi: 10.1016/s0140-6736(16)00406-2
2016
Journal Article
In silico functional dissection of saturation mutagenesis: Interpreting the relationship between phenotypes and changes in protein stability, interactions and activity
Pires, Douglas E. V., Chen, Jing, Blundell, Tom L. and Ascher, David B. (2016). In silico functional dissection of saturation mutagenesis: Interpreting the relationship between phenotypes and changes in protein stability, interactions and activity. Scientific Reports, 6 (1) 19848. doi: 10.1038/srep19848
2016
Journal Article
Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy
Nemethova, Martina, Radvanszky, Jan, Kadasi, Ludevit, Ascher, David B., Pires, Douglas E. V., Blundell, Tom L., Porfirio, Berardino, Mannoni, Alessandro, Santucci, Annalisa, Milucci, Lia, Sestini, Silvia, Biolcati, Gianfranco, Sorge, Fiammetta, Aurizi, Caterina, Aquaron, Robert, Alsbou, Mohammed, Lourenço, Charles Marques, Ramadevi, Kanakasabapathi, Ranganath, Lakshminarayan R., Gallagher, James A., van Kan, Christa, Hall, Anthony K., Olsson, Birgitta, Sireau, Nicolas, Ayoob, Hana, Timmis, Oliver G., Sang, Kim-Hanh Le Quan, Genovese, Federica, Imrich, Richard ... Zatkova, Andrea (2016). Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy. European Journal of Human Genetics, 24 (1), 66-72. doi: 10.1038/ejhg.2015.60
2015
Journal Article
PEGylated interferon displays differences in plasma clearance and bioavailability between male and female mice and between female immunocompetent C57Bl/6J and athymic nude mice
Landersdorfer, Cornelia B., Caliph, Suzanne M., Shackleford, David M., Ascher, David B. and Kaminskas, Lisa M. (2015). PEGylated interferon displays differences in plasma clearance and bioavailability between male and female mice and between female immunocompetent C57Bl/6J and athymic nude mice. Journal of Pharmaceutical Sciences, 104 (5), 1848-1855. doi: 10.1002/jps.24412
2015
Journal Article
Lst4, the yeast Fnip1/2 orthologue, is a DENN-family protein
Pacitto, Angela, Ascher, David B, Wong, Louise H, Blaszczyk, Beata K, Nookala, Ravi K, Zhang, Nianshu, Dokudovskaya, Svetlana, Levine, Tim P and Blundell, Tom L (2015). Lst4, the yeast Fnip1/2 orthologue, is a DENN-family protein. Open Biology, 5 (12) 150174. doi: 10.1098/rsob.150174
2015
Journal Article
Exploring the chemical space of the lysine-binding pocket of the first kringle domain of hepatocyte growth factor/scatter factor (HGF/SF) yields a new class of inhibitors of HGF/SF-MET binding
Sigurdardottir, A G, Winter, A, Sobkowicz, A, Fragai, M, Chirgadze, D, Ascher, D B, Blundell, T L and Gherardi, E (2015). Exploring the chemical space of the lysine-binding pocket of the first kringle domain of hepatocyte growth factor/scatter factor (HGF/SF) yields a new class of inhibitors of HGF/SF-MET binding. Chemical Science, 6 (11), 6147-6157. doi: 10.1039/c5sc02155c
2015
Journal Article
Flexibility and small pockets at protein-protein interfaces: new insights into druggability
Jubb, Harry, Blundell, Tom L. and Ascher, David B. (2015). Flexibility and small pockets at protein-protein interfaces: new insights into druggability. Progress in Biophysics and Molecular Biology, 119 (1), 2-9. doi: 10.1016/j.pbiomolbio.2015.01.009
2015
Journal Article
Achieving high signal-to-noise in cell regulatory systems: spatial organization of multiprotein transmembrane assemblies of FGFR and MET receptors
Blaszczyk, Michal, Harmer, Nicholas J., Chirgadze, Dimitri Y., Ascher, David B. and Blundell, Tom L. (2015). Achieving high signal-to-noise in cell regulatory systems: spatial organization of multiprotein transmembrane assemblies of FGFR and MET receptors. Progress in Biophysics and Molecular Biology, 118 (3), 103-11. doi: 10.1016/j.pbiomolbio.2015.04.007
2015
Journal Article
Germline mutations in the CDKN2B tumor suppressor gene predispose to renal cell carcinoma
Jafri, Mariam, Wake, Naomi C, Ascher, David B, Pires, Douglas E V, Gentle, Dean, Morris, Mark R, Rattenberry, Eleanor, Simpson, Michael A, Trembath, Richard C, Weber, Astrid, Woodward, Emma R, Donaldson, Alan, Blundell, Tom L, Latif, Farida and Maher, Eamonn R (2015). Germline mutations in the CDKN2B tumor suppressor gene predispose to renal cell carcinoma. Cancer Discovery, 5 (7), 723-729. doi: 10.1158/2159-8290.CD-14-1096
2015
Journal Article
pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures
Pires, Douglas E V, Blundell, Tom L and Ascher, David B (2015). pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58 (9), 4066-72. doi: 10.1021/acs.jmedchem.5b00104
2015
Journal Article
Analysis of HGD gene mutations in patients with Alkaptonuria from the United Kingdom: identification of novel mutations
Usher, Jeannette L, Ascher, David B, Pires, Douglas E V, Milan, Anna M, Blundell, Tom L and Ranganath, Lakshminarayan R (2015). Analysis of HGD gene mutations in patients with Alkaptonuria from the United Kingdom: identification of novel mutations. JIMD Reports, 24, 3-11. doi: 10.1007/8904_2014_380
2015
Journal Article
PEGylation does not significantly change the initial intravenous or subcutaneous pharmacokinetics or lymphatic exposure of trastuzumab in rats but increases plasma clearance after subcutaneous administration
Chan, Linda J., Bulitta, Jürgen B., Ascher, David B., Haynes, John Michael, McLeod, Victoria M., Porter, Christopher J. H., Williams, Charlotte C. and Kaminskas, Lisa M. (2015). PEGylation does not significantly change the initial intravenous or subcutaneous pharmacokinetics or lymphatic exposure of trastuzumab in rats but increases plasma clearance after subcutaneous administration. Molecular Pharmaceutics, 12 (3), 794-809. doi: 10.1021/mp5006189
2015
Journal Article
Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumor-burdened lymph nodes after intravenous and subcutaneous administration in rats
Kaminskas, Lisa M., McLeod, Victoria M., Ascher, David B., Ryan, Gemma M., Jones, Seth, Haynes, John M., Trevaskis, Natalie L., Chan, Linda J., Sloan, Erica K., Finnin, Benjamin A., Williamson, Mark, Velkov, Tony, Williams, Elizabeth D., Kelly, Brian D., Owen, David J. and Porter, Christopher J. H. (2015). Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumor-burdened lymph nodes after intravenous and subcutaneous administration in rats. Molecular Pharmaceutics, 12 (2), 432-443. doi: 10.1021/mp500531e
2015
Journal Article
Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides
Hermans, Stefan J, Ascher, David B, Hancock, Nancy C, Holien, Jessica K, Michell, Belinda J, Chai, Siew Yeen, Morton, Craig J and Parker, Michael W (2015). Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides. Protein Science, 24 (2), 190-199. doi: 10.1002/pro.2604
2015
Book Chapter
Protein-protein interactions: structures and druggability
Ascher, David B., Jubb, Harry C., Pires, Douglas E. V., Ochi, Takashi, Higueruelo, Alicia and Blundell, Tom L. (2015). Protein-protein interactions: structures and druggability. Multifaceted roles of crystallography in modern drug discovery. (pp. 141-163) Dordrecht, Netherlands: Springer Netherlands. doi: 10.1007/978-94-017-9719-1_12
2015
Journal Article
Platinum: a database of experimentally measured effects of mutations on structurally defined protein-ligand complexes
Pires, Douglas E V, Blundell, Tom L and Ascher, David B (2015). Platinum: a database of experimentally measured effects of mutations on structurally defined protein-ligand complexes. Nucleic Acids Research, 43 (D1), D387-D391. doi: 10.1093/nar/gku966
2014
Journal Article
Practical lessons in murine thoracic lymph duct cannulations: Observations in female and male mice across four different strains that impact on cannulatability
Caliph, Suzanne M., Shackleford, David M., Ascher, David B. and Kaminskas, Lisa M. (2014). Practical lessons in murine thoracic lymph duct cannulations: Observations in female and male mice across four different strains that impact on cannulatability. Journal of Pharmaceutical Sciences, 104 (3), 1207-1209. doi: 10.1002/jps.24312
Funding
Current funding
Supervision
Availability
- Professor David Ascher is:
- Available for supervision
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Supervision history
Current supervision
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Doctor Philosophy
Developing structure-based deep learning methods to predict mutation effects on proteins
Principal Advisor
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Doctor Philosophy
Computer-aided drug design: predicting and mitigating drug toxicity
Principal Advisor
Other advisors: Dr Stephanie Portelli
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Doctor Philosophy
Exploring Cardiotoxicity Risk Factors
Principal Advisor
Other advisors: Dr Thanh-Binh Nguyen
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Doctor Philosophy
Post-transcriptional gene regulation: towards a better understanding of pathogenesis and medical applications
Principal Advisor
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Doctor Philosophy
Computational approaches to engineer and modulate G protein-coupled receptors
Principal Advisor
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Doctor Philosophy
Personalising treatments for genetic diseases
Principal Advisor
Other advisors: Dr Stephanie Portelli
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Doctor Philosophy
Deep Learning Algorithms for Polygenic Genotype-Phenotype Predictions and the development of genetics computation tools
Principal Advisor
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Doctor Philosophy
Towards the accurate functional characterisation of protein coding mutations
Principal Advisor
Other advisors: Dr Stephanie Portelli, Dr Thanh-Binh Nguyen
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Doctor Philosophy
Improving rational antibody design using machine learning
Principal Advisor
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Doctor Philosophy
Machine Learning for Protein Dynamics: Predicting Post-Translational Modifications and Mutation Effects
Principal Advisor
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Doctor Philosophy
Using Deep Learning in Cell & Gene Therapy
Principal Advisor
Other advisors: Dr Thanh-Binh Nguyen, Dr Stephanie Portelli
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Doctor Philosophy
Protein structure guided precision medicine
Principal Advisor
Other advisors: Professor Phil Hugenholtz, Dr Stephanie Portelli
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Doctor Philosophy
Rational protein engineering and inhibition
Principal Advisor
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Doctor Philosophy
Allosteric modulation of synaptic proteins by endogenous and modified sterols
Associate Advisor
Other advisors: Dr Evelyne Deplazes, Professor Megan O'Mara
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Doctor Philosophy
Breaking the chain of inflammation through targetting NLR proteins
Associate Advisor
Other advisors: Professor Avril Robertson
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Doctor Philosophy
Therapeutic Resolution of Inflammation in the Central Nervous System for Neuroprotection in Parkinson's Disease
Associate Advisor
Other advisors: Professor Avril Robertson
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Doctor Philosophy
Use of structural phylogeny and reconciliation in molecular phylogenetics
Associate Advisor
Other advisors: Dr Kate Bowerman, Professor Phil Hugenholtz
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Doctor Philosophy
Computational design of targeted lipid technologies
Associate Advisor
Other advisors: Professor Megan O'Mara
Media
Enquiries
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