Overview
Background
Prof David Ascher is currently an NHMRC Investigator, immediate past Director of the Biotechnology Program, and Deputy Associate Dean (Research Partnerships) in the Faculty of Science 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
2018
Journal Article
Fragment-based approach to targeting inosine-5'-monophosphate dehydrogenase (IMPDH) from Mycobacterium tuberculosis
Trapero, Ana, Pacitto, Angela, Singh, Vinayak, Sabbah, Mohamad, Coyne, Anthony G, Mizrahi, Valerie, Blundell, Tom L, Ascher, David B and Abell, Chris (2018). Fragment-based approach to targeting inosine-5'-monophosphate dehydrogenase (IMPDH) from Mycobacterium tuberculosis. Journal of Medicinal Chemistry, 61 (7), 2806-2822. doi: 10.1021/acs.jmedchem.7b01622
2018
Journal Article
Structural implications of mutations conferring rifampin resistance in Mycobacterium leprae
Vedithi, Sundeep Chaitanya, Malhotra, Sony, Das, Madhusmita, Daniel, Sheela, Kishore, Nanda, George, Anuja, Arumugam, Shantha, Rajan, Lakshmi, Ebenezer, Mannam, Ascher, David B, Arnold, Eddy and Blundell, Tom L (2018). Structural implications of mutations conferring rifampin resistance in Mycobacterium leprae. Scientific Reports, 8 (1) 5016. doi: 10.1038/s41598-018-23423-1
2018
Journal Article
Evolution of carbapenem resistance in Acinetobacter baumannii during a prolonged infection
Hawkey, Jane, Ascher, David B, Judd, Louise M, Wick, Ryan R, Kostoulias, Xenia, Cleland, Heather, Spelman, Denis W, Padiglione, Alex, Peleg, Anton Y and Holt, Kathryn E (2018). Evolution of carbapenem resistance in Acinetobacter baumannii during a prolonged infection. Microbial Genomics, 4 (3) 000165. doi: 10.1099/mgen.0.000165
2018
Book Chapter
Prediction and optimization of pharmacokinetic and toxicity properties of the ligand
Pires, Douglas E. V., Kaminskas, Lisa M. and Ascher, David B. (2018). Prediction and optimization of pharmacokinetic and toxicity properties of the ligand. Computational Drug Discovery and Design. (pp. 271-284) New York, NY United States: Humana Press. doi: 10.1007/978-1-4939-7756-7_14
2017
Journal Article
A computational approach from gene to structure analysis of the human ABCA4 transporter involved in genetic retinal diseases
Trezza, Alfonso, Bernini, Andrea, Langella, Andrea, Ascher, David B, Pires, Douglas E V, Sodi, Andrea, Passerini, Ilaria, Pelo, Elisabetta, Rizzo, Stanislao, Niccolai, Neri and Spiga, Ottavia (2017). A computational approach from gene to structure analysis of the human ABCA4 transporter involved in genetic retinal diseases. Investigative Ophthalmology and Visual Science, 58 (12), 5320-5328. doi: 10.1167/iovs.17-22158
2017
Journal Article
Optimizing genomic medicine in epilepsy through a gene-customized approach to missense variant interpretation
Traynelis, Joshua, Silk, Michael, Wang, Quanli, Berkovic, Samuel F, Liu, Liping, Ascher, David B, Balding, David J and Petrovski, Slavé (2017). Optimizing genomic medicine in epilepsy through a gene-customized approach to missense variant interpretation. Genome Research, 27 (10), 1715-1729. doi: 10.1101/gr.226589.117
2017
Journal Article
Mutations at protein-protein interfaces: small changes over big surfaces have large impacts on human health
Jubb, Harry C, Pandurangan, Arun P, Turner, Meghan A, Ochoa-Montaño, Bernardo, Blundell, Tom L and Ascher, David B (2017). Mutations at protein-protein interfaces: small changes over big surfaces have large impacts on human health. Progress in Biophysics and Molecular Biology, 128, 3-13. doi: 10.1016/j.pbiomolbio.2016.10.002
2017
Journal Article
Combating mutations in genetic disease and drug resistance: understanding molecular mechanisms to guide drug design
Albanaz, Amanda T S, Rodrigues, Carlos H M, Pires, Douglas E V and Ascher, David B (2017). Combating mutations in genetic disease and drug resistance: understanding molecular mechanisms to guide drug design. Expert Opinion on Drug Discovery, 12 (6), 553-563. doi: 10.1080/17460441.2017.1322579
2017
Journal Article
SDM: a server for predicting effects of mutations on protein stability
Pandurangan, Arun Prasad, Ochoa-Montaño, Bernardo, Ascher, David B. and Blundell, Tom L. (2017). SDM: a server for predicting effects of mutations on protein stability. Nucleic Acids Research, 45 (W1), W229-W235. doi: 10.1093/nar/gkx439
2017
Journal Article
DNA-PKcs, allostery, and DNA double-strand break repair: defining the structure and setting the stage
Chirgadze, Dimitri Y, Ascher, David B, Blundell, Tom L and Sibanda, Bancinyane L (2017). DNA-PKcs, allostery, and DNA double-strand break repair: defining the structure and setting the stage. Methods in Enzymology, 592, 145-157. doi: 10.1016/bs.mie.2017.04.001
2017
Journal Article
Dimeric but not monomeric α-lactalbumin potentiates apoptosis by up regulation of ATF3 and reduction of histone deacetylase activity in primary and immortalised cells
Sharp, Julie A, Brennan, Amelia J, Polekhina, Galina, Ascher, David B, Lefevre, Christophe and Nicholas, Kevin R (2017). Dimeric but not monomeric α-lactalbumin potentiates apoptosis by up regulation of ATF3 and reduction of histone deacetylase activity in primary and immortalised cells. Cellular Signalling, 33, 86-97. doi: 10.1016/j.cellsig.2017.02.007
2017
Journal Article
SDHA related tumorigenesis: a new case series and literature review for variant interpretation and pathogenicity
Casey, Ruth T, Ascher, David B, Rattenberry, Eleanor, Izatt, Louise, Andrews, Katrina A, Simpson, Helen L, Challis, Benjamen, Park, Soo-Mi, Bulusu, Venkata R, Lalloo, Fiona, Pires, Douglas E V, West, Hannah, Clark, Graeme R, Smith, Philip S, Whitworth, James, Papathomas, Thomas G, Taniere, Phillipe, Savisaar, Rosina, Hurst, Laurence D, Woodward, Emma R and Maher, Eamonn R (2017). SDHA related tumorigenesis: a new case series and literature review for variant interpretation and pathogenicity. Molecular Genetics and Genomic Medicine, 5 (3), 237-250. doi: 10.1002/mgg3.279
2017
Journal Article
Huntingtin inclusions trigger cellular quiescence, deactivate apoptosis, and lead to delayed necrosis
Ramdzan, Yasmin M., Trubetskov, Mikhail M., Ormsby, Angelique R., Newcombe, Estella A., Sui, Xiaojing, Tobin, Mark J., Bongiovanni, Marie N., Gras, Sally L., Dewson, Grant, Miller, Jason M. L., Finkbeiner, Steven, Moily, Nagaraj S., Niclis, Jonathan, Parish, Clare L., Purcell, Anthony W., Baker, Michael J., Wilce, Jacqueline A., Waris, Saboora, Stojanovski, Diana, Bocking, Till, Ang, Ching-Seng, Ascher, David B., Reid, Gavin E. and Hatters, Danny M. (2017). Huntingtin inclusions trigger cellular quiescence, deactivate apoptosis, and lead to delayed necrosis. Cell Reports, 19 (5), 919-927. doi: 10.1016/j.celrep.2017.04.029
2017
Journal Article
Genomes, structural biology and drug discovery: combating the impacts of mutations in genetic disease and antibiotic resistance
Pandurangan, Arun Prasad, Ascher, David B., Thomas, Sherine E. and Blundell, Tom L. (2017). Genomes, structural biology and drug discovery: combating the impacts of mutations in genetic disease and antibiotic resistance. Biochemical Society Transactions, 45 (2), 303-311. doi: 10.1042/BST20160422
2017
Journal Article
mCSM–NA: predicting the effects of mutations on protein–nucleic acids interactions
Pires, Douglas E.V. and Ascher, David B. (2017). mCSM–NA: predicting the effects of mutations on protein–nucleic acids interactions. Nucleic Acids Research, 45 (W1), W241-W246. doi: 10.1093/nar/gkx236
2017
Journal Article
Familial germline mutation defines a new human cohesinopathy
Soardi, Fernanda C, Machado-Silva, Alice, Linhares, Natália D, Zheng, Ge, Qu, Qianhui, Pena, Heloísa B, Martins, Thaís M M, Vieira, Helaine G S, Pereira, Núbia B, Melo-Minardi, Raquel C, Gomes, Carolina C, Gomez, Ricardo S, Gomes, Dawidson A, Pires, Douglas E V, Ascher, David B, Yu, Hongtao and Pena, Sérgio D J (2017). Familial germline mutation defines a new human cohesinopathy. NPJ Genomic Medicine, 2 (1) 7. doi: 10.1038/s41525-017-0009-4
2017
Journal Article
Arpeggio: a web server for calculating and visualising interatomic interactions in protein structures
Jubb, Harry C, Higueruelo, Alicia P, Ochoa-Montaño, Bernardo, Pitt, Will R, Ascher, David B and Blundell, Tom L (2017). Arpeggio: a web server for calculating and visualising interatomic interactions in protein structures. Journal of Molecular Biology, 429 (3), 365-371. doi: 10.1016/j.jmb.2016.12.004
2017
Journal Article
DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair
Sibanda, Bancinyane L, Chirgadze, Dimitri Y, Ascher, David B and Blundell, Tom L (2017). DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair. Science, 355 (6324), 520-524. doi: 10.1126/science.aak9654
2017
Journal Article
Glutathione transferase P1-1 as an arsenic drug-sequestering enzyme
Parker, Lorien J., Bocedi, Alessio, Ascher, David B., Aitken, Jade B., Harris, Hugh H., Lo Bello, Mario, Ricci, Giorgio, Morton, Craig J. and Parker, Michael W. (2017). Glutathione transferase P1-1 as an arsenic drug-sequestering enzyme. Protein Science, 26 (2), 317-326. doi: 10.1002/pro.3084
2017
Journal Article
The inosine monophosphate dehydrogenase, GuaB2, is a vulnerable new bactericidal drug target for tuberculosis
Singh, Vinayak, Donini, Stefano, Pacitto, Angela, Sala, Claudia, Hartkoorn, Ruben C., Dhar, Neeraj, Keri, Gyorgy, Ascher, David B., Mondésert, Guillaume, Vocat, Anthony, Lupien, Andréanne, Sommer, Raphael, Vermet, Hélène, Lagrange, Sophie, Buechler, Joe, Warner, Digby F., McKinney, John D., Pato, Janos, Cole, Stewart T., Blundell, Tom L., Rizzi, Menico and Mizrahi, Valerie (2017). The inosine monophosphate dehydrogenase, GuaB2, is a vulnerable new bactericidal drug target for tuberculosis. ACS Infectious Diseases, 3 (1), 5-17. doi: 10.1021/acsinfecdis.6b00102
Supervision
Availability
- Professor David Ascher is:
- Available for supervision
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Supervision history
Current supervision
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Doctor Philosophy
Computational approaches to engineer and modulate G protein-coupled receptors
Principal Advisor
-
Doctor Philosophy
Exploring Cardiotoxicity Risk Factors
Principal Advisor
Other advisors: Dr Thanh-Binh Nguyen
-
Doctor Philosophy
Developing structure-based deep learning methods to predict mutation effects on proteins
Principal Advisor
-
Doctor Philosophy
Exploring Cardiotoxicity Risk Factors
Principal Advisor
Other advisors: Dr Thanh-Binh Nguyen
-
Master Philosophy
Explore the dark spots in PDB
Principal Advisor
-
Doctor Philosophy
Post-transcriptional gene regulation: towards a better understanding of pathogenesis and medical applications
Principal Advisor
-
Doctor Philosophy
Exploring Cardiotoxicity Risk Factors
Principal Advisor
Other advisors: Dr Thanh-Binh Nguyen
-
Doctor Philosophy
Computational approaches to engineer and modulate G protein-coupled receptors
Principal Advisor
-
Doctor Philosophy
Personalising treatments for genetic diseases
Principal Advisor
Other advisors: Dr Stephanie Portelli
-
Doctor Philosophy
Deep Learning Algorithms for Polygenic Genotype-Phenotype Predictions and the development of genetics computation tools
Principal Advisor
-
Doctor Philosophy
Computer-aided drug design: predicting and mitigating drug toxicity
Principal Advisor
Other advisors: Dr Stephanie Portelli
-
Doctor Philosophy
Towards the accurate functional characterisation of protein coding mutations
Principal Advisor
Other advisors: Dr Stephanie Portelli, Dr Thanh-Binh Nguyen
-
Doctor Philosophy
Improving rational antibody design using machine learning
Principal Advisor
-
Doctor Philosophy
Harnessing AlphaFold and explainable AI to better characterise human missense variants and diseases
Principal Advisor
Other advisors: Dr Stephanie Portelli, Dr Thanh-Binh Nguyen
-
Doctor Philosophy
Machine Learning for Protein Dynamics: Predicting Post-Translational Modifications and Mutation Effects
Principal Advisor
-
Doctor Philosophy
Using Deep Learning in Cell & Gene Therapy
Principal Advisor
Other advisors: Dr Stephanie Portelli
-
Doctor Philosophy
Protein structure guided precision medicine
Principal Advisor
Other advisors: Professor Phil Hugenholtz, Dr Stephanie Portelli
-
Master Philosophy
Explore the dark spots in PDB
Principal Advisor
-
Doctor Philosophy
Rational protein engineering and inhibition
Principal Advisor
-
Doctor Philosophy
Post-transcriptional gene regulation: towards a better understanding of pathogenesis and medical applications
Principal Advisor
-
Doctor Philosophy
Unravelling the Physicochemical Drivers of Biomolecular Self-Assembly though Multiscale Simulations
Associate Advisor
Other advisors: Dr Evelyne Deplazes, Professor Megan O'Mara
-
Doctor Philosophy
Breaking the chain of inflammation through targetting NLR proteins
Associate Advisor
Other advisors: Professor Avril Robertson
-
Doctor Philosophy
Therapeutic Resolution of Inflammation in the Central Nervous System for Neuroprotection in Parkinson's Disease
Associate Advisor
Other advisors: Professor Avril Robertson
-
Doctor Philosophy
Use of structural phylogeny and reconciliation in molecular phylogenetics
Associate Advisor
Other advisors: Dr Kate Bowerman, Professor Phil Hugenholtz
-
Doctor Philosophy
Therapeutic Resolution of Inflammation in the Central Nervous System for Neuroprotection in Parkinson's Disease
Associate Advisor
Other advisors: Professor Avril Robertson
-
Doctor Philosophy
Computational design of targeted lipid technologies
Associate Advisor
Other advisors: Professor Megan O'Mara
Completed supervision
-
2025
Doctor Philosophy
Computational approaches to engineer and modulate G protein-coupled receptors
Principal Advisor
Media
Enquiries
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