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
2020
Journal Article
Exploring the structural distribution of genetic variation in SARS-CoV-2 with the COVID-3D online resource
Portelli, Stephanie, Olshansky, Moshe, Rodrigues, Carlos H. M., D’Souza, Elston N., Myung, Yoochan, Silk, Michael, Alavi, Azadeh, Pires, Douglas E. V. and Ascher, David B. (2020). Exploring the structural distribution of genetic variation in SARS-CoV-2 with the COVID-3D online resource. Nature Genetics, 52 (10), 999-1001. doi: 10.1038/s41588-020-0693-3
2020
Journal Article
EasyVS: a user-friendly web-based tool for molecule library selection and structure-based virtual screening
Pires, Douglas E V, Veloso, Wandré N P, Myung, YooChan, Rodrigues, Carlos H M, Silk, Michael, Rezende, Pâmela M, Silva, Francislon, Xavier, Joicymara S, Velloso, João P L, da Silveira, Carlos H and Ascher, David B (2020). EasyVS: a user-friendly web-based tool for molecule library selection and structure-based virtual screening. Bioinformatics, 36 (14), 4200-4202. doi: 10.1093/bioinformatics/btaa480
2020
Journal Article
mycoCSM: Using graph-based signatures to identify safe potent hits against Mycobacteria
Pires, Douglas E. V. and Ascher, David B. (2020). mycoCSM: Using graph-based signatures to identify safe potent hits against Mycobacteria. Journal of Chemical Information and Modeling, 60 (7), 3450-3456. doi: 10.1021/acs.jcim.0c00362
2020
Journal Article
mCSM-membrane: predicting the effects of mutations on transmembrane proteins
Pires, Douglas E V, Rodrigues, Carlos H M and Ascher, David B (2020). mCSM-membrane: predicting the effects of mutations on transmembrane proteins. Nucleic Acids Research, 48 (W1), W147-W153. doi: 10.1093/nar/gkaa416
2020
Journal Article
mmCSM-AB: guiding rational antibody engineering through multiple point mutations
Myung, Yoochan, Pires, Douglas E. V. and Ascher, David B. (2020). mmCSM-AB: guiding rational antibody engineering through multiple point mutations. Nucleic Acids Research, 48 (W1), W125-W131. doi: 10.1093/nar/gkaa389
2020
Journal Article
mCSM-AB2: guiding rational antibody design using graph-based signatures
Myung, Yoochan, Rodrigues, Carlos H. M., Ascher, David B. and Pires, Douglas E. V. (2020). mCSM-AB2: guiding rational antibody design using graph-based signatures. Bioinformatics, 36 (5), 1453-1459. doi: 10.1093/bioinformatics/btz779
2020
Journal Article
Structure guided prediction of Pyrazinamide resistance mutations in pncA
Karmakar, Malancha, Rodrigues, Carlos H. M., Horan, Kristy, Denholm, Justin T. and Ascher, David B. (2020). Structure guided prediction of Pyrazinamide resistance mutations in pncA. Scientific Reports, 10 (1) 1875, 1875. doi: 10.1038/s41598-020-58635-x
2020
Journal Article
Widespread remodeling of proteome solubility in response to different protein homeostasis stresses
Sui, Xiaojing, Pires, Douglas E V, Ormsby, Angelique R, Cox, Dezerae, Nie, Shuai, Vecchi, Giulia, Vendruscolo, Michele, Ascher, David B, Reid, Gavin E and Hatters, Danny M (2020). Widespread remodeling of proteome solubility in response to different protein homeostasis stresses. Proceedings of the National Academy of Sciences of the United States of America, 117 (5), 2422-2431. doi: 10.1073/pnas.1912897117
2020
Journal Article
Variant type is associated with disease characteristics in SDHB, SDHC and SDHD-linked phaeochromocytoma-paraganglioma
Bayley, Jean Pierre, Bausch, Birke, Rijken, Johannes Adriaan, van Hulsteijn, Leonie Theresia, Jansen, Jeroen C., Ascher, David, Pires, Douglas Eduardo Valente, Hes, Frederik J., Hensen, Erik F., Corssmit, Eleonora P. M., Devilee, Peter and Neumann, Hartmut P. H. (2020). Variant type is associated with disease characteristics in SDHB, SDHC and SDHD-linked phaeochromocytoma-paraganglioma. Journal of Medical Genetics, 57 (2), 96-103. doi: 10.1136/jmedgenet-2019-106214
2020
Journal Article
Computational saturation mutagenesis to predict structural consequences of systematic mutations in the beta subunit of RNA polymerase in
Vedithi, Sundeep Chaitanya, Rodrigues, Carlos H. M., Portelli, Stephanie, Skwark, Marcin J., Das, Madhusmita, Ascher, David B., Blundell, Tom L. and Malhotra, Sony (2020). Computational saturation mutagenesis to predict structural consequences of systematic mutations in the beta subunit of RNA polymerase in . Computational and Structural Biotechnology Journal, 18, 271-286. doi: 10.1016/j.csbj.2020.01.002
2020
Journal Article
Covalent inactivation of Mycobacterium thermoresistibile inosine-5'-monophosphate dehydrogenase (IMPDH)
Trapero, Ana, Pacitto, Angela, Chan, Daniel Shiu-Hin, Abell, Chris, Blundell, Tom L., Ascher, David B. and Coyne, Anthony G. (2020). Covalent inactivation of Mycobacterium thermoresistibile inosine-5'-monophosphate dehydrogenase (IMPDH). Bioorganic and Medicinal Chemistry Letters, 30 (2) 126792, 126792. doi: 10.1016/j.bmcl.2019.126792
2020
Book Chapter
A comprehensive computational platform to guide drug development using graph-based signature methods
Pires, Douglas E. V., Portelli, Stephanie, Rezende, Pâmela M., Veloso, Wandré N. P., Xavier, Joicymara S., Karmakar, Malancha, Myung, Yoochan, Linhares, João P. V., Rodrigues, Carlos H. M., Silk, Michael and Ascher, David B. (2020). A comprehensive computational platform to guide drug development using graph-based signature methods. Structural bioinformatics: methods and protocols. (pp. 91-106) New York, NY, United States: Humana. doi: 10.1007/978-1-0716-0270-6_7
2019
Journal Article
Hyper transmission of Beijing lineage Mycobacterium tuberculosis: systematic review and meta-analysis
Karmakar, Malancha, Trauer, James M, Ascher, David B and Denholm, Justin T (2019). Hyper transmission of Beijing lineage Mycobacterium tuberculosis: systematic review and meta-analysis. The Journal of Infection, 79 (6), 572-581. doi: 10.1016/j.jinf.2019.09.016
2019
Journal Article
dendPoint: a web resource for dendrimer pharmacokinetics investigation and prediction
Kaminskas, Lisa M., Pires, Douglas E. V. and Ascher, David B. (2019). dendPoint: a web resource for dendrimer pharmacokinetics investigation and prediction. Scientific Reports, 9 (1) 15465, 15465. doi: 10.1038/s41598-019-51789-3
2019
Journal Article
Large expert-curated database for benchmarking document similarity detection in biomedical literature search
Brown, Peter, Tan, Aik-Choon, El-Esawi, Mohamed A., Liehr, Thomas, Blanck, Oliver, Gladue, Douglas P., Almeida, Gabriel M. F., Cernava, Tomislav, Sorzano, Carlos O., Yeung, Andy W. K., Engel, Michael S., Chandrasekaran, Arun Richard, Muth, Thilo, Staege, Martin S., Daulatabad, Swapna V., Widera, Darius, Zhang, Junpeng, Meule, Adrian, Honjo, Ken, Pourret, Olivier, Yin, Cong-Cong, Zhang, Zhongheng, Cascella, Marco, Flegel, Willy A., Goodyear, Carl S., van Raaij, Mark J., Bukowy-Bieryllo, Zuzanna, Campana, Luca G., Kurniawan, Nicholas A. ... RELISH Consortium (2019). Large expert-curated database for benchmarking document similarity detection in biomedical literature search. Database-The Journal of Biological Databases and Curation, 2019 ARTN baz085, 1-67. doi: 10.1093/database/baz085
2019
Journal Article
Nedd8 hydrolysis by UCH proteases in Plasmodium parasites
Karpiyevich, Maryia, Adjalley, Sophie, Mol, Marco, Ascher, David B., Mason, Bethany, van der Heden van Noort, Gerbrand J., Laman, Heike, Ovaa, Huib, Lee, Marcus C. S. and Artavanis-Tsakonas, Katerina (2019). Nedd8 hydrolysis by UCH proteases in Plasmodium parasites. PLoS Pathogens, 15 (10), e1008086. doi: 10.1371/journal.ppat.1008086
2019
Journal Article
ProCarbDB: a database of carbohydrate-binding proteins
Copoiu, Liviu, Torres, Pedro H M, Ascher, David B, Blundell, Tom L and Malhotra, Sony (2019). ProCarbDB: a database of carbohydrate-binding proteins. Nucleic Acids Research, 48 (D1), D368-D375. doi: 10.1093/nar/gkz860
2019
Journal Article
A family of dual-activity glycosyltransferase-phosphorylases mediates mannogen turnover and virulence in Leishmania parasites
Sernee, M. Fleur, Ralton, Julie E., Nero, Tracy L., Sobala, Lukasz F., Kloehn, Joachim, Vieira-Lara, Marcel A., Cobbold, Simon A., Stanton, Lauren, Pires, Douglas E. V., Hanssen, Eric, Males, Alexandra, Ward, Tom, Bastidas, Laurence M., van der Peet, Phillip L., Parker, Michael W., Ascher, David B., Williams, Spencer J., Davies, Gideon J. and McConville, Malcolm J. (2019). A family of dual-activity glycosyltransferase-phosphorylases mediates mannogen turnover and virulence in Leishmania parasites. Cell Host and Microbe, 26 (3), 385-399.e9. doi: 10.1016/j.chom.2019.08.009
2019
Journal Article
Synthesis and structure-activity relationship of 1-(5-isoquinolinesulfonyl)piperazine analogues as inhibitors of Mycobacterium tuberculosis IMPDH
Singh, Vinayak, Pacitto, Angela, Donini, Stefano, Ferraris, Davide M, Boros, Sándor, Illyés, Eszter, Szokol, Bálint, Rizzi, Menico, Blundell, Tom L, Ascher, David B, Pato, Janos and Mizrahi, Valerie (2019). Synthesis and structure-activity relationship of 1-(5-isoquinolinesulfonyl)piperazine analogues as inhibitors of Mycobacterium tuberculosis IMPDH. European Journal of Medicinal Chemistry, 174, 309-329. doi: 10.1016/j.ejmech.2019.04.027
2019
Journal Article
mCSM-PPI2: predicting the effects of mutations on protein–protein interactions
Rodrigues, Carlos H. M., Myung, Yoochan, Pires, Douglas E. V. and Ascher, David B. (2019). mCSM-PPI2: predicting the effects of mutations on protein–protein interactions. Nucleic Acids Research, 47 (W1), W338-W344. doi: 10.1093/nar/gkz383
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
Unravelling the Physicochemical Drivers of Biomolecular Self-Assembly though Multiscale Simulations
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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