David was a PhD student in Professor Kathryn (Kat) Holt's group.
Professor Terry O'Brien, Head of Central Clinical School and Professor Robyn Slattery on behalf of Professor Kat Holt both spoke at the ceremony.
David enrolled in the PhD at Monash, after completing a Masters in Bioinformatics under the supervision of Professor Kathryn Holt.
During his Masters David wrote a hugely influential article, the Beginner's guide to comparative bacterial genome analysis using next-generation sequence data, that has helped more than 167K scientists globally. He also developed the default program today for identifying genomic variation in bacterial pathogens, RedDog, which is still the gold standard in the field.
He enrolled in the PhD 21 February 2019, initially under the supervision of Professor Kathryn Holt, Sebastian Duchene and Bernard Pope, later adding Professor Anton Peleg when Kathryn went on maternity leave.
David's thesis, entitled In Silico Discovery of Single Nucleotide Polymorphisms Under Positive Parallel Selection in Bacteria, concentrated on the question of how infectious diseases evolve convergent mutations. That is, how drug resistance appears in distinct bacteria, for example. This is one of the most pressing problems in infectious disease research today, as acknowledged by the World Health Organisation and others.
To address the problem of how drug resistance emerges he developed a mathematical and computational method, SNPPar, that actually identifies the emergence and convergence of such harmful mutations, an approach that has become widely used globally. At the time of his passing he was investigating drug resistance in Tuberculosis and had made groundbreaking contributions to our understanding of how various important bacterial pathogens spread and cause disease, including those that lead to enteric, respiratory, and bloodborne infections.
During his candidature he was progressing well with his research, with the panel chair of his progress review noting Mr Edwards demonstrated a sound understanding of his research project. His presentation highlighted clear aims, data output and rationale for future experiments.
With the assistance of the supervisory team, David’s thesis, entitled “In Silico Discovery of Single Nucleotide Polymorphisms Under Positive Parallel Selection in Bacteria”, was assembled and went under examination earlier this year, with the University ratifying the award 16 August 2022.
The quality of David’s work can be evidenced by comments from the two examiners, both highly regarded experts in the field:
- The text provided in thesis is overall written to a high level. There is a clear understanding of the biology of convergent evolution.
- Overall, I think the work presented shows that the author was operating at a high level of research capability and already understood a lot of the aspects of their thesis topic. I am very confident that a full thesis would have been produced to a very high standard. I must congratulate the supervisors on their work both putting this document together and on the work achieved with the candidate.
- This thesis contains many excellent pieces of work. I have absolutely no doubt that had David lived, he would have gone on to complete a PhD thesis of the very highest order.
- The combination of chapters 1-3 show beyond any doubt that David was a student of great ability. He very clearly understood the literature in great depth, he was able to write complex and (most importantly!) useful software that has propelled his field forwards, and he was able to apply all of this knowledge and new software to answer key pure and applied questions in evolutionary biology. I have absolutely no hesitation in concluding that had he lived, he would have produced an outstanding thesis.
Thesis Summary
Bacterial pathogens are continuously evolving; most changes are deleterious or neutral, but sometimes a mutation leads to functional change. Such mutations are so very rarely beneficial, that when they do arise in parallel in distantly related isolates (known as homoplasy) it implies that the change is likely positively selected because it confers an adaptive advantage to the bacteria. In this thesis a method is developed to identify and characterise potential homoplasies within a target bacterial population, using large-scale whole-genome data; the method is then applied the method to investigate patterns of positive selection in Mycobacterium tuberculosis.
From David's primary supervisor, Professor Kat Holt
Professor Slattery read some words provided by Professor Holt who was not able to be there in person.
David was the first student I ever supervised - beginning in 2010, as a MSc (Bioinformatics) project student at University of Melbourne, co-supervised with Bernie Pope (who later joined me in co-supervising David’s PhD).
David’s MSc project was establishing our lab’s pipeline for microbial genomics analysis - the pipeline was dubbed RedDog, after our mutual love of Australian sheep dogs.
After completing his MSc project in 2012, I hired David as a casual research assistant to continue developing the RedDog pipeline. In this role David contributed to lots of projects, and helped to get new lab members up to speed with bioinformatics analyses.
David was a fixture of the lab for years and share with us his love of dogs, cats and cycling (staying up to watch the Tour de France). Together David and I co-authored the “Beginner’s Guide to Comparative Bacterial Genomics” - a review and tutorial published in 2013 that is world-renowned in our field, it has been accessed >160k times (89 formal cites, which is remarkable for a tutorial).
In 2017, having been a valued lab member for 7 years, David decided he was ready to embark on a PhD and we enlisted Bernie Pope and Sebastian Duchene to co-supervise (while still at Melbourne Uni).
David had great respect for Bernie from the beginning (first encountered when Bernie was teaching Python programming to him as a MSc Bioinformatics student), and admired Sebastian hugely for his expertise in evolutionary biology and a shared love of cycling.
In 2018 when I announced to the group that I was moving to Monash, David didn’t bat an eyelid - he supported the move, me, and the new alignment to more clinically focused work, and happily transferred his enrolment to Monash (although very keen to retain Bernie and Sebastian as UniMelb co-supervisors).
David's first first-author paper for his PhD came back from peer-review weeks before his death - ultimately it was posthumously accepted in the journal Microbial Genomics in 2021.
David was on track to complete a stellar thesis, he was enthusiastic but never certain of himself, always keen to discuss and re-work and refine until he got things right - the attention to detail that’s so important for a scientist.
His passing came as a huge shock to myself and the rest of the lab.
Professor Robyn Slattery said, "I wish to reiterate my thanks to you all for making the award ceremony for David such a special occasion. I know how much this will have meant to his family and colleagues. Kat's words were really appreciated, as was the tremendous effort made by her team and co supervisors. The effort you all made speaks volumes about the positive culture of collegiate and student life in Monash's medical faculty and the Central Clinical School."
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