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Most of Ashburner's research has been on the model organism Drosophila melanogaster. Ashburner's career began in the early period of molecular biology prior to the development of most of the recombinant DNA techniques in use today, such as Northern/Southern/Western blotting. Nevertheless, by observing patterns of "puffing" in polytene chromosomes, he established the existence of a cascade of genetic controls in the post-larval development triggered by ecdysone. The Ashburner model of 1974 became a paradigm for metazoan gene regulation inasmuch as the Jacob-Monod model did for prokaryotes. Ashburner collaborated widely and mentored numerous PhD students and Postdoctoral research students during his career.
Ashburner was also an early pioneer in the application of computers to biology. His contributions include his active participation in setting up FlyBase and the development of Open Biomedical Ontologies to allow machine-searchable annotation of biological information, particularly the Gene Ontology and ChEBI. He was instrumental in establishing the EBI, as well as securing its location in the UK, and acted as the first head of the EBI jointly with Graham Cameron.
Open science advocacy
As part of his involvement the sequencing of the D. melanogaster genome, Ashburner played an instrumental role in ensuring that the resulting sequence and annotations would be made publicly available. Additionally, Ashburner made a strong case for the human genome published in Science in 2000 by Celera Genomics to be made freely available, and has spoken out repeatedly against the privatization of genomic resources. Ashburner was also one of the signatories of the first open letter to Science in 2001 calling for a centralized, open repository of the scientific literature, and subsequently became a strong advocate of Open Access publishing, speaking out for this cause in the scientific literature and popular media. He also provided written evidence to the UK Parliament Select Committee on Science and Technology supporting Open Access publishing and served on the initial advisory board of UK PubMed Central, the first global mirror site of the PubMed Central repository of freely available biological literature.
"Distinguished for his wide-ranging researches on the cytology, genetics and evolution of Drosophila melanogaster. He was the first to make a comprehensive map of puffs in the salivary gland polytene chromosomes and to define the stage at which each was expressed. He went on to demonstrate the effects of various stimuli, especially heat-shock and ecdysone, on puffing at specific loci, and correlated particular puffs with particular gene products. Combining genetic, cytological and molecular methodology, he has investigated in fine detail particular chromosome regions, especially that surrounding the Adh (alcohol dehydrogenase) gene, revealing many novel features of structure and function. He has also made important contributions to the understanding of evolution and speciation within the D.melanogaster group of species. Ashburner has unique standing as a scholar and authority in the whole area of Drosophila research."
^Adams, M.; Celniker, S.; Holt, R.; Evans, C.; Gocayne, J.; Amanatides, P.; Scherer, S.; Li, P.; Hoskins, R.; Galle, R. F.; George, R. A.; Lewis, S. E.; Richards, S.; Ashburner, M.; Henderson, S. N.; Sutton, G. G.; Wortman, J. R.; Yandell, M. D.; Zhang, Q.; Chen, L. X.; Brandon, R. C.; Rogers, Y. H.; Blazej, R. G.; Champe, M.; Pfeiffer, B. D.; Wan, K. H.; Doyle, C.; Baxter, E. G.; Helt, G.; et al. (2000). "The genome sequence of Drosophila melanogaster". Science. 287 (5461): 2185-2195. Bibcode:2000Sci...287.2185.. CiteSeerX10.1.1.549.8639. doi:10.1126/science.287.5461.2185. PMID10731132.
^Hill, R. J.; Billas, I. M. L.; Bonneton, F. O.; Graham, L. D.; Lawrence, M. C. (2013). "Ecdysone Receptors: From the Ashburner Model to Structural Biology*". Annual Review of Entomology. 58: 251-271. doi:10.1146/annurev-ento-120811-153610. PMID23072463.