Aled Edwards

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Aled Edwards (born June 1, 1962) is the founder and Chief Executive of the Structural Genomics Consortium, a charitable public-private partnership. He is Professor of Medical Genetics and Medical Biophysics at the University of Toronto, Visiting Professor of Chemical Biology at the University of Oxford, and Adjunct Professor at McGill University.

Early life[edit]

Born in Holyhead, Wales, Edwards moved to Canada in 1965 with his parents Undeg and Iwan Edwards, a choral conductor who was awarded the Order of Canada in 1995 for his contributions to Canadian music.[1]

Education[edit]

Edwards earned his bachelor's degree (1983) and his Ph.D. (1988) in biochemistry from McGill University supervised by Peter Braun.  He carried out post-doctoral studies at Stanford University in the laboratory of Roger Kornberg, where he first crystallized RNA polymerase II,[2][3][4][5] a structure for which Kornberg was awarded the Nobel Prize in Chemistry in 2006.

Research contributions[edit]

From 1992 to 1997, while a professor at McMaster University, Edwards became interested in developing structural biology methods and was among the first to use mass spectrometry to identify regions of proteins prone to crystallization.[6]  He used this technique to facilitate the crystallography of key proteins involved in DNA replication and repair[7][8][9] before becoming interested in applying this and other methods to carry out structural biology on a proteome scale.

In 1997, now at the University of Toronto, Edwards, together with his colleague Cheryl Arrowsmith, collaborated to launch one of the first projects in structural genomics, and soon published one of the papers that defined this new field.[10] As a central player in the Protein Structure Initiative, their Toronto team contributed to more than a thousand new microbial protein structures over the next decade, developed new crystallization methods,[11][12] and used structural methods to de-orphanize several nuclear receptors[13][14] and study ion transport across membranes.[15]

As of 2019, Edwards has co-contributed more datasets to the Protein Data Bank than any other scientist.[16]

Business activities[edit]

In the late 1990’s, Edwards co-founded and served as CEO of Borealis Biosciences and Chalon Biotech, which he merged to form Affinium Pharmaceuticals, a Toronto-based company. Affinium developed afabicin, a novel narrow-spectrum antibiotic that is now in clinical development at DebioPharm.  Several other companies have been spun out of his research programs, including Harbinger Biotechnology and Engineering, which was acquired by Epiphyte3, and 1DegreeBio, which was acquired by LabX Media Group.  

More recently, Edwards founded M4K Pharma, a company that is developing a brain-penetrant drug targeting the ALK2 kinase, in order to treat children with incurable diffuse-intrinsic pontine glioma (DIPG).  The novel open science business model[17] being developed by M4K Pharma allows its science to be disclosed on an ongoing basis, and for any approved drug to be priced affordably. Edwards serves on the Board of the Agora Open Science Trust.

Open science and science policy[edit]

Open Science[edit]

Edwards is considered one of the pioneers of open science,[18] particularly as it applied to biomedicine and drug discovery.  Since 2003, all human protein structural information derived from the SGC has been placed into the public domain, prior to publication and without restriction on use.  In 2007, he, together with Richard Gold, created the SGC Open Science Principles, under which the SGC became the first biomedical research organization to adopt open science principles that mandated sharing and eschewed patenting on any activity, including novel chemistry. In 2016, Edwards both spearheaded the Open Lab Notebook initiative, which now comprises over 20 scientists sharing their experiments as they are done, as well as collaborated with Guy Rouleau at the Montreal Neurological Institute (The Neuro) to create the concept of an open research institute. That collaboration led to the formation of the Tanenbaum Open Science Institute,[19] and to the broader institutional commitment of The Neuro to open science. In 2017, Edwards and colleagues conceptualized an open trust mechanism to share research reagents,[20] and the SGC has been using this mechanism since.  Finally, in 2018, Edwards, Max Morgan and Owen Roberts launched the world’s first open science drug discovery company, M4K (Meds for Kids) Pharma, and developed a business model that is consistent with open science and affordable pricing. In 2019, Morgan and Edwards launched M4ND Pharma, to tackle neurological diseases using open drug discovery approaches.  For his leadership role in promoting open access drug discovery, Edwards was named a Senior Ashoka Fellow in 2015.[21]

Science and innovation policy[edit]

On the 10th anniversary of the publication of the draft sequence of the human genome, Edwards and colleagues were asked for their perspective. Their “Roads not Taken” paper,[22] which quantified the “under-studied” parts of the human genome, has led to a number of funding initiatives, including the Illuminating the Druggable Genome initiative[23] at the NIH, and presaged a number of studies that examine the unintended consequences of the peer-review system.[24]

Edwards is a champion of science reproducibility, focusing considerable attention on the quality of research reagents[25] and the need for transparent standards. 

Edwards has also contributed to science communication; he served as the scientific advisor for the Gemini Award-winning television series ReGenesis.

Personal[edit]

Edwards has been married to Elizabeth Edwards since 1985, and they have three children and one grandchild.  Elizabeth is director of BioZone and Professor of Chemical Engineering and Applied Chemistry at the University of Toronto, and winner of Canada’s 2016 Killam Prize for Engineering, among other awards.  She is the daughter of Leonhard and Jeanne Wolfe, who was awarded the Order of Canada in 2009 for her contributions to Canadian planning.[26] Aled’s brother, Owain Edwards, is an entomologist at CSIRO in Australia.

References[edit]

  1. ^ "Order of Canada". archive.gg.ca. Retrieved 2019-07-12.
  2. ^ Edwards, A. M.; Darst, S. A.; Feaver, W. J.; Thompson, N. E.; Burgess, R. R.; Kornberg, R. D. (March 1990). "Purification and lipid-layer crystallization of yeast RNA polymerase II". Proceedings of the National Academy of Sciences of the United States of America. 87 (6): 2122–2126. Bibcode:1990PNAS...87.2122E. doi:10.1073/pnas.87.6.2122. ISSN 0027-8424. PMC 53638. PMID 2179949.
  3. ^ Darst, S. A.; Edwards, A. M.; Kubalek, E. W.; Kornberg, R. D. (1991-07-12). "Three-dimensional structure of yeast RNA polymerase II at 16 A resolution". Cell. 66 (1): 121–128. doi:10.1016/0092-8674(91)90144-n. ISSN 0092-8674. PMID 2070414.
  4. ^ Darst, S. A.; Kubalek, E. W.; Edwards, A. M.; Kornberg, R. D. (1991-09-05). "Two-dimensional and epitaxial crystallization of a mutant form of yeast RNA polymerase II". Journal of Molecular Biology. 221 (1): 347–357. doi:10.1016/0022-2836(91)80223-h. ISSN 0022-2836. PMID 1920413.
  5. ^ Cramer, P.; Bushnell, D. A.; Fu, J.; Gnatt, A. L.; Maier-Davis, B.; Thompson, N. E.; Burgess, R. R.; Edwards, A. M.; David, P. R. (2000-04-28). "Architecture of RNA polymerase II and implications for the transcription mechanism". Science. 288 (5466): 640–649. Bibcode:2000Sci...288..640C. doi:10.1126/science.288.5466.640. ISSN 0036-8075. PMID 10784442.
  6. ^ Barwell, J. A.; Bochkarev, A.; Pfuetzner, R. A.; Tong, H.; Yang, D. S.; Frappier, L.; Edwards, A. M. (1995-09-01). "Overexpression, purification, and crystallization of the DNA binding and dimerization domains of the Epstein-Barr virus nuclear antigen 1". The Journal of Biological Chemistry. 270 (35): 20556–20559. doi:10.1074/jbc.270.35.20556. ISSN 0021-9258. PMID 7657632.
  7. ^ Bochkarev, A.; Barwell, J. A.; Pfuetzner, R. A.; Furey, W.; Edwards, A. M.; Frappier, L. (1995-10-06). "Crystal structure of the DNA-binding domain of the Epstein-Barr virus origin-binding protein EBNA 1". Cell. 83 (1): 39–46. doi:10.1016/0092-8674(95)90232-5. ISSN 0092-8674. PMID 7553871.
  8. ^ Bochkarev, A.; Barwell, J. A.; Pfuetzner, R. A.; Bochkareva, E.; Frappier, L.; Edwards, A. M. (1996-03-08). "Crystal structure of the DNA-binding domain of the Epstein-Barr virus origin-binding protein, EBNA1, bound to DNA". Cell. 84 (5): 791–800. doi:10.1016/s0092-8674(00)81056-9. ISSN 0092-8674. PMID 8625416.
  9. ^ Bochkarev, A.; Pfuetzner, R. A.; Edwards, A. M.; Frappier, L. (1997-01-09). "Structure of the single-stranded-DNA-binding domain of replication protein A bound to DNA". Nature. 385 (6612): 176–181. Bibcode:1997Natur.385..176B. doi:10.1038/385176a0. ISSN 0028-0836. PMID 8990123.
  10. ^ Christendat, D.; Yee, A.; Dharamsi, A.; Kluger, Y.; Savchenko, A.; Cort, J. R.; Booth, V.; Mackereth, C. D.; Saridakis, V. (October 2000). "Structural proteomics of an archaeon". Nature Structural Biology. 7 (10): 903–909. doi:10.1038/82823. ISSN 1072-8368. PMID 11017201.
  11. ^ Vedadi, Masoud; Niesen, Frank H.; Allali-Hassani, Abdellah; Fedorov, Oleg Y.; Finerty, Patrick J.; Wasney, Gregory A.; Yeung, Ron; Arrowsmith, Cheryl; Ball, Linda J. (2006-10-24). "Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination". Proceedings of the National Academy of Sciences of the United States of America. 103 (43): 15835–15840. Bibcode:2006PNAS..10315835V. doi:10.1073/pnas.0605224103. ISSN 0027-8424. PMC 1595307. PMID 17035505.
  12. ^ Dong, Aiping; Xu, Xiaohui; Edwards, Aled M.; Midwest Center for Structural Genomics; Structural Genomics Consortium; Chang, Changsoo; Chruszcz, Maksymilian; Cuff, Marianne; Cymborowski, Marcin (December 2007). "In situ proteolysis for protein crystallization and structure determination". Nature Methods. 4 (12): 1019–1021. doi:10.1038/nmeth1118. ISSN 1548-7105. PMC 3366506. PMID 17982461.
  13. ^ Horner, Michael A.; Pardee, Keith; Liu, Suya; King-Jones, Kirst; Lajoie, Gilles; Edwards, Aled; Krause, Henry M.; Thummel, Carl S. (2009-12-01). "The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis". Genes & Development. 23 (23): 2711–2716. doi:10.1101/gad.1833609. ISSN 1549-5477. PMC 2788327. PMID 19952106.
  14. ^ Reinking, Jeff; Lam, Mandy M. S.; Pardee, Keith; Sampson, Heidi M.; Liu, Suya; Yang, Ping; Williams, Shawn; White, Wendy; Lajoie, Gilles (2005-07-29). "The Drosophila nuclear receptor e75 contains heme and is gas responsive". Cell. 122 (2): 195–207. doi:10.1016/j.cell.2005.07.005. ISSN 0092-8674. PMID 16051145.
  15. ^ Lunin, Vladimir V.; Dobrovetsky, Elena; Khutoreskaya, Galina; Zhang, Rongguang; Joachimiak, Andrzej; Doyle, Declan A.; Bochkarev, Alexey; Maguire, Michael E.; Edwards, Aled M. (2006-04-06). "Crystal structure of the CorA Mg2+ transporter". Nature. 440 (7085): 833–837. doi:10.1038/nature04642. ISSN 1476-4687. PMC 3836678. PMID 16598263.
  16. ^ "RCDS PDB Search".
  17. ^ Morgan, Maxwell Robert; Roberts, Owen Gwilym; Edwards, Aled Morgan (2018). "Ideation and implementation of an open science drug discovery business model - M4K Pharma". Wellcome Open Research. 3: 154. doi:10.12688/wellcomeopenres.14947.1. ISSN 2398-502X. PMC 6346698. PMID 30705971.
  18. ^ Jones, Molly Morgan; Castle-Clarke, Sophie; Brooker, Daniel; Nason, Edward; Huzair, Farah; Chataway, Joanna (2014-12-30). "The Structural Genomics Consortium: A Knowledge Platform for Drug Discovery: A Summary". Rand Health Quarterly. 4 (3): 19. ISSN 2162-8254. PMC 5396214. PMID 28560088.
  19. ^ "MNI Open Research: bringing a new level of transparency to neurological research". The Neuro. Retrieved 2019-07-12.
  20. ^ Edwards, Aled; Morgan, Max; Al Chawaf, Arij; Andrusiak, Kerry; Charney, Rachel; Cynader, Zarya; ElDessouki, Ahmed; Lee, Yunjeong; Moeser, Andrew (May 31, 2017). "A trust approach for sharing research reagents". Science Translational Medicine. 9 (392): eaai9055. doi:10.1126/scitranslmed.aai9055. ISSN 1946-6242. PMID 28566431.
  21. ^ "Aled Edwards". Ashoka | Everyone a Changemaker. Retrieved 2019-07-12.
  22. ^ Edwards, Aled M.; Isserlin, Ruth; Bader, Gary D.; Frye, Stephen V.; Willson, Timothy M.; Yu, Frank H. (2011-02-10). "Too many roads not taken". Nature. 470 (7333): 163–165. Bibcode:2011Natur.470..163E. doi:10.1038/470163a. ISSN 1476-4687. PMID 21307913.
  23. ^ "Illuminating the Druggable Genome | NIH Common Fund". commonfund.nih.gov. Retrieved 2019-07-12.
  24. ^ Zimmer, Carl (2018-09-18). "Why Your DNA Is Still Uncharted Territory". The New York Times. ISSN 0362-4331. Retrieved 2019-07-12.
  25. ^ Arrowsmith, Cheryl H.; Audia, James E.; Austin, Christopher; Baell, Jonathan; Bennett, Jonathan; Blagg, Julian; Bountra, Chas; Brennan, Paul E.; Brown, Peter J. (August 2015). "The promise and peril of chemical probes". Nature Chemical Biology. 11 (8): 536–541. doi:10.1038/nchembio.1867. ISSN 1552-4469. PMC 4706458. PMID 26196764.
  26. ^ General, Office of the Secretary to the Governor (2009-07-01). "Governor General announces 60 new appointments to the Order of Canada". The Governor General of Canada. Retrieved 2019-07-12.