Simon Boulton

Boulton studied Molecular Biology at the University of Edinburgh, then studied for a Ph.D. at the University of Cambridge under Professor Steve Jackson of the Gurdon Institute from 1994 to 1998.{{cite web|last=Boulton|first=Simon|title=Keynote Seminar "Biologie & Clinique"|url=http://www.institutpaolicalmettes.fr/uploads/tx_blragenda/Keynote20_04_12.pdf|publisher=Institut Paoli-Calmettes|access-date=24 May 2013}} It was at Cambridge that Boulton began researching mechanisms of DNA. He has described his first exposure to the research environment at Cambridge as "extremely influential."{{cite web|title=April 2011|url=http://maxreview.info/2011/04/page/3/|publisher=The Medical Blog|access-date=24 May 2013}}{{cite web| title =Keynote Speakers | work =institutpaolicalmettes| url =http://www.institutpaolicalmettes.fr/uploads/tx_blragenda/Keynote20_04_12.pdf}}{{cite web| title =EMBO gold medal 2011 awarded to Simon Boulton| work =EMBO| url =http://www.embo.org/news/press-releases-2011/embo-gold-medal-2011-awarded-to-simon-boulton.html }}

The website of Cancer Research UK explains Boulton's work in this way: human DNA "is constantly under assault from chemical reactions taking place in our bodies and from things we're exposed to in our everyday lives....Most of the time, DNA damage is repaired successfully by the cell. But if the cell continues to grow whilst its DNA is already damaged, it can lead to cancer." Boulton is learning about DNA damage repair "by first studying it inside a microscopic worm called C. elegans and then extending these findings to human cells," an approach that has revealed "remarkable similarities between the genes and proteins used to repair DNA damage in the worm and in humans....By studying this fundamental process of DNA damage repair, the researchers have contributed to our understanding of how faults in the system can lead to cancer."{{cite web| title =Understanding how cells repair DNA damage| work =Cancer Research UK| url =http://www.cancerresearchuk.org/cancer-info/cancerandresearch/ourcurrentresearch/researchbygrantee/dr-simon-boulton?ssSourceSiteId=funding}}

Boulton himself has explained his work at the DNA Damage Response Laboratory as follows: "DNA is a highly reactive molecule that is susceptible to damage. Fortunately, cells have evolved specialised repair processes that are remarkably efficient in correcting specific types of DNA damage. Failure to correctly repair DNA damage will lead to mutagenic change, which can contribute to ageing and cancer. Indeed, defects in genes that repair DNA damage are the underlying cause of a number of hereditary ageing/cancer predisposition syndromes such as Fanconi anemia and Blooms. The focus of my lab is to identify new DNA repair genes, understand how they work in DNA repair in mitotic and meiotic cells and determine how defects in these processes contribute to human disease such as cancer. We hope that our work will provide an improved understanding of how DNA repair works and how, when DNA repair is compromised, it contributes to cancer/ageing and or infertility disorders in humans."{{cite web| title =Simon Boulton : DNA Damage Response| work =London Research Institute| url =http://www.london-research-institute.org.uk/research/simon-boulton| url-status =dead| archive-url =https://web.archive.org/web/20140804134145/http://www.london-research-institute.org.uk/research/simon-boulton| archive-date =4 August 2014| df =dmy-all}} According to the Royal Society, Boulton's research has resulted in several major breakthroughs in understanding; these are viewed as highly promising with regard to the potential development of new cancer treatments.{{cite web| title =The Royal Society| work =Repairing the Code| url =http://royalsociety.org/events/2011/repairing-code/}}

File:DNA Repair.jpg

DNA is highly reactive and susceptible to damage from things we are exposed to in everyday life. Fortunately, DNA has evolved processes in which it has the ability to repair itself. If the damages are not repaired and it continues to grow, mutagenic changes occur causing ageing and cancer. Boulton is responsible for identifying these new DNA repair genes, understanding how these genes work in DNA, and determining how the defects in these processes contribute to human diseases.{{cite web|title=Simon Boulton|url=http://www.london-research-institute.org.uk/research/simon-boulton|publisher=London-Research Institute|archive-date=2014-08-04|archive-url=https://web.archive.org/web/20140804134145/http://www.london-research-institute.org.uk/research/simon-boulton}} To fulfil these tasks, Boulton studies the DNA damage repair inside a specific worm called C. elegans, then extends these findings to human cells. Through this process, he has found "remarkable similarities between the genes and proteins used to repair DNA damage in the worm and in humans....By studying this fundamental process of DNA damage repair, the researchers have contributed to our understanding of how faults in the system can lead to cancer."{{cite web|title=Simon Boulton|url=http://www.cancerresearchuk.org/cancer-info/cancerandresearch/ourcurrentresearch/researchbygrantee/dr-simon-boulton?ssSourceSiteId=funding|publisher=Cancer Research UK|access-date=24 May 2013}} Boulton's research has resulted in several major breakthroughs that are viewed as highly promising with regard to the potential development of new cancer treatments.{{cite web|title=Repairing the Code|url=http://royalsociety.org/events/2011/repairing-code/|publisher=The Royal Society|access-date=24 May 2013}}

Boulton's papers about his work have appeared in a number of major scientific journals, such as Nature,{{Cite journal | last1 = Boulton | first1 = S. J. | title = DNA repair: A heavyweight joins the fray | doi = 10.1038/462857a | journal = Nature | volume = 462 | issue = 7275 | pages = 857–858 | year = 2009 | pmid = 20016586| bibcode = 2009Natur.462..857B | s2cid = 4373844 | doi-access = free }}{{Cite journal | last1 = Boulton | first1 = S. J. | title = DNA repair: Decision at the break point | doi = 10.1038/465301a | journal = Nature | volume = 465 | issue = 7296 | pages = 301–302 | year = 2010 | pmid = 20485424 | bibcode = 2010Natur.465..301B | s2cid = 4387088 }} Science,{{Cite journal

| last1 = Ahel | first1 = D.

| last2 = Horejsí | first2 = Z.

| last3 = Wiechens | first3 = N.

| last4 = Polo | first4 = S. E.

| last5 = Garcia-Wilson | first5 = E.

| last6 = Ahel | first6 = I.

| last7 = Flynn | first7 = H.

| last8 = Skehel | first8 = M.

| last9 = West | first9 = S. C.

| last10 = Jackson

| doi = 10.1126/science.1177321 | first10 = S. P.

| last11 = Owen-Hughes | first11 = T.

| last12 = Boulton | first12 = S. J.

| title = Poly(ADP-ribose)-Dependent Regulation of DNA Repair by the Chromatin Remodeling Enzyme ALC1

| journal = Science

| volume = 325

| issue = 5945

| pages = 1240–1243

| year = 2009

| pmid = 19661379

| pmc =3443743

| bibcode = 2009Sci...325.1240A

}} Cell,{{Cite journal

| pmid = 22579284

| year = 2012

| last1 = Vannier

| first1 = J. B.

| title = RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity

| journal = Cell

| volume = 149

| issue = 4

| pages = 795–806

| last2 = Pavicic-Kaltenbrunner

| first2 = V

| last3 = Petalcorin

| first3 = M. I.

| last4 = Ding

| first4 = H

| last5 = Boulton

| first5 = S. J.

| doi = 10.1016/j.cell.2012.03.030

| doi-access = free

}}{{Cite journal

| pmid = 19804748

| year = 2009

| last1 = Boulton

| first1 = S. J.

| title = Condensin(g) crossover control to a few breaks

| journal = Cell

| volume = 139

| issue = 1

| pages = 21–3

| doi = 10.1016/j.cell.2009.09.016

| s2cid = 15262949

| doi-access = free

}}{{Cite journal

| pmid = 18957201

| pmc = 3726190

| year = 2008

| last1 = Barber

| first1 = L. J.

| title = RTEL1 maintains genomic stability by suppressing homologous recombination

| journal = Cell

| volume = 135

| issue = 2

| pages = 261–71

| last2 = Youds

| first2 = J. L.

| last3 = Ward

| first3 = J. D.

| last4 = McIlwraith

| first4 = M. J.

| last5 = O'Neil

| first5 = N. J.

| last6 = Petalcorin

| first6 = M. I.

| last7 = Martin

| first7 = J. S.

| last8 = Collis

| first8 = S. J.

| last9 = Cantor

| first9 = S. B.

| last10 = Auclair

| first10 = M

| last11 = Tissenbaum

| first11 = H

| last12 = West

| first12 = S. C.

| last13 = Rose

| first13 = A. M.

| last14 = Boulton

| first14 = S. J.

| doi = 10.1016/j.cell.2008.08.016

}} and Molecular Cell.{{Cite journal | last1 = Chapman | first1 = J. R. | last2 = Taylor | first2 = M. R. G. | last3 = Boulton | first3 = S. J. | doi = 10.1016/j.molcel.2012.07.029 | title = Playing the End Game: DNA Double-Strand Break Repair Pathway Choice | journal = Molecular Cell | volume = 47 | issue = 4 | pages = 497–510 | year = 2012 | pmid = 22920291| doi-access = free }}

After receiving his Ph.D. from Cambridge, Boulton completed postdoctoral fellowships funded by the European Molecular Biology Organization and the Human Frontier Science Program at Harvard Medical School. He first worked under Professor Nicholas Dyson of the Massachusetts General Hospital Cancer Center, then under Professor Marc Vidal of the Dana Faber Cancer Institute at Harvard Medical School. In 2002, Boulton joined Cancer Research UK, working at its London Research Institute, Clare Hall Laboratories, in South Mimms, and in Hertfordshire. He established his own research group there, and was eventually promoted to Senior Scientist in 2007.{{cite web|title=HFSP Alumni News: Simon Boulton awarded the 2011 Francis Crick Lecture|url=http://www.hfsp.org/about-us/press-and-media-centre/news-items/hfsp-alumni-news-simon-boulton-awarded-2011-francis-crick|publisher=Human Frontier Science Program|access-date=24 May 2013}}

He is a member of the Editorial Board for Genes & Development.{{Cite web|url=http://genesdev.cshlp.org/site/misc/edboard.xhtml|title = Genes & Development -- Genes & Development Editorial Board}}

Boulton’s PhD supervisor, Stephen P. Jackson, has said that it is Boulton's distinctive combination of approaches that has allowed Boulton to make seminal contributions to DNA repair, genome instability, and cancer. Among Boulton's achievements is the discovery that the gene RTEL1 serves as an anti-recombinase that affects genome stability and cancer and counteracts toxic recombination. In addition, he and his team discovered the PBZ motif and determined that ALC1 (Amplified in Liver Cancer 1) is a poly(ADP-ribose)-activated chromatin-remodelling enzyme required for DNA repair, and that poly (ADP-ribosyl)ation (PAR) is a post-translational modification of proteins that play an important role in mediating protein interactions and the recruitment of specific protein targets.

Also, he has discovered that the Fanconi Anemia proteins FANCM and FAAP24 are required for checkpoint-kinase signalling (ATR) in response to DNA damage and established that DNA repair defects of Fanconi Anemia cells can be suppressed by blocking non-homologous end joining. He has also demonstrated that a newly identified helicase, RTEL1, plays a crucial role in repairing double-stranded DNA breaks by means of homologous recombination (HR) – a discovery that has great therapeutic significance and that has already led to the development of treatments, with a drug currently undergoing clinical tests.{{cite web|title=Dr Simon Boulton receives the 2008 Eppendorf Young European Investigator Award|url=http://www.prohealthservicezone.com/News_Detail_Dr_simon_boulton_receives_the_2008_eppendorf_young_european_investigator_award__3499.asp#axzz2J7HNCTsE|publisher=Pro Health Service Zone|access-date=24 May 2013}}{{cite web| title =Dr Simon Boulton receives the 2008 Eppendorf Young European Investigator Award| work =Pro Health Service Zone| url =http://www.prohealthservicezone.com/News_Detail_Dr_simon_boulton_receives_the_2008_eppendorf_young_european_investigator_award__3499.asp#axzz2J7HNCTsE}}

The discoveries made in Boulton's laboratory have led to new therapeutic approaches. The findings about ALC1 may prove to have significant implications for the treatment of liver cancer. The discoveries about Fanconi Anemia proteins, moreover, suggest that NHEJ inhibitors might help suppress Fanconi Anemia patients' predisposition to cancer.

Boulton won the Colworth Medal{{Cite journal

| pmid = 17052168

| year = 2006

| last1 = Boulton

| first1 = S. J.

| title = Cellular functions of the BRCA tumour-suppressor proteins

| journal = Biochemical Society Transactions

| volume = 34

| issue = Pt 5

| pages = 633–45

| doi = 10.1042/BST0340633

}} from the Biochemical Society in 2006, and was selected to give the EACR Young Cancer Researcher of the Year award lecture in 2008. He was presented with the Eppendorf/Nature Young Investigator Award in 2008 for his research into DNA damage, specifically his work with RTEL1. He became a member of the European Molecular Biology Organization (EMBO) in 2009, and was awarded a Royal Society Wolfson Research Merit Award in 2010. He won the EMBO Gold Medal in 2011 for his research on DNA repair mechanisms. The election committee said that it was "particularly impressed by his pioneering role in establishing the nematode worm, C. elegans, as a model system to study genome instability." In 2011, Boulton was chosen to give the Royal Society Francis Crick Prize Lecture, an honour awarded annually by the Royal Society.{{cite web

| title =Repairing the code

| work =The Royal Society

| date =7 December 2011

| url =http://royalsociety.org/events/2011/repairing-code/

}} He was selected for this honour in recognition of his achievements in the field of DNA repair. Boulton was elected as a Fellow of the Academy of Medical Sciences in 2012.{{cite web

| title =Welcome to the Academy of Medical Sciences

| work =Academy of Medical Sciences

| url =http://www.acmedsci.ac.uk

}} In 2013, Boulton was the recipient of the Paul Marks Prize for Cancer Research, which recognises a new generation of leaders in cancer research who are making significant contributions to the understanding of cancer.{{cite web

| title =Paul Marks Prize for Cancer Research

| work =Memorial Sloan Kettering Cancer Center

| url =http://www.mskcc.org/research/paul-marks-prize-research

}}{{cite web

| title =Doing the twist on damaged DNA – Simon Boulton wins the Paul Marks cancer research prize

| work =Cancer Research UK

| date =23 September 2013

| url =http://scienceblog.cancerresearchuk.org/2013/09/23/doing-the-twist-and-damaged-dna-simon-boulton-wins-the-paul-marks-cancer-research-prize

}} He was elected a Fellow of the Royal Society in May 2022.{{Cite web |date=2022-05-10 |title=Outstanding scientists elected as Fellows and Foreign Members of the Royal Society |url=https://royalsociety.org/news/2022/05/new-fellows-2022/ |access-date=2022-05-11 |website=Royal Society}}

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Category:1972 births

Category:Members of the European Molecular Biology Organization

Category:Alumni of the University of Edinburgh

Category:Alumni of the University of Cambridge

Category:Academics of University College London

Category:Scientists from Leeds

Category:20th-century British biologists

Category:21st-century British biologists

Category:British geneticists

Category:British cancer researchers

Category:Living people

Category:Academics of the Francis Crick Institute

Category:Fellows of the Royal Society