Simon Boulton
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Simon Joseph Boulton is a British scientist who has made important contributions to the understanding of DNA repair and the treatment of
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
resulting from DNA damage. He currently occupies the position of Senior Scientist and group leader of the DSB Repair Metabolism Laboratory at the Francis Crick Institute, London. He is also an honorary Professor at
University College London , mottoeng = Let all come who by merit deserve the most reward , established = , type = Public research university , endowment = £143 million (2020) , budget = ...
.


Early life and education

Boulton studied Molecular Biology at the
University of Edinburgh The University of Edinburgh ( sco, University o Edinburgh, gd, Oilthigh Dhùn Èideann; abbreviated as ''Edin.'' in post-nominals) is a public research university based in Edinburgh, Scotland. Granted a royal charter by King James VI in 15 ...
, then studied for a Ph.D. at the
University of Cambridge , mottoeng = Literal: From here, light and sacred draughts. Non literal: From this place, we gain enlightenment and precious knowledge. , established = , other_name = The Chancellor, Masters and Schola ...
under Professor Steve Jackson of the
Gurdon Institute The Gurdon Institute (officially the Wellcome/Cancer Research UK Gurdon Institute) is a research facility at the University of Cambridge, specialising in developmental biology and cancer biology. History The Institute was founded in 1989 to prov ...
from 1994 to 1998. 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."


Research

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." 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." Boulton's research has resulted in several major breakthroughs in understanding that are viewed as highly promising with regard to the potential development of new cancer treatments.


DNA Damage Response Laboratory

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. 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." 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. Boulton's papers about his work have appeared in a number of major scientific journals, such as ''
Nature Nature, in the broadest sense, is the physics, physical world or universe. "Nature" can refer to the phenomenon, phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. ...
'', ''
Science Science is a systematic endeavor that builds and organizes knowledge in the form of testable explanations and predictions about the universe. Science may be as old as the human species, and some of the earliest archeological evidence for ...
'', '' Cell'', and ''
Molecular Cell ''Molecular Cell'' is a peer-reviewed scientific journal that covers research on cell biology at the molecular level, with an emphasis on new mechanistic insights. It was established in 1997 and is published two times per month. Its 2021 impact ...
''.


Career

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 Nicholas Dyson is Professor of Medicine at Harvard Medical School, the James and Shirley Curvey MGH Research Scholar and Scientific Director of the Massachusetts General Hospital Cancer Center. Research The Dyson Lab studies the retinoblastoma ...
of the
Massachusetts General Hospital Massachusetts General Hospital (Mass General or MGH) is the original and largest teaching hospital of Harvard Medical School located in the West End neighborhood of Boston, Massachusetts. It is the third oldest general hospital in the United Stat ...
Cancer Center, then under Professor Marc Vidal of the Dana Faber Cancer Institute at
Harvard Medical School Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
. In 2002, Boulton joined Cancer Research UK, working at its London Research Institute, Clare Hall Laboratories, in South Mimms, and in
Hertfordshire Hertfordshire ( or ; often abbreviated Herts) is one of the home counties in southern England. It borders Bedfordshire and Cambridgeshire to the north, Essex to the east, Greater London to the south, and Buckinghamshire to the west. For govern ...
. He established his own research group there, and was eventually promoted to Senior Scientist in 2007. He is a member of the Editorial Board for '' Genes & Development''. 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. 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.


Honours and awards

Boulton won the Colworth Medal from the
Biochemical Society The Biochemical Society is a learned society in the United Kingdom in the field of biochemistry, including all the cellular and molecular biosciences. Structure It currently has around 7000 members, two-thirds in the UK. It is affiliated with th ...
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 The EMBO Gold Medal is an annual award of the European Molecular Biology Organization (EMBO) given to young scientists for outstanding contributions to the life sciences in Europe. Laureates receive a medal and €10,000 and are invited to rec ...
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. 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. In 2013, Boulton was the recipient of the
Paul Marks Prize for Cancer Research The Paul Marks Prize for Cancer Research is awarded by the Memorial Sloan Kettering Cancer Center to recognize cancer researchers who are making significant contributions to the understanding of cancer or are improving the treatment of the disease t ...
, which recognises a new generation of leaders in cancer research who are making significant contributions to the understanding of cancer. He was elected a
Fellow of the Royal Society Fellowship of the Royal Society (FRS, ForMemRS and HonFRS) is an award granted by the judges of the Royal Society of London to individuals who have made a "substantial contribution to the improvement of natural science, natural knowledge, incl ...
in May 2022.


References

{{DEFAULTSORT:Boulton, Simon 1972 births Members of the European Molecular Biology Organization Alumni of the University of Edinburgh Alumni of the University of Cambridge Academics of University College London People from Leeds 20th-century British biologists 21st-century British biologists British geneticists British medical researchers Cancer researchers Living people Academics of the Francis Crick Institute Scientists from Yorkshire Fellows of the Royal Society