Tomas Lindahl | |
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Born | Tomas Robert Lindahl 28 January 1938 [1] Stockholm, Sweden |
Nationality | Swedish, naturalised British (dual nationality) |
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Known for | Clarification of cellular resistance to carcinogens |
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Scientific career | |
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Thesis | On the structure and stability of nucleic acids in solution (1967) |
Website | crick |
Tomas Robert Lindahl FRS [3] FMedSci [5] (born 28 January 1938) is a Swedish-British scientist specialising in cancer research. [7] In 2015, he was awarded the Nobel Prize in Chemistry [8] jointly with American chemist Paul L. Modrich and Turkish chemist Aziz Sancar for mechanistic studies of DNA repair. [9] [10] [11]
Lindahl was born in Kungsholmen, Stockholm, Sweden to Folke Robert Lindahl and Ethel Hulda Hultberg. [12] He received a PhD degree in 1967, [13] and an MD degree qualification in 1970, from the Karolinska Institutet in Stockholm. [1]
After obtaining his research doctorate, Lindahl did postdoctoral research at Princeton University and Rockefeller University. [14] He was professor of medical chemistry at the University of Gothenburg 1978–82. After moving to the United Kingdom he joined the Imperial Cancer Research Fund (now Cancer Research UK) as a researcher in 1981. [14] From 1986 to 2005 he was the first Director of Cancer Research UK's Clare Hall Laboratories in Hertfordshire, since 2015 part of the Francis Crick Institute. [15] He continued to research there until 2009. He has contributed to many papers on DNA repair and the genetics of cancer. [16] [17] [18] [19] [20] [21] [22] [23] [24]
Lindahl was elected an EMBO Member in 1974 [2] and Fellow of the Royal Society (FRS) in 1988, [4] his certificate of election reads:
Dr. Tomas Lindahl is noted for his contributions to the comprehension of DNA repair at the molecular level in bacterial and mammalian cells. He was the first to isolate a mammalian DNA ligase and to describe a totally unanticipated novel group of DNA glycosylases as mediators of DNA excision repair. He has also discovered a unique class of enzymes in mammalian cells, namely the methyltransferases, which mediate the adaptive response to alkylation of DNA and has shown that the expression of these enzymes is regulated by the ada gene. More recently he has elucidated the molecular defect in Blooms syndrome [ sic ] to be the lack of DNA ligase I. Apart from providing profound insights into the nature of the DNA repair process his very important contributions promise to facilitate the design of more selective chemotherapeutic drugs for the treatment of cancer. Lindahl has also made a number of significant contributions to understanding at the DNA level the mechanism of transformation of B-lymphocytes by the Epstein-Barr virus. The most notable of these was the first description of the occurrence in lymphoid cells of closed circular duplex viral DNA. [3]
Lindahl received the Royal Society's Royal Medal in 2007 "making fundamental contributions to our understanding of DNA repair. His achievements stand out for their great originality, breadth and lasting influence." [25] He is a member of the Norwegian Academy of Science and Letters. [26] He was awarded the Copley Medal in 2010. He was elected a founding Fellow of the Academy of Medical Sciences (FMedSci) in 1998. In 2018, he was elected a foreign associate of the National Academy of Sciences.
He shared the Nobel Prize in Chemistry in 2015. [9] The Swedish Academy noted that "The Nobel Prize in Chemistry 2015 was awarded jointly to Tomas Lindahl, Paul Modrich and Aziz Sancar 'for mechanistic studies of DNA repair'." [27]
Cancer Research UK (CRUK) is the world's largest independent cancer research organisation. It is registered as a charity in the United Kingdom and Isle of Man, and was formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Cancer Research UK conducts research using both its own staff and grant-funded researchers. It also provides information about cancer and runs campaigns aimed at raising awareness and influencing public policy.
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur. This can eventually lead to malignant tumors, or cancer as per the two-hit hypothesis.
Sir John Bertrand Gurdon is a British developmental biologist, best known for his pioneering research in nuclear transplantation and cloning.
Sir Martin John EvansFLSW is an English biologist who, with Matthew Kaufman, was the first to culture mice embryonic stem cells and cultivate them in a laboratory in 1981. He is also known, along with Mario Capecchi and Oliver Smithies, for his work in the development of the knockout mouse and the related technology of gene targeting, a method of using embryonic stem cells to create specific gene modifications in mice. In 2007, the three shared the Nobel Prize in Physiology or Medicine in recognition of their discovery and contribution to the efforts to develop new treatments for illnesses in humans.
Michael Samuel Neuberger FRS FMedSci was a British biochemist and immunologist.
Aziz Sancar is a Turkish molecular biologist specializing in DNA repair, cell cycle checkpoints, and circadian clock. In 2015, he was awarded the Nobel Prize in Chemistry along with Tomas Lindahl and Paul L. Modrich for their mechanistic studies of DNA repair. He has made contributions on photolyase and nucleotide excision repair in bacteria that have changed his field.
The Cancer Research UK London Research Institute (LRI) was a biological research facility which conducted research into the basic biology of cancer.
Richard D. Wood is an American molecular biologist specializing in research on DNA repair and mutation. He is known for pioneering studies on nucleotide excision repair (NER), particularly for reconstituting the minimum set of proteins involved in this process, identifying proliferating cell nuclear antigen (PCNA) as part of the NER complex and identifying mammalian repair polymerases.
Transcription factor II H (TFIIH) is an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair (NER) pathways. TFIIH first came to light in 1989 when general transcription factor-δ or basic transcription factor 2 was characterized as an indispensable transcription factor in vitro. This factor was also isolated from yeast and finally named TFIIH in 1992.
Paul Lawrence Modrich is an American biochemist, James B. Duke Professor of Biochemistry at Duke University and Investigator at the Howard Hughes Medical Institute. He is known for his research on DNA mismatch repair. Modrich received the Nobel Prize in Chemistry 2015, jointly with Aziz Sancar and Tomas Lindahl.
DNA ligase 1 also DNA ligase I, is an enzyme that in humans is encoded by the LIG1 gene. DNA ligase 1 is the only known eukaryotic DNA ligase involved in both DNA replication and repair, making it the most studied of the ligases.
Single-strand selective monofunctional uracil DNA glycosylase is an enzyme that in humans is encoded by the SMUG1 gene. SMUG1 is a glycosylase that removes uracil from single- and double-stranded DNA in nuclear chromatin, thus contributing to base excision repair.
Sir Adrian Peter Bird, is a British geneticist and Buchanan Professor of Genetics at the University of Edinburgh. Bird has spent much of his academic career in Edinburgh, from receiving his PhD in 1970 to working at the MRC Mammalian Genome Unit and later serving as director of the Wellcome Trust Centre for Cell Biology. His research focuses on understanding DNA methylation and CpG islands, and their role in diseases such as Rett syndrome.
Laurence Harris Pearl FRS FMedSci is a British biochemist and structural biologist who is currently Professor of Structural Biology in the Genome Damage and Stability Centre and was Head of the School of Life Sciences at the University of Sussex.
George Gow Brownlee FRS FMedSci is a British pathologist and Fellow of Lincoln College, Oxford.
Sir Shankar Balasubramanian is an Indian-born British chemist and Herchel Smith Professor of Medicinal Chemistry in the Department of Chemistry at the University of Cambridge, Senior Group Leader at the Cancer Research UK Cambridge Institute and Fellow of Trinity College, Cambridge. He is recognised for his contributions in the field of nucleic acids. He is scientific founder of Solexa and biomodal.
Sir Stephen Philip Jackson, FRS, FMedSci is the Frederick James Quick Professor of Biology. He is a senior group leader at the Cancer Research UK Cambridge Institute and associate group leader at the Gurdon Institute, University of Cambridge.
Patrik Rorsman FRS FMedSci is Professor of Diabetic Medicine at the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), in the Radcliffe Department of Medicine at the University of Oxford and a fellow of Harris Manchester College, Oxford.
Ketan Jayakrishna Patel is a British–Kenyan scientist who is Director of the MRC Weatherall Institute of Molecular Medicine and the MRC Molecular Haematology Unit at the University of Oxford. Until 2020 he was a tenured principal investigator at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB).
Sir David Klenerman is a British biophysical chemist and a professor of biophysical chemistry at the Department of Chemistry at the University of Cambridge and a Fellow of Christ's College, Cambridge.
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