Adrian Bird

Last updated

Sir Adrian Bird
CBE FRS FRSE FMedSci
Adrian Bird.jpg
Born
Adrian Peter Bird

(1947-07-03) 3 July 1947 (age 77) [1]
Rowley Regis, Staffordshire, England [2]
Alma mater
Spouse
​
​
(m. 1993)​
[1]
Awards
Scientific career
Fields
Institutions
Thesis The cytology and biochemistry of DNA amplification in the ovary of Xenopus laevis  (1972)
Doctoral advisor Max Birnstiel [13] [14] [15]
Doctoral students Rob Klose [16]
Website birdlab.bio.ed.ac.uk

Sir Adrian Peter Bird (born 3 July 1947) 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. [17]

Contents

Education and early life

Bird was born in Rowley Regis near Wolverhampton, England, but from age 4 lived in the town of Kidderminster, near Birmingham. [18] He attended a grammar school in Hartlebury, achieving grades CCD for his A-level results. Whilst at school, Bird played cricket and hockey for a local team. [18] Bird received his PhD [13] from the University of Edinburgh in 1970 for research supervised by Max Birnstiel, [13] following undergraduate study of Biochemistry at the University of Sussex. [12]

Career and research

Following his PhD, Bird went on to postdoctoral research positions, first at Yale University with Joseph G. Gall, and then at the University of Zurich before returning to Edinburgh in 1975 to work at the MRC Mammalian Genome Unit, where he would stay for 11 years. [19] [20] It was here that Bird, along with Edwin Southern, mapped the methylation status of CpG dinucleotides along ribosomal RNA in the African clawed frog. [19] [21] From 1987 to 1990 Bird continued his research at the Research Institute of Molecular Pathology in Vienna.

In 1990, Adrian Bird became Buchanan Professor of Genetics at the University of Edinburgh. He helped create the Wellcome Trust Centre for Cell Biology, also in Edinburgh, and served as its director from 1999 until 2011, when he was succeeded by David Tollervey. [22] From 2000 to 2010, he was also a governor of the Wellcome Trust, serving as deputy chairman during the latter three years. [22] [23]

Bird is a trustee of the charitable organisation Cancer Research UK and of the Rett Syndrome Research Trust. [22] [24] He also serves as a Governance Board Member of the Edinburgh Cancer Research Centre. [25]

Bird's research has focused on CpG islands and their associated binding-factor MeCP2. [26] He led the team which first identified CpG islands—originally named "HpaII tiny fragments" [19] —in vertebrate genomes. These are short genomic regions with a high density of CpG dinucleotides, and are commonly found in an unmethylated state within or nearby to an active gene's promoter.

Bird's group discovered that the MeCP2 protein binds specifically to methylated CpG sites, and further that disruption of this interaction causes the autism spectrum disorder Rett syndrome. The Bird lab also implicated nuclear receptor co-repressor 1 as an important binding partner in the MeCP2/methyl-CpG interaction. [26]

In 2007, the Bird laboratory published a paper in the journal Science [27] describing a proof-of-principle that the murine equivalent of Rett syndrome could be successfully reversed in laboratory mice. [28] This was accomplished by reintroducing a functional MeCP2 gene and proved successful even when the condition was at an advanced stage, hinting at the possibility of a gene therapy approach to curing the human disease in the future. [28] [29]

Awards and honours

Bird was elected a Fellow of the Royal Society (FRS) in 1989, his nomination read:

Adrian Bird is the leading authority on DNA methylation in animal cells. He demonstrated a rolling circle mechanism for ribosomal gene amplification. He showed that DNA methylation sites can be mapped using restriction enzymes and thus showed semi-conservative copying of methylation patterns. He showed convincingly that the doublet CpG is a source of mutation in vertebrates which led to the use of 'GpG' restriction enzymes to detect polymorphisms linked to genetic diseases. He discovered unmethylated 'HTF' islands at the 5i ends of housekeeping genes. This discovery has allowed new strategies for mapping and identifying genes and it has allowed Bird to propose that the unmethylated HTF islands identify DNA sequences to be kept constantly available within the nucleus. [30]

Bird was awarded the Gabor Medal in 1999 "in recognition of his pioneering work in the study of global mechanisms by which transcription of the mammalian genome is regulated and for his exploration into the molecular basis of fundamental biological mechanisms, particularly his development of ways of analysing methylation patterns of eukaryotic DNA using endonucleases and the discovery of and continued research into a new class of DNA sequences found in all vertebrates". [31] He received the Louis-Jeantet Prize for Medicine in the same year, [23] and was made a Commander of the Order of the British Empire in the Queen's Birthday Honours in 2005.

In 2011, he was a recipient of the Gairdner Foundation International Award, "for his pioneering discoveries on DNA methylation and its role in gene expression." [32] The following year Bird won the 2012 GlaxoSmithKline Prize. [22] In 2013, he was named a Thomson Reuters Citation Laureate and received the 2013 BBVA Foundation Frontiers of Knowledge Award in Biomedicine "for his discoveries in the field of epigenetics". [20] [33]

In 2013, Bird was tipped as a potential winner of the Nobel Prize in Physiology or Medicine for "fundamental discoveries concerning DNA methylation and gene expression" [34] though the prize later went to James Rothman, Randy Schekman and Thomas C. Südhof.

He was knighted in the 2014 New Year Honours for services to science. [35] [36] [37]

In 2016, he was elected as a foreign associate of the National Academy of Sciences [38] and received the Shaw Prize together with Huda Y. Zoghbi. [39] In 2017 he received the Charles Rudolphe Brupbacher Prize. [40]

He was awarded the Buchanan Medal of the Royal Society in 2018 for his medical discoveries, [41] and elected a Fellow of the Academy of Medical Sciences (FMedSci) in 2001. [42] In 2020 he was awarded the Brain Prize. [43]

Personal life

Adrian Bird is married to fellow geneticist Cathy Abbott and has four children. [18] [19] At age 66, Bird was quoted as having no plans to retire, saying "we [the research group] are still funded well and our work is still published in journals and as long as that continues, so will I." [18]

Related Research Articles

<span class="mw-page-title-main">Epigenetics</span> Study of DNA modifications that do not change its sequence

In biology, epigenetics is the study of heritable traits, or a stable change of cell function, that happen without changes to the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic mechanism of inheritance. Epigenetics usually involves a change that is not erased by cell division, and affects the regulation of gene expression. Such effects on cellular and physiological phenotypic traits may result from environmental factors, or be part of normal development. Epigenetic factors can also lead to cancer.

<span class="mw-page-title-main">Rett syndrome</span> Genetic brain disorder

Rett syndrome (RTT) is a genetic disorder that typically becomes apparent after 6-18 months of age and almost exclusively in girls. Symptoms include impairments in language and coordination, and repetitive movements. Those affected often have slower growth, difficulty walking, and a smaller head size. Complications of Rett syndrome can include seizures, scoliosis, and sleeping problems. The severity of the condition is variable.

<span class="mw-page-title-main">5-Methylcytosine</span> Chemical compound which is a modified DNA base

5-Methylcytosine is a methylated form of the DNA base cytosine (C) that regulates gene transcription and takes several other biological roles. When cytosine is methylated, the DNA maintains the same sequence, but the expression of methylated genes can be altered. 5-Methylcytosine is incorporated in the nucleoside 5-methylcytidine.

<span class="mw-page-title-main">CpG site</span> Region of often-methylated DNA with a cytosine followed by a guanine

The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. CpG sites occur with high frequency in genomic regions called CpG islands.

A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and viruses.

<span class="mw-page-title-main">Regulation of gene expression</span> Modifying mechanisms used by cells to increase or decrease the production of specific gene products

Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products. Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.

<span class="mw-page-title-main">DNA methylation</span> Biological process

DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. In mammals, DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis.

<span class="mw-page-title-main">Epigenome</span> Biological term

In biology, the epigenome of an organism is the collection of chemical changes to its DNA and histone proteins that affects when, where, and how the DNA is expressed; these changes can be passed down to an organism's offspring via transgenerational epigenetic inheritance. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome. The human epigenome, including DNA methylation and histone modification, is maintained through cell division. The epigenome is essential for normal development and cellular differentiation, enabling cells with the same genetic code to perform different functions. The human epigenome is dynamic and can be influenced by environmental factors such as diet, stress, and toxins.

<span class="mw-page-title-main">MECP2</span> DNA-binding protein involved in methylation

MECP2 is a gene that encodes the protein MECP2. MECP2 appears to be essential for the normal function of nerve cells. The protein seems to be particularly important for mature nerve cells, where it is present in high levels. The MECP2 protein is likely to be involved in turning off several other genes. This prevents the genes from making proteins when they are not needed. Recent work has shown that MECP2 can also activate other genes. The MECP2 gene is located on the long (q) arm of the X chromosome in band 28 ("Xq28"), from base pair 152,808,110 to base pair 152,878,611.

<span class="mw-page-title-main">Methylation specific oligonucleotide microarray</span> Technique used to map epigenetic methylations in cancer DNA

Methylation specific oligonucleotide microarray, also known as MSO microarray, was developed as a technique to map epigenetic methylation changes in DNA of cancer cells.

<span class="mw-page-title-main">DNA (cytosine-5)-methyltransferase 3A</span> Protein-coding gene in the species Homo sapiens

DNA (cytosine-5)-methyltransferase 3A (DNMT3A) is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. The enzyme is encoded in humans by the DNMT3A gene.

Methylated DNA immunoprecipitation is a large-scale purification technique in molecular biology that is used to enrich for methylated DNA sequences. It consists of isolating methylated DNA fragments via an antibody raised against 5-methylcytosine (5mC). This technique was first described by Weber M. et al. in 2005 and has helped pave the way for viable methylome-level assessment efforts, as the purified fraction of methylated DNA can be input to high-throughput DNA detection methods such as high-resolution DNA microarrays (MeDIP-chip) or next-generation sequencing (MeDIP-seq). Nonetheless, understanding of the methylome remains rudimentary; its study is complicated by the fact that, like other epigenetic properties, patterns vary from cell-type to cell-type.

<span class="mw-page-title-main">Combined bisulfite restriction analysis</span>

Combined Bisulfite Restriction Analysis is a molecular biology technique that allows for the sensitive quantification of DNA methylation levels at a specific genomic locus on a DNA sequence in a small sample of genomic DNA. The technique is a variation of bisulfite sequencing, and combines bisulfite conversion based polymerase chain reaction with restriction digestion. Originally developed to reliably handle minute amounts of genomic DNA from microdissected paraffin-embedded tissue samples, the technique has since seen widespread usage in cancer research and epigenetics studies.

<span class="mw-page-title-main">Cancer epigenetics</span> Field of study in cancer research

Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed. Epigenetic mechanisms are necessary to maintain normal sequences of tissue specific gene expression and are crucial for normal development. They may be just as important, if not even more important, than genetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss of expression of genes that occurs about 10 times more frequently by transcription silencing than by mutations. As Vogelstein et al. points out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylated CpG islands in the promoters of genes in the tumors while these CpG islands are not methylated in the adjacent mucosa. Manipulation of epigenetic alterations holds great promise for cancer prevention, detection, and therapy. In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as the silencing of tumor suppressor genes and activation of oncogenes by altered CpG island methylation patterns, histone modifications, and dysregulation of DNA binding proteins. There are several medications which have epigenetic impact, that are now used in a number of these diseases.

Autism spectrum disorder (ASD) refers to a variety of conditions typically identified by challenges with social skills, communication, speech, and repetitive sensory-motor behaviors. The 11th International Classification of Diseases (ICD-11), released in January 2021, characterizes ASD by the associated deficits in the ability to initiate and sustain two-way social communication and restricted or repetitive behavior unusual for the individual's age or situation. Although linked with early childhood, the symptoms can appear later as well. Symptoms can be detected before the age of two and experienced practitioners can give a reliable diagnosis by that age. However, official diagnosis may not occur until much older, even well into adulthood. There is a large degree of variation in how much support a person with ASD needs in day-to-day life. This can be classified by a further diagnosis of ASD level 1, level 2, or level 3. Of these, ASD level 3 describes people requiring very substantial support and who experience more severe symptoms. ASD-related deficits in nonverbal and verbal social skills can result in impediments in personal, family, social, educational, and occupational situations. This disorder tends to have a strong correlation with genetics along with other factors. More research is identifying ways in which epigenetics is linked to autism. Epigenetics generally refers to the ways in which chromatin structure is altered to affect gene expression. Mechanisms such as cytosine regulation and post-translational modifications of histones. Of the 215 genes contributing, to some extent in ASD, 42 have been found to be involved in epigenetic modification of gene expression. Some examples of ASD signs are specific or repeated behaviors, enhanced sensitivity to materials, being upset by changes in routine, appearing to show reduced interest in others, avoiding eye contact and limitations in social situations, as well as verbal communication. When social interaction becomes more important, some whose condition might have been overlooked suffer social and other exclusion and are more likely to have coexisting mental and physical conditions. Long-term problems include difficulties in daily living such as managing schedules, hypersensitivities, initiating and sustaining relationships, and maintaining jobs.

Differentially methylated regions (DMRs) are genomic regions with different DNA methylation status across different biological samples and regarded as possible functional regions involved in gene transcriptional regulation. The biological samples can be different cells/tissues within the same individual, the same cell/tissue at different times, cells/tissues from different individuals, even different alleles in the same cell.

Epigenetics of depression is the study of how epigenetics contribute to depression.

<span class="mw-page-title-main">Robin Allshire</span> British academic

Robin Campbell Allshire is a British academic who is Professor of Chromosome Biology at University of Edinburgh and a Wellcome Trust Principal Research Fellow. His research group at the Wellcome Trust Centre for Cell Biology focuses on the epigenetic mechanisms governing the assembly of specialised domains of chromatin and their transmission through cell division.

CpG island hypermethylation is a phenomenon that is important for the regulation of gene expression in cancer cells, as an epigenetic control aberration responsible for gene inactivation. Hypermethylation of CpG islands has been described in almost every type of tumor.

<span class="mw-page-title-main">Rob Klose</span> Canadian geneticist

Rob Klose is a Canadian researcher and Professor of Genetics at the Department of Biochemistry, University of Oxford. His research investigates how chromatin-based and epigenetic mechanisms contribute to the ways in which gene expression is regulated.

References

  1. 1 2 Anon (2015). "Bird, Sir Adrian Peter" . Who's Who (online Oxford University Press  ed.). A & C Black. doi:10.1093/ww/9780199540884.013.U7581.(Subscription or UK public library membership required.)
  2. ↑ England & Wales, Civil Registration Birth Index, 1916-2007
  3. ↑ Prize
  4. ↑ Jaenisch, R.; Bird, A. (2003). "Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals". Nature Genetics . 33 Suppl (3s): 245–254. doi:10.1038/ng1089. PMID   12610534. S2CID   17270515.
  5. ↑ Bird, A (2007). "Perceptions of epigenetics". Nature. 447 (7143): 396–8. Bibcode:2007Natur.447..396B. doi: 10.1038/nature05913 . PMID   17522671. S2CID   4357965.
  6. ↑ Bird, A. P. (1986). "CpG-rich islands and the function of DNA methylation". Nature. 321 (6067): 209–13. Bibcode:1986Natur.321..209B. doi:10.1038/321209a0. PMID   2423876. S2CID   4236677.
  7. ↑ Bird, A (2002). "DNA methylation patterns and epigenetic memory". Genes & Development . 16 (1): 6–21. doi: 10.1101/gad.947102 . PMID   11782440.
  8. ↑ Bird, A. P.; Wolffe, A. P. (1999). "Methylation-induced repression--belts, braces, and chromatin". Cell. 99 (5): 451–4. doi: 10.1016/s0092-8674(00)81532-9 . PMID   10589672. S2CID   15201044.
  9. ↑ Lewis, J. D.; Meehan, R. R.; Henzel, W. J.; Maurer-Fogy, I; Jeppesen, P; Klein, F; Bird, A (1992). "Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA". Cell . 69 (6): 905–14. doi:10.1016/0092-8674(92)90610-O. PMID   1606614. S2CID   6825994.
  10. ↑ Nan, X; Ng, H. H.; Johnson, C. A.; Laherty, C. D.; Turner, B. M.; Eisenman, R. N.; Bird, A (1998). "Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex". Nature. 393 (6683): 386–9. Bibcode:1998Natur.393..386N. doi:10.1038/30764. PMID   9620804. S2CID   4427745.
  11. ↑ Cheval, H; Guy, J; Merusi, C; De Sousa, D; Selfridge, J; Bird, A (2012). "Postnatal inactivation reveals enhanced requirement for MeCP2 at distinct age windows". Human Molecular Genetics . 21 (17): 3806–14. doi:10.1093/hmg/dds208. PMC   3412380 . PMID   22653753. Open Access logo PLoS transparent.svg
  12. 1 2 "Professor Adrian Bird – Associate Faculty". Wellcome Trust Sanger Institute. Archived from the original on 7 April 2015.
  13. 1 2 3 Bird, Adrian (1972). The cytology and biochemistry of DNA amplification in the ovary of Xenopus laevis (Thesis). University of Edinburgh. hdl:1842/11977. EThOS   uk.bl.ethos.641632. Open Access logo PLoS transparent.svg
  14. ↑ Bird, A. (2007). "Q&A: Adrian Bird". Current Biology . 17 (11): R393–R394. Bibcode:2007CBio...17.R393B. doi: 10.1016/j.cub.2007.03.018 . PMID   17600901. S2CID   13050386.
  15. ↑ Schatz, G. (2015). "Max L. Birnstiel (1933–2014)". Cell. 160 (1–2): 11–12. doi: 10.1016/j.cell.2014.12.030 .
  16. ↑ Klose, Rob (2005). Biochemical analysis of MeCP2 (PhD thesis). University of Edinburgh. hdl:1842/10997. EThOS   uk.bl.ethos.653493. Open Access logo PLoS transparent.svg
  17. ↑ Adrian Bird's publications indexed by the Scopus bibliographic database. (subscription required)
  18. 1 2 3 4 Tomaney, William (9 January 2014). "Geneticist raised in Kidderminster happy with knighthood". The Shuttle. Newsquest. Archived from the original on 2 February 2014.
  19. 1 2 3 4 Bird, A (2009). "On the track of DNA methylation: An interview with Adrian Bird by Jane Gitschier". PLOS Genetics. 5 (10): e1000667. doi: 10.1371/journal.pgen.1000667 . PMC   2753650 . PMID   19834538.
  20. 1 2 "BBVA Foundation Frontiers of Knowledge Awards: Biomedicine 2013". BBVA Foundation. Archived from the original on 3 February 2014. Retrieved 31 January 2014.
  21. ↑ Bird, A. P.; Southern, E. M. (1978). "Use of restriction enzymes to study eukaryotic DNA methylation: I. The methylation pattern in ribosomal DNA from Xenopus laevis". Journal of Molecular Biology . 118 (1): 27–47. doi:10.1016/0022-2836(78)90242-5. PMID   625056.
  22. 1 2 3 4 School of Biology Sciences (7 January 2014). "Knighthood for Adrian Bird". University of Edinburgh . Retrieved 18 January 2014.
  23. 1 2 "Elite award for Adrian Bird, Buchanan Professor of Genetics at The University of Edinburgh". Edinburgh Science Triangle. 30 March 2011. Archived from the original on 7 January 2014. Retrieved 6 January 2014.
  24. ↑ "Elite award for Adrian Bird". University of Edinburgh. 11 May 2011. Archived from the original on 7 January 2014. Retrieved 6 January 2014.
  25. ↑ Governance Board Members of the Edinburgh Cancer Research Centre. Archived 7 January 2014 at the Wayback Machine Retrieved 7 January 2014.
  26. 1 2 "Adrian Bird". Wellcome Trust Centre for Cell Biology. Retrieved 6 January 2014.
  27. ↑ Guy, J; Gan, J; Selfridge, J; Cobb, S; Bird, A (2007). "Reversal of neurological defects in a mouse model of Rett syndrome". Science. 315 (5815): 1143–7. Bibcode:2007Sci...315.1143G. doi:10.1126/science.1138389. PMC   7610836 . PMID   17289941. S2CID   25172134.
  28. 1 2 "Professor Bird knighted in New Year's Honours List". Reverse Rett. Archived from the original on 6 January 2014. Retrieved 6 January 2014.
  29. ↑ McLaren, C. (2010). "Adrian Bird lab: Our research". University of Edinburgh. Retrieved 6 January 2014.
  30. ↑ "EC/1989/04: Bird, Adrian Peter". London: The Royal Society. Archived from the original on 4 July 2019. Retrieved 22 April 2015.
  31. ↑ "Gabor previous winners 2005–1989". The Royal Society. Archived from the original on 11 March 2008. Retrieved 5 February 2009.
  32. ↑ "Gairdner Awards – Adrian Peter Bird, PhD". Archived from the original on 17 October 2013.
  33. ↑ "European award for celebrated scientist". The University of Edinburgh. Retrieved 29 January 2014.
  34. ↑ Gray, Richard (23 September 2013). "Higgs Boson scientist tipped to win Nobel Prize". The Telegraph. Archived from the original on 25 September 2013. Retrieved 30 December 2013.
  35. ↑ "No. 60728". The London Gazette (Supplement). 31 December 2013. p. 1.
  36. ↑ "Met Office chief scientist becomes Dame in honours list". BBC News. 30 December 2013. Retrieved 30 December 2013.
  37. ↑ "The New Year's Honours 2014". Cabinet Office. Gov.uk. 30 December 2013. Retrieved 30 December 2013.
  38. ↑ National Academy of Sciences Members and Foreign Associates Elected, News from the National Academy of Sciences, National Academy of Sciences, 3 May 2016, retrieved 14 May 2016.
  39. ↑ "Shaw Prize 2016". Archived from the original on 4 June 2016. Retrieved 31 May 2016.
  40. ↑ "Charles Rodolphe Brupbacher Prize". Charles Rodolphe Brupbacher Foundation. 2017. Archived from the original on 22 December 2017. Retrieved 20 December 2017.
  41. ↑ "Buchanan Medal". Royal Society. Retrieved 6 September 2018.
  42. ↑ "Professor Sir Adrian Bird CBE FRS FRSE FMedSci". Archived from the original on 22 April 2015.
  43. ↑ "Prize Winners 2020". The Lundbeck Foundation. Archived from the original on 13 May 2020. Retrieved 29 April 2020.
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