Ruth Clayton (née Freedman;10 June 1925 – 2003) was a lecturer and researcher with an international reputation in eye research at the University of Edinburgh in the Institute of Animal Genetics.Truman, DES. Obituaries: Ruth Clayton. Bulletin, The University of Edinburgh News. April/May 2002/03. No. 4, p. 14. Staff news pre-2009. eBulletin Archive. February 2003. Obituaries. Ruth Clayton. She was one of a group of scientists who joined the Institute at a time when it was led by C.H. Waddington and when many of the fundamental aspects of modern biology were being elucidated by forward thinking scientists at the university's King's Buildings campus.Martynoga, B. "Molecular Tinkering: The Edinburgh scientists who changed the face of modern biology". 2018. Matador Publishing Limited, Kibworth Beauchamp, UK. .Towards Dolly: Edinburgh, Roslin and the birth of modern genetics. . Leading a large and diverse research group, she applied the newly developing techniques of modern biology to fundamental questions in the fields of developmental biology and pathology of the eye and the brain. Her work was characterised by a rigorously conceptual approach, methodological innovation and a keen interest in the social and ethical implications of scientific and medical research.
Education and early life Clayton was born in London on 10 June 1925. She studied zoology at the University of Oxford, gaining an MA.
Research and career
Institute of Animal Genetics Clayton joined the Institute of Animal Genetics (University of Edinburgh) in 1947 at a time of rapid expansion under the leadership of the biologist and polymath C.H. Waddington. She was one of the original group of scientists there during the 1950s that included notable figures such as Charlotte Auerbach, Geoffrey Beale, Douglas Scott Falconer, Henrik Kacser, Eric Lucey, Eric Reeve, and Alan Robertson. Waddington's initial solution to staff accommodation problems in Edinburgh was the acquisition of the nearby Mortonhall and an experiment in collegiate living, from which Eric Reeve's wife, the artist Edith Simon drew inspiration for her novel The Past Masters (titled House of Strangers in the USA).Simon, E. The House of Strangers. 1953. G.P. Putnam's Sons, New York, USA. In 1965, the Medical Research Council and Wellcome Foundation funded the building of a modern tower block, adjacent to the main Institute of Animal Genetics Crew Building on the university's King's Buildings campus to accommodate the research being undertaken by Waddington and his colleagues.A sense of place. Towards Dolly: Edinburgh, Roslin and the birth of modern genetics. 2013. By the 1970s, Clayton, DES Truman, John Campbell, Geoffrey Selman, Joe Jacob, John Bishop, Ken Jones and their research groups occupied the tower, all pursuing different aspects of an explicitly epigenetic research programme.Falconer D. Quantitative genetics in Edinburgh: 1947–1980. Genetics. 1993 Feb;133(2):137–42. PMCID: PMC1205304. When Ruth Clayton's group outgrew the accommodation available in the tower, she refurbished and occupied the first floor of the Crew Building. She retired in 1993 with Emeritus Reader status.
Epigenetics and the eye
Epigenetics in its very broadest sense (and that originally intended by Waddington) is the study of the processes by which the information encoded in genes (the genotype) becomes manifest (is expressed) in the observable characteristics (the phenotype) of an individual during development. The eye in general and in particular the abundant proteins of the eye lens, which are termed crystallins provided Clayton and her colleague DES Truman with an ideal system in which to investigate the link between gene expression and cell differentiation during embryonic development. The complexity of crystallin protein composition and expression were explored by early adoption of a wide range of innovative immunological,Clayton RM. "Localization of embryonic antigens by antisera labelled with fluorescent dyes". Nature. 1954 Dec 4;174(4440):1059. PubMed Clayton RM, Truman DE. "Molecular structure and antigenicity of lens proteins". Nature. 1967 Jun 17;214(5094):1201-4. PubMed .Clayton RM, Campbell JC, Truman DE. "A re-examination of the organ specificity of lens antigens". Exp Eye Res. 1968 Jan;7(1):11-29. PubMed biochemical,Clayton RM, Truman DE, Campbell JC. "A method for direct assay of messenger RNA turnover for different crystallins in the chick lens". Cell Differ. 1972 Apr;1(1):25-35. PubMed Clayton RM, Truman DE. "The antigenic structure of chick beta-crystallin subunits". Exp Eye Res. 1974 May;18(5):495-506. PubMed .Truman DE, Clayton RM. "The subunit structure of chick beta-crystallins". Exp Eye Res. 1974 May;18(5):485-94. PubMed .Clayton RM, Truman DE, Hannah AI. "RNA turnover and translational regulation of specific crystallin synthesis". Cell Differ. 1974 Sep;3(3):135–45. PubMed . molecular, and cellularJackson JF, Clayton RM, Williamson R, Thomson I, Truman DE, de Pomerai DI. "Sequence complexity and tissue distribution of chick lens crystallin mRNAs". Dev Biol. 1978 Aug;65(2):383-95. PubMed .Bower DJ, Errington LH, Wainwright NR, Sime C, Morris S, Clayton RM. "Cytoplasmic RNA sequences complementary to cloned chick delta-crystallin cDNA show size heterogeneity". Biochem J. 1982 Feb 1;201(2):339–44. PubMed ; PubMed Central PMCID: PMC1163648.Errington LH, Cooper DN, Clayton RM. "The pattern of DNA methylation in the delta-crystallin genes in transdifferentiating neural retina cultures". Differentiation. 1983;24(1):33–8. PubMed Bower DJ, Errington LH, Pollock BJ, Morris S, Clayton RM. "The pattern of expression of chick delta-crystallin genes in lens differentiation and in trans-differentiating cultured tissues". EMBO J. 1983;2(3):333–8. PubMed ; PubMed Central PMCID: PMC555137.Jeanny JC, Bower DJ, Errington LH, Morris S, Clayton RM. "Cellular heterogeneity in the expression of the delta-crystallin gene in non-lens tissue". Dev Biol. 1985 Nov;112(1):94–9. PubMed . techniques then being developed in Edinburgh and elsewhere. On the basis of these and other studies she developed and advocated the view that the differences in gene expression that underlie cell differentiation are quantitative in nature and combinatorial in effect.Clayton RM, Truman DE, Bird AP. Quantitative regulation. Adv Exp Med Biol. 1982;158:327-9. PubMed Bird AP, Truman DE, Clayton RM. "The molecular basis of differentiation and competence". Adv Exp Med Biol. 1982;158:61–4. PubMed . This nuanced view contrasted markedly with the prevailing ideas at that time of a strict demarcation between “house-keeping" and “luxury" gene products, strictly tissue-specific expression of luxury gene products and a single unitary function for individual proteins.Truman DES. The Biochemistry of Cytodifferentiation. 1974. Blackwell Scientific Publications, Oxford, London, Edinburgh, Melbourne. . Crystallin gene expression was further explored in a detailed series of studies using long-term cell culture models in which progenitor chick lens cells continuously differentiated into lens fibre cells in controlled laboratory conditions. The intrinsic programme of crystallin gene expression during this process was found to be non-coordinate within and between crystallin protein classes, tightly controlled and resembled the developmental programme seen in the animal itself,Patek CE, Clayton RM. "A comparison of the changing patterns of crystallin expression in vivo, in long-term primary cultures in vitro and in response to a carcinogen". Exp Eye Res. 1985 Mar;40(3):357–78. PubMed .Patek CE, Clayton RM. "Alterations in crystallin gene expression during subculture of chick lens cells". Exp Eye Res. 1986 Oct;43(4):595–606. PubMed . but it could be modified by age, genotype, cellular growth rate, and soluble factors.Patek CE, Clayton RM. "Patterns of crystallin expression during differentiation in vitro of several chick genotypes with different effects on lens cell growth rate". Exp Eye Res. 1986 Dec;43(6):1111-26. PubMed .Patek CE, Clayton RM. "The influence of the genotype on the process of ageing of chick lens cells in vitro". Exp Cell Res. 1988 Feb;174(2):330-43. PubMed .Patek CE, Clayton RM. "Age-related changes in the response of chick lens cells during long-term culture to insulin, cyclic AMP, retinoic acid and a bovine retinal extract". Exp Eye Res. 1990 Apr;50(4):345-54. PubMed .Clayton RM, Patek CE, Head MW, Cuthbert J. "Ageing in the chick lens: in vitro studies". Mutat Res. 1991 Mar–Nov;256(2-6):203–20. Review. PubMed .Patek C, Head M, Clayton R. "Effects of age and genetic growth rate on the crystallin composition of the chick lens". Int J Dev Biol. 1994 Dec;38(4):717–24. PubMed . All of this indicated that the epigenetic programme was intrinsic to the cells, but it could be modified by external and internal variables.
Differentiation and transdifferentiation of ocular tissues