Anthony Cashmore Explained

Anthony R. Cashmore
Fields:Plant biology
Molecular biology
Workplaces:University of Pennsylvania
Rockefeller University
Alma Mater:University of Auckland
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Known For:Discovery of cryptochrome, the blue light photoreceptor in Arabidopsis
Awards:Elected Member of the National Academy of Sciences
Spouse:Nancy Bonini
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Anthony R. Cashmore (b. 22 Jan 1941)[1] is a biochemist and plant molecular biologist, best known for identifying cryptochrome photoreceptor proteins.[2] [3] [4] [5] These specialized proteins are critical for plant development and play an essential role in circadian rhythms of plants and animals.[4] [5] [6] [7] A Professor emeritus in the Department of Biology at the University of Pennsylvania, Cashmore led the Plant Science Institute from the time of his appointment in 1986 until his retirement in 2011.[8] He was elected to the National Academy of Sciences in 2003.

Early life and education

Born in Auckland (New Zealand) in 1941, Cashmore grew up in Manawaru and Te Aroha. As a teenager, Cashmore worked in Palmerston North in the Grasslands Division of New Zealand's Department of Scientific and Industrial Research (DSIR).

Cashmore enrolled at the University of Auckland, majoring in chemistry and completing a Bachelor of Science degree in 1962, Master of Science degree in 1963, and Ph.D. degree in 1966.[1] In 1968 Cashmore moved to Cambridge (UK) to pursue postdoctoral studies at the University of Cambridge Department of Chemistry, and later at the MRC Laboratory of Molecular Biology.[1] In 1971 Cashmore moved to the United States, where he worked as a Research Associate in the laboratory of Michael Chamberlin at the University of California, Berkeley before returning to New Zealand.[1]

In 1979, Cashmore took a position at the Rockefeller University (New York), first as a visiting scientist in the laboratory of Nam-Hai Chua, and then as an assistant professor, then Associate Professor.[9] In 1986, Cashmore was appointed the Director of the Plant Science Institute at the University of Pennsylvania (Philadelphia).[4] [1] He retired in 2011 and is currently an Emeritus Professor of Biology at the University of Pennsylvania.[8]

Career

Prostratin

During his PhD studies, Cashmore purified the toxic component of Pimelea prostrata, a New Zealand toxic shrub. Using partition chromatography, Cashmore purified and crystallized the active component, referred to as prostratin. Cashmore's studies showed that prostratin was strikingly similar to the co-carcinogenic phorbol esters of croton oil, a relationship that was subsequently confirmed using chemical synthesis[10] and x-ray crystallography approaches.[11]

Nucleic acid chemistry

Hydrazine degradation

Working with George Petersen (a New Zealand biochemist) at New Zealand's Department of Scientific and Industrial Research (DSIR) (Palmerston North), Cashmore was introduced to the study of nucleic acids and how selective chemical reagents could be used to determine the nucleic acid sequence of DNA.[12] Cashmore and Petersen examined the use of hydrazine as a tool to measure purine nucleotides in samples of DNA.[13] [14] Recognizing that hydrazine-treated DNA subsequently exposed to alkali conditions undergoes degradation, Cashmore defined a quantitative technique for measuring purine nucleotides in DNA samples.[13] Subsequently, Allan Maxam and Walter Gilbert employed the hydrazine degradation approach to develop Maxam–Gilbert sequencing, the first widely adopted method for DNA sequencing.[15]

tRNA

Working with Dan Brown[16] at Cambridge University, Cashmore demonstrated that the reagent methoxyamine reacted with a limited number of cytosine residues in tRNA. Later, Cashmore used the RNA sequencing procedure that had recently been developed by Fred Sanger to identify the reactive cytosine residues in a tyrosine suppressor tRNA of Escherichia coli.[17] Studying a mutant of this tRNA, Cashmore identified a new reactive cytosine residue at the base of loop III.[18] This finding suggested that base pairing of conserved residues occurred supporting one of the early models proposed for the three dimensional structure of transfer RNA.[19]

Biosynthesis of RuBisCO

Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), thought to be the world's most abundant protein,[20] utilizes photosynthetic energy to fix carbon dioxide through the conversion of ribulose-1,5-bisphosphate to two molecules of 3-phosphoglycerate. It is an enzyme of interest in the field of climate change due to its role in fixing carbon dioxide.[21] [22] At New Zealand's DSIR Palmerston North,[23] Cashmore studied the biosynthesis of RuBisCO, a multi-subunit (eight large and eight small subunits) protein located in plant chloroplasts. Using selective inhibitors of protein synthesis Cashmore showed that in contrast to the RuBisCO large subunit (which was known to be synthesized on chloroplast ribosomes), the small subunit of RuBisCO was produced as a soluble precursor protein on cytoplasmic ribosomes.[24] The soluble precursor protein is subsequently processed and imported into chloroplasts.[25] [26]

Light-regulated enhancer sequences

At Rockefeller University, Cashmore studied DNA sequences associated with light regulated expression of a pea nuclear RuBisCO small subunit gene.[27] For these studies, Cashmore collaborated with scientists in the laboratory of Jeff Schell and Marc Van Montagu in Ghent (Belgium).[28] Using transgenic plant cells, they demonstrated that in the pea plant, light-regulated expression was mediated by a 1 kilobase (kb) promoter fragment.[27] In a second study, this DNA fragment was shown to have the properties of an enhancer sequence, functioning in either orientation and when fused to a normally non-light-regulated promoter.[29]

Cryptochrome

In 1881, Francis Darwin and Charles Darwin demonstrated that plants exhibited a phototropic response to blue light.[30] [31] [32] Elusive to discovery, scientists gave the name cryptochrome to the photoreceptor factor(s) responsible for this effect.[33] Interested in adopting the "power of Arabidopsis genetics" for the study of light regulation,[7] in 1980 Cashmore, working with post-doctoral student Margaret Ahmad, identified Arabidopsis mutants that showed reduced sensitivity to blue light. Using DNA sequencing and complementation techniques, Cashmore and Ahmed cloned the gene and discovered that the mutants were alleles of a previously identified hy4 mutant.[5] Ahmad and Cashmore called this blue light photoreceptor "cryptochrome", and it is now referred to as CRY1.[5] [34] Cashmore's research group identified a second member of the cryptochrome family (CRY2) using cDNA library screening.[4] This research was the foundation that led to the identification of CRY proteins in other plant species, bacteria, fungi, animals, and humans, as well as research that defined the pivotal role of these proteins in circadian clock regulation across species[7] [35] and as the primary sensory molecule enabling light-dependent magnetic compass orientation in migratory birds.[36] Today, light-based diagnostic and therapeutic wearable photonic healthcare devices, are based on the function of the cryptochrome photoreceptors.[37]

Human behavior, free will and consciousness

In recent years, Cashmore turned his attention to the topic of human behavior, studying the concepts of free will and consciousness. In a publication on this topic,[38] Cashmore noted that in popular discussions regarding the relative importance of nature vs nurture, an element that is commonly missing is awareness that individuals are responsible for neither their genetic inheritance nor their environment.[38] Based on this observation, he therefore asked "where does this notion of free will come from?" and challenged the scientific community to reconsider the concept of free will.[38] [39]

Applying the scientific method to probe the concept from a Philosophy of Information approach, Cashmore argued that all biological systems – including humans – obey the laws of chemistry and physics. Cashmore further suggested that the concept of free will "is an illusion, akin to religious beliefs or the outdated belief in vitalism", equivalent to the continuing belief in Cartesian duality, and therefore contradictory to society's interpretation of accountability in the criminal justice system.[38] [40] The article stimulated discussion and analysis by scientists in the fields of biology, behavioral sciences, and philosophy.[41] Scientist and author Jerry Coyne stated that after reading this article on determinism and the criminal justice system, he was ‘instantly converted to determinism’.[42] [43] [44]

Honors and awards

Cashmore was a Professor of Biology at the University of Pennsylvania and Director of the Plant Science Institute there until his retirement in 2011. Since 2011, he has been a Professor emeritus at the University of Pennsylvania (Department of Biology). Cashmore has authored more than 100 refereed research papers and has served on the editorial boards of the publications Plant Molecular Biology, The Plant Journal, and the Proceedings of the National Academy of Sciences of the United States of America.[45] He was elected to the National Academy of Sciences in 2003.[46] [47]

Selected publications

Journal articles

Patents

Book chapters

Personal life

Cashmore was born in Auckland (New Zealand), to parents Nancy and Norman Cashmore.[49] He is married to American Neuroscientist and Geneticist Nancy Bonini.[50]

External links

• Google Scholar - Anthony R. Cashmore

Notes and References

  1. Web site: Curriculum Vitae, ANTHONY R. CASHMORE . . 2019 . upenn.edu . University of Pennsylvania. 13 Nov 2019 .
  2. Web site: It's About Time: Biological Clock Research Keeps Ticking. dead. https://web.archive.org/web/20050521234446/https://www.eurekalert.org/pub_releases/1998-12/NIoG-IATB-231298.php. 21 May 2005 . . 23 Dec 1998 . eurekalaert.org. . 10 Jan 2020.
  3. Book: Michael F. Holick. Ernst G. Jung. Biologic Effects of Light 1998: Proceedings of a Symposium Basel, Switzerland November 1–3, 1998. 23 January 2020. 6 December 2012. Springer Science & Business Media. 978-1-4615-5051-8.
  4. Lin . C . Yang . H. Guo. H. T. Mockler. Chen. J. Cashmore. AR. 1998. Enhancement of blue-light sensitivity of Arabidopsis seedlings by a blue light receptor cryptochrome 2 . . 95. 5. 2686–2690. 10.1073/pnas.95.5.2686. 9482948 . 19462 . 1998PNAS...95.2686L . free .
  5. Ahmad. M . Cashmore. AR. 1993 . HY4 gene of A. thaliana encodes a protein with characteristics of a blue-light photoreceptor. Nature. 366. 6451. 162–166 . 10.1038/366162a0. 8232555 . 1993Natur.366..162A . 4256360 . 25 Jan 2020.
  6. Book: Garry C. Whitelam. Karen J. Halliday. Annual Plant Reviews, Light and Plant Development. 8 April 2021. 15 April 2008. John Wiley & Sons. 978-0-470-99429-0. 17–.
  7. News: Miller. Susan Katz . 20 Nov 1993 . Science: Darwin's plants give up their 'blue' secrets. New Scientist. 8 Apr 2021.
  8. Web site: Retired/Emeritus Faculty . . 2020 . Penn Arts & Sciences Department of Biology . The Trustees of the University of Pennsylvania . 4 Jan 2020 .
  9. Web site: Plant Biology Tree: Anthony Robert Cashmore . The Academic Family Tree . 2021 . 13 Mar 2021.
  10. CASHMORE AR, SEELYE RN, CAIN BF . The structure of prostratin : A toxic tetracyclic diterpene ester from Pimelea Prostrata . 1976 . Tetrahedron Letters. 17 . 20. 1737–1738 . 10.1016/S0040-4039(00)92940-X. 8 Apr 2021.
  11. McCormick . IRN . Nixon. PE. Waters. TN . 1976. On the structure of prostratin: An X-ray study . Tetrahedron Letters . 17 . 20 . 1735–1736 . 10.1016/S0040-4039(00)92939-3. 7 Jul 2021.
  12. Nair . Prashant . 11 Jan 2011. Profile of Anthony R. Cashmore . Proceedings of the National Academy of Sciences of the United States of America . 108 . 2 . 443–5 . 10.1073/pnas.1018069108. 21191100 . 3021040 . 2011PNAS..108..443N . free .
  13. Cashmore . AR . Petersen. GB . 1969 . The degradation of DNA by hydrazine: A critical study of the suitability of the reaction for the quantitative determination of purine nucleotide sequences . Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis. 174 . 2. 591–603. 10.1016/0005-2787(69)90289-5. 4888872 . 28 Jan 2020.
  14. Cashmore . AC . Petersen. GB . 1978. The degradation of DNA by hydrazine: identification of 3-ureidopyrazole as a product of the hydrazinolysis of deoxycytidylic acid residues . Nucleic Acids Research. 5 . 7. 2485–2491 . 10.1093/nar/5.7.2485. 353742 . 342178 .
  15. Maxam . AM . Walter Gilbert . Gilbert . W . 1977 . A new method for sequencing DNA . . 74 . 2 . 560–564. 10.1073/pnas.74.2.560. 265521 . 392330 . 1977PNAS...74..560M . free . Allan Maxam .
  16. Gait . Michael J. . 7 Nov 2018 . Memoirs: Daniel McGillivray Brown. 3 February 1923—24 April 2012 . . 66. 79–100. 10.1098/rsbm.2018.0008 . 81639128 . free .
  17. Cashmore. AR . Brown . DB. Smith. JD. 1971 . Selective reaction of methoxyamine with cytosine bases in tyrosine transfer ribonucleic acid . . 59. 2. 359–373 . 10.1016/0022-2836(71)90056-8. 4935788 . 15 Mar 2021. subscription.
  18. Cashmore . T . 1971 . Interaction between Loops I and III in the Tyrosine Suppressor tRNA. Nature New Biology. 230 . 16. 236–239. 10.1038/newbio230236a0. 5280403 . 10 Jul 2021.
  19. Levitt . M. 1969 . Detailed molecular model for transfer ribonucleic acid. Nature . 224 . 5221. 759–763 . 10.1038/224759a0. 5361649. 1969Natur.224..759L. 983981. 10 Jul 2021.
  20. Yinon . Bar-On. Ron. Milo. 5 Mar 2019 . The global mass and average rate of rubisco . . 116 . 10. 4738–4743 . 10.1073/pnas.1816654116. 30782794. 6410859. free.
  21. Dobberstein . B . Blobel. G . Cjua. NH . 1 Mar 1977 . In vitro synthesis and processing of a putative precursor for the small subunit of ribulose-1,5-bisphosphate carboxylase of Chlamydomonas reinhardtii. . 74 . 3 . 1082–1085 . 10.1073/pnas.74.3.1082. 265554 . 430598 . 1977PNAS...74.1082D . free .
  22. Web site: Will Rubisco stop global warming?. Cohen . Mati. www.economarks.com . Economarks. 13 Nov 2021 .
  23. Cashmore. AR . 1976 . Protein Synthesis in Plant Leaf Tissue: The sites of synthesis of the major proteins . . 251. 9 . 2848–2853. 10.1016/S0021-9258(17)33567-6. 1262350 . 19 Jan 2020 . free .
  24. Gray . RE . Cashmore . A. Broadhurst. K . 1978 . Cell-free synthesis of leaf protein: Identification of an apparent precursor of the small subunit of ribulose-1,5-bisphosphate carboxylase . . 108 . 2. 595–608 . 10.1073/pnas.75.2.655. 16592495 . 411314 . 1978PNAS...75..655C . 21 Jul 2021. free .
  25. Highfield . PE . Ellis . RJ . 2 Feb 1978 . Synthesis and transport of the small subunit of chloroplast ribulose bisphosphate carboxylase . Nature . 271 . 5644. 420–424 . 10.1038/271420a0. 1978Natur.271..420H . 4188202 . 28 Nov 2021.
  26. Lubben . TH . Theg . SM. Keegstra. K . 1988. Transport of proteins into chloroplasts. Photosynthesis Research . 17. 1–2. 173–194 . 10.1007/BF00047688. 24429668 . 922287 . 28 Nov 2021.
  27. Herrera-Estrella . L . Van den Broeck. G. Van Montagu . M. Schell. J. Timko. M. Cashmore. A . 1984 . Light-inducible and chloroplast-associated expression of a chimaeric gene introduced into Nicotiana tabacum using a Ti plasmid vector . Nature. 310 . 5973. 115–120 . 10.1038/310115a0. 6330570 . 1984Natur.310..115H . 4307727 . 26 Nov 2021.
  28. Estrella . Luis . My journey into the birth of plant transgenesis and its impact on modern plant biology. Biography of Pioneers in Plant Biotechnology. 2020 . 18. 7. 1487–1491. 10.1111/pbi.13319. 31883186 . 7292536 .
  29. Timko . M . Kausch. A. Castresana. C. Fassler. J. Herrera-Estrella. L. Van den Broeck. G. Van Montagu. M. Schell. J. Cashmore. A. 1985. Light regulation of plant gene expression by an upstream enhancer-like element . . 318 . 6046. 579–582. 10.1038/318579a0. 3865055 . 1985Natur.318..579T . 4307881 . 15 Dec 2019 .
  30. Miller . Susan Katz . 20 Nov 1993 . Science: Darwin's plants give up their 'blue' secrets . . 8 Dec 2019 .
  31. Briggs. Winslow . 1993. New light on stem growth . . 366. 6451. 110–111 . 10.1038/366110a0. 8232548 . 1993Natur.366..110B . 42260720 . 5 Jan 2020 .
  32. Book: Darwin, Charles . The Power of Movement in Plants . 1881 . D. Appleton and Company . New York.
  33. Gressel. J. 1979. Blue Light Photoreception. Photochemistry and Photobiology. 30. 6. 749–754. 10.1111/j.1751-1097.1979.tb07209.x. 98643540. 28 Nov 2021.
  34. Lin . C. Robertson . D. Raibekas. A. Jorns. M. Dutton. P. Cashmore. A . 1995. Association of flavin adenine dinucleotide with the Arabidopsis blue light receptor CRY1 . Science . 269 . 5226. 968–970. 10.1126/science.7638620. 7638620. 1995Sci...269..968L. 40649563. 30 Dec 2021.
  35. Web site: Scientific Background Discoveries of Molecular Mechanisms Controlling the Circadian Rhythm. Hall . Jeffrey. Rosbach. Michael. Young. Michael. 2017. nobelprize.org . Nobel Prize Outreach . 10 Dec 2021.
  36. Einwich . Angelika. Dedek . Karin. Seth. Pranav Kumar. Laubinger. Sascha. Mouritsen. Henrik. 25 Sep 2020. A novel isoform of cryptochrome 4 (Cry4b) is expressed in the retina of a night-migratory songbird . Scientific Reports . 10 . 1. 15794 . 10.1038/s41598-020-72579-2. 32978454. 7519125. 2020NatSR..1015794E.
  37. Lee . G-H . Moon . H. Kim. H. Lee. GH. Kwon. W. Yoo. S. Myung. D. Yun. SH. Bao. Z. Hahn. SK . 2020 . Multifunctional materials for implantable and wearable photonic healthcare devices . Nature Reviews Materials. 5. 2. 149–165. 10.1038/s41578-019-0167-3 . 32728478 . 7388681 . 2020NatRM...5..149L .
  38. Cashmore . AR . 2010. The Lucretian swerve: The biological basis of human behavior and the criminal justice system . . 107. 10. 4499–4504. 10.1073/pnas.0915161107. 20142481 . 2842067 . free .
  39. Web site: Anthony Cashmore . . informationphilosopher.com. Bob Doyle . 28 Jan 2020 .
  40. Book: Gregg D. Caruso. Exploring the Illusion of Free Will and Moral Responsibility. 28 January 2020. 5 July 2013. Lexington Books. 978-0-7391-7732-7. 186–.
  41. Book: Lubomira Radoilska. Autonomy and Mental Disorder. 28 January 2020. 19 April 2012. OUP Oxford. 978-0-19-959542-6. 33–.
  42. News: Harris. Lee . 2018. Meet Jerry Coyne, the University's Most Prolific and Provocative Emeritus Blogger. https://web.archive.org/web/20181116050934/https://www.chicagomaroon.com/article/2018/2/15/meet-jerry-coyne-universitys-prolific-provocative/. 16 November 2018. . Chicago, USA. 30 Dec 2019 .
  43. Book: Alfred R. Mele. Free: Why Science Hasn't Disproved Free Will. 5 Jan 2020. 2 September 2014. Oxford University Press. 978-0-19-937164-8. 53–.
  44. Web site: Free will is an illusion, biologist says . Zyga. Lisa . 2010 . phys.org. Science X. 20 Dec 2019 .
  45. Web site: About the PNAS Member Editor: Anthony Cashmore. . 2021. National Academy of Sciences. National Academy of Sciences. 22 Dec 2021 .
  46. Web site: Plant Biologist Anthony Cashmore Elected to National Academy of Sciences . . 5 May 2003 . penntoday.upenn.edu . University of Pennsylvania . 13 Nov 2019 .
  47. Web site: Member Directory: Anthony Cashmore. . 2021. . National Academy of Sciences . 8 Apr 2021 . http://www.nasonline.org/member-directory/members/20002156.html
  48. Book: Amita Sehgal. Molecular Biology of Circadian Rhythms. 13 November 2019. April 2004. John Wiley & Sons. 978-0-471-41824-5. 185–. Chapter 8: Physiological and molecular characteristics of plant circadian clocks.
  49. Web site: Town Topics . . 2019 . geneanet.org . Geneanet . 13 Nov 2019 .
  50. News: Kelly. Morgan. Geoscientist William Bonini, dedicated teacher and genial colleague, dies at 90 . Princeton University News. Princeton, NJ, USA . 3 Jan 2017 . 12 Jul 2019.

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