Draft:Dr. Martin Ralph

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This article is about chronobiologist Dr. Martin Ralph. For the Australian canoeist, see Martin Ralph.

Dr. Martin Ralph is a chronobiologist best known for his research on the Tau mutant hamster.

Biography[edit]

Martin Ralph attended Stanford University from 1972 to 1976 and earned a Bachelor’s degree in general biology. He had the opportunity to study biological clocks through the honors program in the laboratory of Colin Pittendrigh, who is known as the legendary pioneer of chronobiology. Ralph’s project focused on the adaptability of Drosophila melanogaster eclosion time[1], which was the key experiment of Pittendrigh and his team that resulted in the development of phase response curves and non-parametric entrainment model. He was a graduate student at University of Oregon where he was part of the neuroscience program. Under the supervision of Michael Menaker, his laboratory mentor, Ralph earned his doctoral degree in 1986 with his work in neuropharmacology of circadian responses to light. In the same year, he came to University of Virginia, where he worked as a post-doctoral researcher under the guidance of Gene Block. There, he studied the circadian systems in the eyes of marine snails to investigate photic transduction.[1] Ralph’s work was one of the projects in the Block laboratory that led to the establishment of the persistence of circadian rhythm in the isolated basal retinal neuron (BRN) and to the discovery of necessity of potassium ion conductance in generating the circadian rhythms. He is currently a professor of psychology at the University of Toronto, where he has served as a faculty member since July 1989 and made many contributions to the field of chronobiology and psychology.[2]

Research[edit]

Tau mutant hamster[edit]

A comparison of the actograms of a wild type (left) and a homozygous tau mutant hamster (right). The wild-type hamster has a free-running period of about 24 hours, while the tau mutant has a free-running period of about 20 hours.

As a graduate student in the Menaker laboratory at the University of Oregon, Ralph discovered the Tau mutation in the casein kinase 1 isoform epsilon (CKIε) gene in hamsters[3], which resulted in a free-running period, a measurement of how long the intrinsic rhythm of an organism takes to repeat without environmental signals, of about 20 hours when homozygous and 22 hours when heterozygous for the mutation.[4] The normal free-running period for hamsters is about 24 hours[4], which is similar to other mammals. CKIε plays an important regulatory role for circadian rhythms through the phosphorylation of the proteins PER and CRY, which control the circadian rhythm by acting as negative regulators in the transcription translation feedback loop in mammals. The Tau mutation was the first mutation found to alter circadian rhythms in mammals and has been used as a model to study circadian rhythms. This mutation involves a single amino acid substitution in the gene that causes the enzyme to be slower at phosphorylating PER and CRY and ultimately results in a shorter period.[5] In 1988, he performed experiments that involve transplanting the suprachiasmatic nucleus, or SCN, of hamsters with varying free-running periods into hamsters with ablated SCNs. [6] He found that the hamsters with transplanted SCNs took on the free-running period of the donor hamster.[7][8] His results support the hypothesis that the SCN is the master clock that controls many outputs which oscillate with a 24 hour period in the mammalian system.[9][10] His experiment as well as many subsequent studies have led to the current theory that the SCN is the master clock.[11]

Other research[edit]

In 1999, Ralph collaborated with Mark Hurd at the University of Houston on a study that demonstrated how transplantation of a new clock into an aging hamster induced a roughly 20 percent increase in the average lifespan of the hamsters compared to controls without the transplant.[12]

His more recent work has concerned wide-ranging topics, including the neurochemical mechanisms underlying time-place preference and avoidance conditioning memory in mammals, circadian regulation of voluntary locomotion, and the effects of chronotype on job satisfaction.[13]

Current research interests and work[edit]

As a professor in the Department of Psychology at the University of Toronto, Ralph's current research interests include circadian rhythms, cell culture, immediate early genes, the suprachiasmatic nucleus and transplantation[14].

As of 2017, Ralph is a team member on a Canada Brain Research Fund grant titled "The Aging Brain: Circadian, Transcriptomic, and Epigenomic Dimensions" with Art Petronis, Jose Nobrega and Albert Wong. The project aims to determine how the breakdown of the body's circadian rhythm and changes in the epigenome are related to the aging process. The team is currently collecting mice brains at a range of ages and characterizing their transcriptional, epigenetic and circadian rhythm signatures, identifying which of these patterns are affected by age, and analyzing how these might relate to aging brain diseases.[15]

Participation in the chronobiology research community[edit]

Participation in conferences[edit]

May 2006: session chair at the Society for Research on Biological Rhythms (SRBR). He presented a talk titled "Implicit Time Memory".[16]

May 2007: presented a talk titled "On temporal disorganization in living systems" session at the Chronobiology Gordon Research Conference. [17]

May 2010: session chair at the SRBR conference. He presented a talk titled "Regulation of circadian period by neuronal Agrin and the a3 isoform of Na+/K+ ATPase (ATP1A3)".[18]

May 2012: presented a talk at the SRBR conference titled "Circadian Entrainment by Light and Host in the Haematophagous Chagas Vector, Triatoma infestans".[19]

Opinions about the field of chronobiology[edit]

On June 14, 2000, the Brazilian Society of Neuroscience and Behavior (SBNeC) held an electronic symposium called "The brain decade in debate: IV. Chronobiology" in which Ralph was invited to be a member of an international panel of chronobiologists[20].

When asked about what he thought would be the main questions of chronobiology to be formulated and eventually answered in the next decade, Ralph responded with four broad areas of inquiry:

  1. identify genes related to circadian rhythms
  2. relate circadian rhythms to human experience
  3. relate rhythmicity to other aspects of behavior
  4. identify new models of circadian systems

Regarding the application of chronobiological research, Ralph said:

"...humans will consider something important if it has immediate consequences. Chrono-issues have the problem that they are important in the long term, but we can ignore them for short-term gain. So, any type of medical intervention that is based on this precept will take a back seat to an immediate cure. We can ignore short-term sleep deprivation if it will gain us an edge in business, for example, not considering the fact that we may impose the deprivation for years. What hope is there of finding an acceptable chronopharmaceutical, if the public can easily dismiss the warnings."[20]

Along similar lines, he also asserted:

"The problem for chronobiology as I see it is that we are dealing with a problem that manifests itself in populations rather than in individuals. Everyone knows that cancer and heart disease can kill the individual, but sleep deprivation on the population scale causes what? More accidents perhaps, and a shorter life span, if my data are to be believed."[20]

Positions[edit]

Member of Society for Research on Biological Rhythms (1988-Present)

Member of European Biological Rhythms Society (2011-Present)

Member of Canadian Society for Chronobiology (2013-Present) [1]

Awards[edit]

He won a fellowship from A.P. Sloan Foundation on October 15, 1991, which supported his research projects involving SCN culture and transplantations. [1]

See also[edit]


References[edit]

  1. ^ a b c d "Martin Ralph". Loop Research Network-Frontiers. Retrieved 11 April 2019.
  2. ^ "Martin Ralph". University of Toronto: Collaborative Program in Neuroscience (CPIN). University of Toronto. Retrieved 11 April 2019.
  3. ^ Loudon, A. S. I.; Meng, Q. J.; Maywood, E. S.; Bechtold, D. A.; Boot-Handford, R. P.; Hastings, M. H. (2007). "The biology of the circadian Ck1epsilon tau mutation in mice and Syrian hamsters: a tale of two species". Cold Spring Harbor Symposia on Quantitative Biology. 72: 261–271. doi:10.1101/sqb.2007.72.073. ISSN 0091-7451. PMID 18522517.
  4. ^ a b PhD, Roberto Refinetti (2016-04-21). Circadian Physiology. CRC Press. ISBN 9781466514980.
  5. ^ "Gene Mutation Upsets Mammalian Biological Clock". HHMI.org. Retrieved 2019-04-10.
  6. ^ Blakeslee, Sandra (1988-11-29). "Experimental Transplant Alters Biological 'Clock'". The New York Times. ISSN 0362-4331. Retrieved 2019-04-10.
  7. ^ Roenneberg, Till (2012-08-25). Internal Time: Chronotypes, Social Jet Lag, and Why You're So Tired. Harvard University Press. ISBN 9780674065482.
  8. ^ Ralph, M. R.; Lehman, M. N. (August 1991). "Transplantation: a new tool in the analysis of the mammalian hypothalamic circadian pacemaker". Trends in Neurosciences. 14 (8): 362–366. doi:10.1016/0166-2236(91)90164-P. ISSN 0166-2236. PMID 1721743.
  9. ^ Reppert, S.; Moore, R. (1991). Suprachiasmatic Nucleus: The Mind's Clock. Oxford University Press. ISBN 9780195062502.
  10. ^ Blakeslee, Sandra (1988-11-29). "Experimental Transplant Alters Biological 'Clock'". The New York Times. ISSN 0362-4331. Retrieved 2019-04-10.
  11. ^ "Gene Mutation Upsets Mammalian Biological Clock". HHMI.org. Retrieved 2019-04-11.
  12. ^ "Research Links Healthy Biological Clock To Longevity". ScienceDaily. Retrieved 2019-04-11.
  13. ^ "Martin R. Ralph - Publications". neurotree.org. Retrieved 2019-04-25.
  14. ^ "Martin R Ralph*". www.neuroscience.utoronto.ca. Retrieved 2019-04-11.
  15. ^ "The Aging Brain: Circadian, Transcriptomic, and Epigenomic Dimensions". Brain Canada. Retrieved 2019-04-11.
  16. ^ Tenth Meeting, Society for Research on Biological Rhythms: Program and Abstracts https://srbr.org/wp-content/uploads/2015/02/SRBR_2006_Program.pdf
  17. ^ "2007 Chronobiology Conference GRC". www.grc.org. Retrieved 2019-04-11.
  18. ^ 12th Biennial Meeting, Society for Research on Biological Rhythms Program and Abstracts https://srbr.org/wp-content/uploads/2015/02/SRBR_2010_Final_Program.pdf
  19. ^ 13th Biennial Meeting, Society for Research on Biological Rhythms Conference Program https://srbr.org/wp-content/uploads/2015/02/SRBR2012ProgramOverview.pdf
  20. ^ a b c Menna-Barreto, L.; Valdez-Ramirez, P.; Ralph, M.; Monk, T. H.; Menezes, A. a. L.; Marques, N.; Markus, R.; Cornélissen, G.; Cipolla-Neto, J. (July 2001). "The brain decade in debate: IV. Chronobiology". Brazilian Journal of Medical and Biological Research. 34 (7): 831–841. doi:10.1590/S0100-879X2001000700001. ISSN 0100-879X. PMID 11449300.