Claude Bernard legacy and C. elegans genomics

1. Claude Bernard legacy and C. elegans genomics

2. ‘‘Simply gathering data without having any specific question in mind is an approach to science that many people are doubtful about. Modern science is supposed to be mostly hypothesis-driven’. . . .My first studies of the worm lineage didn’t require me to ask a question (other than ‘What happens next?’). They were pure observation, gathering data for the sake of seeing the whole picture. . . . This kind of project suits me—it’s never bothered me that it doesn’t involve bold theories or sudden leaps of understanding, or indeed that it doesn’t usually attract the same level of recognition as they do.’’ John Sulston (2002) [in Kell & Olliver, 2003]

3. Here is what he got The C. elegans cell lineage

4. CLAUDE BERNARD (1813-1878)

5. Claude Bernard surrounded by his pupils during one of his many experiments Claude Bernard model organism The original is in the Department of Physiology, School of Medicine, Paris. Painting by L'Hermitte

6. 1843 Medical degree with the dissertation: "Du suc gastrique et de son rôle dans l'a nutrition" 1854 Doctor in Natural Sciences. Shows that the liver is where gluconeogenesis occurs 1839-1843 Works with François Magendie (1783-1855) after being ranked 26th of 29 students for internship 1868 Elected to the Académie Française 1831 Works as a "factotum" in a pharmacy em Vaise near Lyon after being turned down at the "baccalauréat" exam 1865 Publishes the book "Introduction a l´Etude de La Médicine Expérimentale" 1844 Resigns to the research assistanship and is left in financial straits. February 9, 1878 CB dies at 9:00 pm and is burried with national honors July 12, 1813 CB is born near the village of Saint-Julien sous-Montmélas, Beaujolais, 7 km from Villefranche-sur-Saône 1843 1823 1833 1853 1863 1873 CLAUDE BERNARD

7. more on induction, etc. in: Kell & Oliver in: BioEssays26, 99-105, 2003 more about Claude Bernard, his life and ideas in: Conti F., Nature Rev. Mol. Cell Biol.2, 703-708, 2001 Bernard never opposed observation to experimentation, on the contrary... The scientist is a person that embraces both theory and experimental practice. 1st he observes a fact; 2nd upon this fact, an idea is born in his spirit; 3rd using this idea and reasoning he conceives an experiment, imagine and set up the conditions for it; 4th from this experiment result new phenomena that he observes, and so on. [the scientist] ...is always posed between two observations: one that is the beginning of his reasoning, and the other that serves as a conclusion.

8. Nematode worms

9. Parasitic infections of man Modified from: “Topics in Internatl. Health – Schistosomiasis” The Wellcome Trust

10. Plant parasitic Nematodes Nematodes predate on many crops worldwide, and the economic losses caused are estimated to be in the order of US$77 billion each year. source: Jung, C. et al. (1998), Trends Plant Sci.3:266, 1998

11. New nematode phylogeny derived from analysis of 300 nematode SSU rRNA sequences + morphological caracters source: Blaxter M (2003) Adv. Parasitol.54:101-195

12. 2002 source: Ankeny (2001), Nature Reviews Genet. 2:474-479

13. A highly connected part of the C.elegans interactome A subnetwork around VAB-3 and C49A 1.4 (developmental homeobox proteins) Source: Li S et al (2004) Science 303(5657):540-3

14. C. elegans O. tipulae Morphology source: Winter (1995) http://icb.usp.br/~cewinter/sem.html Cell Biology source: Dichtel-Danjoy & Félix (2004) TIG20:268-276 Oscheius tipulae and Caenorhabditis elegans

15. M. luteus HB101 C. elegans M. luteus C. elegans M. luteus CEW1 • = 1.7007 g/cm3 GC% = 41,53 • = 1.6953 g/cm3 GC% = 36,00 The genome of O. tipulae I – GC content CsCl/acrylamide centrifugation Initial Density – 1.7284 g/cm3 60k rpm/ 40 hr/ 20 0C rotor - TLA 120.2 Source: Ahn & Winter, in preparation

16. The genome of O. tipulae II – reassociation curve Source: Ahn (2004)

17. The genome of O. tipulae III – size and composition Source: Ahn (2004)

18. O. tipulae E. coli The genome of O. tipulae IV – the rapid fraction Source: Ahn (2004)

19. Telomeres of O. tipulae Source: Ahn (2004)

20. The eEF1A genes of O. tipulae Source: Akamine (2004)

21. Why eEF1A genes cannot be used for phylogenetic analysis Source: Akamine (2004)

22. GC content in transcribed genes of O. tipulae C. elegans O. tipulae

23. Dr Cristiane Penha-Scarabotto Dr Rubens Nobumoto Akamine (eEF1A) Joselene Pereira de Moura Daniela Peres Almenara Il-Young Ahn (DNA characterization) Juliana Machado Andreoni Thomas Blumenthal - University of Colorado/Denver (vtg/operons) Marie-Anne Félix - Universidade de Paris (evolution of O. tipulae) Acknowledgements Supported by

25. 1820 Ampère introduces electro-dynamics 1822 Champollion decifers the hyeroglyphs 1824 Beethoven composes the ninth symphony 1827 Ohm introduces the law on the electric current 1829 Lobatchevski publishes his works on the principles of geometry 1836 Berzelius discovers catalysis 1838 Schwann discovers the animal cell 1846 Le Verrier discovers the planet Neptune 1847 Marx and Engles write the Manifest of the communist party 1859 Darwin publishes "On the origin of species..." 1865 Mendel publishes his paper on the law of heredity 1869 Mendeleyev makes the classification of chemical elements 1867 Pasteur publishes his work on fermentation 1878 Nietzsche publishes "Human All-too-Human" Events that occurred during Claude Bernard lifetime

26. or... Very diverse circunstances can be at the starting point of a scientific investigation... 1st Experimental research has an observation as a beginning. 2nd Experimental research has a hypothesis or theory as a starting point. Experience is but an induced observation ...in the experimental method, experiment and observation always go together."

27. Theoretical basis of Bernard's thoughts • Bernard’s physiology rests on three conceptual • pillars: • determinism, • the rejection of teleology and metaphysics • overcoming the dependence on anatomy • Bernard’s determinism was ‘absolute’: • it concerned both inanimate objects and living organisms; • it stated that a phenomenon shall not occur differently given the same conditions; • it applied to the psychic sphere

28. Some of Bernard´s ideas sound as truisms today, but they set the foundations for the second revolution of biomedical sciences ... I would say that the researcher makes questions to Nature; There are two operations to be considered in an experiment. The first consists in planning and carrying through the conditions of the experiment; the second consists in verifying the results. It is not possible to begin an experiment without a preconceived idea; doing an experiment, we have already said, is making a question; we cannot conceive a question without the idea that requires the answer

29. Bernard was a foreteller of the revolution brought to Biology by the Physical and Chemical Sciences "... each manifestation of living creatures is a physiological phenomenon and ... it depends on definite physico-chemical conditions. This is absolute determinism: it expresses the fact that the psychic sphere cannot do without the physico-chemical world." Claude Bernard, 1878-79