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Looking for the appropriate size: genetics under control

Looking for the appropriate size: genetics under control. Crazy about Biomedicine – May 2013 Ana Ferreira Development and Growth Control Lab. Summary. I. Genetics Definition Mendelian Genetics Drosophila melanogaster: The F ruit Fly Historical view of the fly

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Looking for the appropriate size: genetics under control

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  1. Looking for the appropriate size: genetics under control Crazy about Biomedicine– May 2013 Ana Ferreira Development and Growth Control Lab

  2. Summary I. Genetics Definition Mendelian Genetics Drosophila melanogaster: The Fruit Fly Historical view of the fly Drosophila as a model organism II. Developmental Biology Definition Historial view III. Growth Control: The different parameters Our system: the fly wing Systemic vs Organ-autonomous Growth Control Size Control and Human Disease

  3. I. Genetics

  4. Genetics is a discipline of biology, is the science of genes, heredity, and variation in living organisms Genetics deals with the molecular structure and function of genes, gene behavior in the context of a cell or organism, patterns of inheritance from parent to offspring, and gene distribution, variation and change in populations GENETICS + ORGANISM EXPERIENCES = FINAL OUTCOME

  5. Mendelian and Classic Genetics Gregor Mendel (1822 - 1884) studied the nature of inheritance in plants observed that organisms inherit traits by way of discrete units of inheritance, which are now called genes traced the inheritance patterns of certain traits in plants and described them mathematically

  6. Discrete Inheritance and Mendel’s Laws studied the segregation of heritable traits in pea plants 29,000 pea plants Grow easily, develop pure-bred strains, and control their pollination Pisumsativum

  7. Discrete Inheritance and Mendel’s Laws

  8. Discrete Inheritance and Mendel’s Laws Dominanttrait Alleles: is one of a number of alternative forms of the same gene

  9. Discrete Inheritance and Mendel’s Laws

  10. Discrete Inheritance and Mendel’s Laws 3:1 ratio diploidspecies: each individual has two copies of each gene, one inherited from each parent organisms with two copies of the same allele of a given gene are called homozygous organisms with two different alleles of a given gene are called heterozygous

  11. Discrete Inheritance and Mendel’s Laws homozygous heterozygous homozygous (WW) Purple (Ww) Purple (ww) White

  12. Discrete Inheritance and Mendel’s Laws homozygous heterozygous homozygous (WW) Purple (Ww) Purple (ww) White Genotype (set of alleles) Phenotype (observable traits) W W one allele is called dominant other allele is called recessive

  13. Discrete Inheritance and Mendel’s Laws

  14. Discrete Inheritance and Mendel’s Laws

  15. Discrete Inheritance and Mendel’s Laws 3:1 ratio

  16. Discrete Inheritance and Mendel’s Laws

  17. Discrete Inheritance and Mendel’s Laws 1 The Law of Dominance: In a cross between contrasting homozygous individuals, only one form of the trait will appear in the F1 generation - this trait is the dominant trait

  18. Discrete Inheritance and Mendel’s Laws 1 The Law of Dominance: In a cross between contrasting homozygous individuals, only one form of the trait will appear in the F1 generation - this trait is the dominant trait 2 The Law of Segregation: when any individual produces gametes, the copies of a gene separate so that each gamete receives only one copy (allele) - a gamete will receive one allele or the other

  19. Discrete Inheritance and Mendel’s Laws 1 The Law of Dominance: In a cross between contrasting homozygous individuals, only one form of the trait will appear in the F1 generation - this trait is the dominant trait 2 The Law of Segregation: when any individual produces gametes, the copies of a gene separate so that each gamete receives only one copy (allele) - a gamete will receive one allele or the other 3 The Law of Independent Assortment: alleles responsible for different traits are distributed to gametes (and thus the offspring) independently of each other

  20. Drosophila melanogaster

  21. Drosophila melanogaster: the fruit fly

  22. Drosophila melanogaster: the fruit fly

  23. Historical view of Drosophila Charles W. Woodworth (1865 - 1940) 1900 – First to breed Drosophila in the Lab

  24. Historical view of Drosophila Thomas Hunt Morgan (1866 - 1945) 1900 – Started to work with Drosophila (study of mutation) 1910 – First mutation was found (white) 1911 – Genes are on chromosomes 1933 – Nobel Prize in Physiology or Medicine for the role played by chromosomes in heredity

  25. Historical view of Drosophila

  26. Historical view of Drosophila Hermann Joseph Müller (1890 - 1967) 1946 – Nobel Prize in Physiology or Medicine for the discovery of the genetics effects of Radiation (X-ray mutagenesis)

  27. Historical view of Drosophila Eric Wieschaus (1947 - ) JanniNusslein-Volhard (1942 - ) Edward B. Lewis (1918 - 2004) 1995 – Nobel Prize in Physiology or Medicine for revealing the genetic control of embryonic development

  28. Historical view of Drosophila Jules A. Hoffmann (1941 - ) Bruce A. Beutler (1957 - ) Ralph M. Steinman (1943 – 2011) 2011 – Nobel Prize in Physiology or Medicine for the discovery of the dendritic cell and its role in adaptive immunity

  29. Why Drosophila melanogaster is such a good model organism ?

  30. Why Drosophila melanogaster is such a good model organism ? Short Life Cycle (Temperature Dependent – 10 days @ 25ºC) Each Female lays 400-500 eggs Easy to maintain in the Lab (low cost) Suitable of Genetic Manipulation Extensive set of genetic tools available Simple karyotype: 4 pairs of chromosomes (3 autosomes + sexual chromosomes) Gene Sequence Conservation with humans: 60% Functional conservation of regulatory and biochemical pathways with humans

  31. Why Drosophila melanogaster is such a good model organism ? Short Life Cycle (Temperature Dependent – 10 days @ 25ºC) Each Female lays 400-500 eggs Easy to maintain and manipulate in the Lab (low cost) Suitable of Genetic Manipulation Extensive set of genetic tools available Simple karyotype: 4 pairs of chromosomes (3 autosomes + sexual chromosomes) Gene Sequence Conservation with humans: 60% Functional conservation of regulatory and biochemical pathways with humans

  32. Why Drosophila melanogaster is such a good model organism ? Short Life Cycle (Temperature Dependent – 10 days @ 25ºC) Each Female lays 400-500 eggs Easy to maintain and manipulate in the Lab (low cost) Suitable of Genetic Manipulation Extensive set of genetic tools available Simple karyotype: 4 pairs of chromosomes (3 autosomes + sexual chromosomes) Gene Sequence Conservation with humans: 60% Functional conservation of regulatory and biochemical pathways with humans

  33. Why Drosophila melanogaster is such a good model organism ? Short Life Cycle (Temperature Dependent – 10 days @ 25ºC) Each Female lays 400-500 eggs Easy to maintain and manipulate in the Lab (low cost) Suitable of Genetic Manipulation Extensive set of genetic tools available Simple karyotype: 4 pairs of chromosomes (3 autosomes + sexual chromosomes) Gene Sequence Conservation with humans: 60% Functional conservation of regulatory and biochemical pathways with humans

  34. Why Drosophila melanogaster is such a good model organism ? Short Life Cycle (Temperature Dependent – 10 days @ 25ºC) Each Female lays 400-500 eggs Easy to maintain and manipulate in the Lab (low cost) Suitable of Genetic Manipulation Extensive set of genetic tools available Simple karyotype: 4 pairs of large chromosomes (3 autosomes + sexual chromosomes) Gene Sequence Conservation with humans: 60% Functional conservation of regulatory and biochemical pathways with humans

  35. Why Drosophila melanogaster is such a good model organism ? Short Life Cycle (Temperature Dependent – 10 days @ 25ºC) Each Female lays 400-500 eggs Easy to maintain and manipulate in the Lab (low cost) Suitable of Genetic Manipulation Extensive set of genetic tools available Simple karyotype: 4 pairs of large chromosomes (3 autosomes + sexual chromosomes) Gene Sequence Conservation with humans: 60% Functional conservation of regulatory and biochemical pathways with humans

  36. Why Drosophila melanogaster is such a good model organism ?

  37. Drosophila melanogaster Life Cycle Growth Phase

  38. Drosophilamelanogaster: whyissuch a potentgeneticorganism ? Genome fully sequenced Mutant animals are readily obtainable Huge amount of transgenic lines available Targeting gene expression in a temporal and spatial fashion

  39. Targeting gene expression: Gal4-UAS System Driver line Responder line Big collection of both Driver and Responder Lines available Temperature Dependence of the Driver Line

  40. Targeting gene expression: Gal4-UAS System

  41. Targeting gene expression: Gal4-UAS System

  42. II. Developmental Biology

  43. Developmental Biology

  44. Historical Perspective – The first steps Aristotle (384 – 322 AC) Study of the Development of the chick The semen of the male provides the “form” or soul and the female the unorganized matter (menstrual blood) allowing the embryo to grow: EPIGENESIS Theory of Preformationism: organs with their own shape expand Theory of Spontaneous Generation: life of invertebrates emerges from non-living matter (“nothing”)

  45. Historical Perspective - Renaissance Leonardo da Vinci (1452 - 1519) Dissection of human corpses Drawings of the vascular and system First drawing of the human fetus in the utero Views of a Fetus in the Womb Leonardo da Vinci, ca. 1510-1512

  46. Historical Perspective - Renaissance

  47. Historical Perspective - Renaissance Antonie van Leeuwenhoek (1632 - 1723) Discoveredthemicroorganisms: animacules Discovered the spermatozoa “…now that I have discovered that the animalcules also occur in the male seed of quadrupeds, birds and fishes…, I assume with even greater certainty than before that a human being originates not from an egg but from an animalcule that is found in the male semen”

  48. Historical Perspective - Renaissance PREFORMATIONISM organisms develop from miniature versions of themselves NicolaasHartsoeker in 1695

  49. Historical Perspective - Renaissance Reiner de Graaf (1641 - 1673) Discovered the follicles of the ovary (known as Graafian follicles), in which the individual egg cells are formed Rejecting the preformationism

  50. Historical Perspective Ernst Haeckel (1834 - 1919) "ontogenyrecapitulatesphylogeny” Recapitulation Theory / Embryological Parallelism developing from embryo to adult, animals go through stages resembling or representing successive stages in the evolution of their remote ancestors

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