Drosophila as a model for biological investigations

Transcription

1 Drosophila as a model for biological investigations Joanna C. Chiu Ph.D. Department of Entomology & Nematology University of California Davis, U.S.A. XXVII CBE and X CLAE Gramado, Brazil September 3, 2018

2 Outline Initial choice as a model for genetic investigations - advantages Seminal work in Drosophila Other selected examples - Drosophila spp still a good model

3 Drosophila melanogaster has the longest history of any model organism Developmental Biology (S. F. Gilbert)

4 Fly room Thomas Hunt Morgan He turned to Drosophila melanogaster to study inheritance of

5 Patrizia Romani: pic.twitter.com/wmnsavc7tc Advantages Small size Easy to rear (simple food) Short Life Cycle Fertile all year Lots of Progenies Relative cheap to maintain Easy to distinguish sexes Embryonic development outside body (easy observations) Polytene chromosome for cytogenetic maps (visual appearance/banding patterns)

6 Polytene chromosomes: endoreplication (replication in the absence of mitosis) Polytene chromosomes first observed in midges by Balbiani in the 19 th century, but put to good use in D. Melanogaster for genetic studies

7 Documenting Polytene chromosomes in larval salivary glands Bridges, C.B. (1935). Salivary chromosome maps with a key to the banding of the chromosomes of Drosophila melanogaster. J. Hered. 26: ** This work was conducted using light microscopy!

8 Early Utility of Polytene Chromosomes A small section of Bridges Polytene Map Detailed mapping of chromosome rearrangements Inferring phylogenies, species ID, and detecting genetic diversity by comparisons of banding patterns Early understanding of gene expression (chromosome puff The Ashburner model) Early days of molecular genetics physical mapping of genes by in situ and linkage analysis

9 Nobel prizes awarded to Drosophila researchers

10 1933 Nobel Prize in Physiology and Medicine Found white-eyed flies through spontaneous mutation, and concluded that the trait is sex-lin Thomas H. Morgan Discovered the role of chromosomes in heredity

11 1946 Nobel Prize in Physiology and Medicine Generated more than 100 mutants by X-ray in a few weeks more than the number of mutants discovered in the previous 50 years Hermann J. Muller Production of mutations by means of X-ray irradiation

12 1995 Nobel Prize in Physiology and Medicine Edward B. Lewis Body Plan Lewis, E.B. (1978) A Gene Complex Controlling Segmentation in Drosophila. Nature 276, Christiane Nüsslein- Volhard Embryogenesis Eric F. Wieschaus Nüsslein-Volhard, C., Wieschaus, E. (1980). Mutations Affecting Segment Number and Polarity in Drosophila. Nature 287, Awarded for their discoveries concerning the genetics cont early embryonic development

13 Identification of genes involved in Embryonic Anterior-Posterior Pattern Formation

14 Genetic control of body segments : Homeotic Genes

15 2004 Nobel Prize in Physiology and Medicine Richard Axel Discovery of odorant receptors and the organization of th olfactory system

16 2011 Nobel Prize in Physiology and Medicine Discovered Toll-like receptors and how these proteins are important for animal immune response Jules Hoffmann Awarded for his research concerning the activation of innate immunity

17 water Toll mutants do not respond well to bacterial and fungal infections fungus E. coli Figure 5. Germinating Hyphes of A.fumigatus on adead Drosophila Scanning electronmicrograph of adrosophilaadult that succumbed to infection by A. fumigatus and is covered with germinating hyphae (200 magnification). Lemaitre et al Cell 86:

18 2017 Nobel Prize in Physiology and Medicine Michael Rosbash Michael Young Jeffrey Hall Molecular mechanisms that drive our body clock

19 Drosophila as a model for studying clocks Daily rhythms of eclosion in LD and DD in different temperature C. Pittendrigh (PNAS 1954) Isolation of per mutants by examining eclosion rhythms in DD Konopka and Benzer (PNAS 1971)

20 Interlocked positive and negative transcriptional feedback loops form the core of the Drosophila molecular oscillator per clk tim PER TIM CLK Loop 1 Loop 2 CYC VRI PDP1 vri pdp1 ccgs rhythms in physiology and behavior

21 Other Selected Examples Toxicology Behavior Host-parasite interaction Models of Human Diseases and Injuries Adaptation and Evolutionary Mechanisms

22 Extensive toolkit facilitate the use of Drosophila to study insecticide resistance mechanisms Drosophila Genetics Reference Panel Lab selection using Drosophila validate validate Field populations Hales et al. (Genetics 2015)

23 nparalleled research community resources and stocks

24 Novel Behavior Assay to Study Fear in Drosophila ReVSA (Repetitive Visual Stimulus-induced Arousal) Gibson et al. Current Biology (2015) 25:1-15

25 Starved flies are more difficult to disperse (less fearful)

26 Host-parasite interactions: Drosophila has parasites too! Parasitic Wasp Leptopilina heterotoma C D Vision Neuropeptide F Kacsoh et al. (Science 2013)

27 Functional conservation between Drosophila and human genes - relevance of fly research to human health

28 Drosophila as a model for concussion and brain injury TBI = Traumatic Brain Injury Katzenberger et al. (PNAS 2013)

29 The Drosophila genus contains a wide range of species that occupy diverse habitats Great for studying genomic/molecular mechanisms underlying evolution of new traits and adaptation (new genomic resources) Rice et al. (Evol Dev 2018)

30 Limitations? Other insects might be better models for some research questions (e.g. migration) Not good as a model for some studies (complex human emotion) proper phenotypic assays may be lacking Dnmt2-only organism no substantial DNA methylation