Presentation is loading. Please wait.

Presentation is loading. Please wait.

Flies as a model for the study of human disease Rapid forward genetics – isolate mutants through transposons or chemical mutagenesis Rapid forward genetics.

Similar presentations


Presentation on theme: "Flies as a model for the study of human disease Rapid forward genetics – isolate mutants through transposons or chemical mutagenesis Rapid forward genetics."— Presentation transcript:

1 Flies as a model for the study of human disease Rapid forward genetics – isolate mutants through transposons or chemical mutagenesis Rapid forward genetics – isolate mutants through transposons or chemical mutagenesis Rapid construction of transgenic models of human disease Rapid construction of transgenic models of human disease Well established easy systems to drive knockdown/knockout or over expression of gene expression in tissue or temporal specific patterns Well established easy systems to drive knockdown/knockout or over expression of gene expression in tissue or temporal specific patterns Rapid determination of the molecular basis of disease mechanisms Rapid determination of the molecular basis of disease mechanisms Able to rapidly identify modifier/bypass gene pathways via genetic screens for enhancers or suppressors of phenotypes Able to rapidly identify modifier/bypass gene pathways via genetic screens for enhancers or suppressors of phenotypes Easy to culture cell lines – very-easy to dsRNA treat genes of interest

2 GAL4 Tissue specific promoter X Transgene UAS OFF ON The progeny of this mating will express the transgene in cells also expressing GAL4 GAL4 is a transcriptional activator protein from yeast The upstream activating sequence is the GAL4 target GAL4 Tissue specific promoter Transgene UAS The fly GAL4/UAS binary transgenic expression system

3 Egg L1 Larva (juvenile) L2 L3 White (early) pupa Pupa Adult 24 hrs The life cycle of a fly

4 Drosophila has 4 chromosomes H. sapiens chromosomes

5 Embryonic Brain Development Hartenstein - Atlas of Drosophila Development (1993) Cold Spring Harbour Laboratory Press

6 Larval/Pupal Brain Development Hartenstein - Atlas of Drosophila Development (1993) Cold Spring Harbour Laboratory Press

7 The fly fat body is analogues to adipose tissue, the liver and the haematopoietic system in mammals. Hotamisilgil (2006) Inflammation and metabolic disorders Nature 444,

8 Leopold & Perrimon (2007) Drosophila and the genetics of the internal milieu Nature 450, Drosophila oenocytes are analogous to mammalian hepatocytes

9 Pandley and Nichols (2011) Human Disease Models in Drosophila melanogaster and the Role of the Fly in Therapeutic Drug Discovery Pharmacological Reviews 63(2) Testing drug candidates in flies Throughput

10 ‘Humanized” fly Pex1 mutations

11

12

13 A ‘visible’ screen for peroxisome function in Drosophila eyes ey – eyeless:GAL4 GMR– Glass Multiple Reporter:GAL4

14 Pex1 *RNAseq Drosophila Pex1 is expressed throughout development

15 Pex1 *microarray Drosophila Pex1 is expressed in multiple tissues

16 Pex3 *microarray Drosophila Pex3 is expressed in multiple tissues

17 Pex7 *microarray Drosophila Pex7 is expressed highly in the CNS

18 Drosophila Pex1

19 Genome wide analysis of Pex1 loss

20

21

22

23 Loss of Pex1 in flies causes larval lethality

24 Loss of Pex1 in flies causes a poor growth phenotype

25 Pex1 mutations do not affect fly musculature

26 Loss of Pex1 in flies causes a poor growth phenotype

27 Loss of Pex1 in flies causes severe effects on the Drosophila nervous system

28

29

30 High throughput screening dsRNA library covering 96% of the Drosophila genome High Throughput screening

31 Studying Peroxisomes in cultured fly cells

32 Acknowledgements U of Alberta Simmonds Laboratory Jing Li Julie Haskins Alana Pay Rachubinski Laboratory Jenny Chang Fred Mast Robert Tower Rick Porier Dr. Sarah Hughes McGill Univeristy Dr. Nancy Braverman


Download ppt "Flies as a model for the study of human disease Rapid forward genetics – isolate mutants through transposons or chemical mutagenesis Rapid forward genetics."

Similar presentations


Ads by Google