Caenorhabditis elegans February 11th, 2005 Princeton University Karen Li Image from http://ucdnema.ucdavis.edu/imagemap/nemmap/ENT156HTML/slides/fromWWW/cele/wbg5.1.jpg Road map for today’s talk 1. Model organisms: Uses? Advantages? 2. Bioinformatics • WormBase 3. Spectraplakins 4. Caenorhabditis Elegans (“The Worm”) 5. One scientist you should know: Sydney Brenner 6. How to maintain your worm? Model Organisms Model systems Advantages Uses Amphibians (Xenopus) large eggs, easy to obtain and fertilize eggs develop externally fragment culture embryology, induction RNA and protein localization morphogenesis cell cycle Drosophila genetics, gene cloning short generation time axis formation segmentation and cell identity signalling pathways Nematode genetics transparent embryo small number of cells, invariant lineages organelle movement cell fate decisions signal transduction Zebrafish transparent eggs genetics Mouse mammal with relatively short generation time genetics organogenesis segmentation cell determination Chicken embryos similar to mammals easier to obtain and observe embryo culture organogenesis cell death ALSO: Sea urchins, ascidians, amphioxus, plants Slide from Cellular and Developmental Biology lecture RNA and protein localization morphogenesis cell determination Heredity information in the egg cell determines the nature of the whole multicellular organism. Sea urchin Mouse Fucus seaweed Heredity information determines how structures in the early stages of the organism or a part of the organism develop. This process is called morphogenesis. Homologous organs (common ancestor) and Analogous organs Effect of mutation in the kit gene: Both the baby and mouse are heterozygous for the kit gene. This causes defective pigmentation because pigment cells depend on the kit product as a receptor. th Bioinformatics Bioinformatics: the systematic development and application of computing systems and computational solution techniques to the analysis of biological data obtained by experiments, modeling, database search, and instrumentation DATABASES •NCBI (National Center for Biotechnology Information)—NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information - all for the better understanding of molecular processes affecting human health and disease. www.ncbi.org •WormBase – rapidly evolving model organism database for the biology and genomics of Caenorhabditis elegans and Caenorhabditis briggsae www.wormbase.org BLAST (Basic Local Alignment Search Tool)—search tool designed to take protein and nucleic acid sequences and compare them against a selection of NCBI databases. This gives information about direct relationships that share isolated regions of similarity. Tutorial: http://www.geospiza.com/outreach/BLAST/index.html Spectraplakins! Spectraplakins are large proteins that bind to all three components of the cytoskeleton (actin, tubulin, and intermediate filaments). They are required for mechanical resilience of the epidermis. In Drosophila, spectraplakins are involved in crosslinking cytoskeletal filaments, linking the cytoskeleton to the plasma membrane proteins, and acting as a scaffold protein that recruits signaling proteins to sites of cytoskeletal activity Figure from Journal of Cell Science 115, 4215-4225 (2002) Caenorhabditis elegans (Caeno, recent; rhabditis, rod; elegans, nice), is a free-living, parasitic nematode that lives in soil, across most of the temperate regions of the world, where it survives by feeding on microbes such as bacteria. Image from http://elegans.swmed.edu/Pictures/wild-type_low.gif Video Links Bird’s Eye view: http://www.wormatlas.org/handbook/fig.s/BIRDSEYEMOVIE.qt Worm crawling: http://www.bio.unc.edu/faculty/goldstein/lab/crawl.mov Professor Sydney Brenner In 2002, the Nobel Assembly at Karolinska Institutet awarded the Nobel Prize in Physiology or Medicine jointly to Sydney Brenner, Robert Horvitz and John Sulston for their discoveries concerning "genetic regulation of organ development and programmed cell death". By using the nematode Caenorhabditis elegans as a model system, the Laureates identified key genes regulating these processes. They have also shown that corresponding genes exist in higher species, including man. http://nobelprize.org/medicine/educational/poster/2002/index.html; Brenner image from http://elegans.swmed.edu/Pictures/People/Brenner.gif Life cycle of C. elegans: The life cycle is temperature-dependent. C. elegans goes through a reproductive life cycle (egg to egg-laying parent) in 5.5 days at 15°C, 3.5 days at 20°C, and 2.5 days at 25°C. http://avery.rutgers.edu/WSSP/StudentScholars/project/introduction/worms.html Dauer stage: when a worm encounters shortage of food, it enters the developmental pathway to form the dauer larva that can survive for months without food. Male and Hermaphrodite Worms Figure 1. Photomicrographs showing major anatomical features of the C. elegans adult hermaphrodite (top) and male (bottom). Shown are lateral views under bright-field illumination. Bar, 20 μm. (Reprinted, with permission, from Sulston and Horvitz 1977.) Hermaphrodite Images from http://www.wormatlas.org/handbook/bodyshape.htm Male Image from http://www.wormatlas.org/handbook/bodyshape.htm Inside the mouth of a male worm Image from http://www.wormatlas.org/maleHandbook/GenIntroMalePartI.htm Helpful links Hypodermis: http://www.wormatlas.org/handbook/hypodermis/hypodermis.htm Mating: http://www.wormatlas.org/maleHandbook/figsMale/WAmating.mov Worm eating: http://www.mcb.arizona.edu/wardlab/eatingvid.html How to transfer your worms Image from http://ucdnema.ucdavis.edu/imagemap/nemmap/ENT156HTML/slides/fromWWW/cele/wbg8.2.jpg Intracellular Signaling Cascades in C. elegans Vulval Induction http://nema.cap.ed.ac.uk/teaching/devbio3/NVD_lecture.html