Presentation is loading. Please wait.

Presentation is loading. Please wait.

NANOG The secret to immortality Ka Yi, Ling Genetics 677 04/28/09.

Similar presentations


Presentation on theme: "NANOG The secret to immortality Ka Yi, Ling Genetics 677 04/28/09."— Presentation transcript:

1 NANOG The secret to immortality Ka Yi, Ling Genetics 677 04/28/09

2 Overview Pluripotency All about Nanog Gene decoding Protein translation Nanog web Future directions Image from http://www.cartoonstock.com/newscarto ons/cartoonists/ato/lowres/aton305l.jpg

3 Star of immortality Image obtained from Takahashi et al. (2007), Image obtained fromTakahashi et al. (2007) DOI 10.1016/j.cell.2007.11.019 and Lensch M. W. & Sullivan S. The cycle of developmental potency. Abcam(2008)

4 What’s the Nanog deal? 1)Pluripotent marker 2)Reprogramming factor Image from: http://www.savagechickens.com/images/chickengoal.jpghttp://www.savagechickens.com/images/chickengoal.jpg

5 Deciphering Nanog Image obtained fromHyslop et al. (2005) Stem Cells 2005;23:1035–1043, NCBI MMDB, http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=61857 and Lensch M. W. & Sullivan S. The cycle of developmental potency. Abcam(2008)

6 What is pluripotency?

7 Pluripotency Pluripotent Multi- potent

8 PotencyPotencyPotencyPotency Eg. ES cells, iPS cells Eg. Adult stem cells

9 Forever Young Image obtained from http://ific.uv.es/~lopes/pictures/kukuxumusu.jpg

10 Modified from http://www.csa.com/discoveryguides/stemcell/images/pluri.jpg The Promise of Stem Cell Research Understanding Developmental Biology Regenerative Medicine Drug development

11 How to induce pluripotent cells Figure from: http://graphics8.nytimes.com/images/2007/06/06/science/0607-nat-webCELL.gif Nanog Sox2 Oct4 Lin28

12 Necessary but not Sufficient Image obtained fromTakahashi (2007) DOI 10.1016/j.cell.2007.11.019

13 Goal: To learn the mechanisms of Nanog function Nanog Image modified from http://i1.iofferphoto.com/img/item/489/760/11/discover_how_stuff_works.jpg

14 Learning lessons Image from http://www.chrismadden.co.uk/genetics/dna-music.gif

15 Nanog signaling Image from Applied Biosystems Gene Assist Pathway systems, http://www.ambion.com/tools/pathway/pathway.php?pathway=Nanog%20in%20Mammalian%20ESC%20Pluripotency

16 Multi-ome approach Image from: http://innovech.files.wordpress.com/2007/11/genome3.jpg DNA Messenger RNA Protein Genome Transcriptome Proteome

17 Image modified from Stein (2001) and the Human Proteome Initiative. (2007) http://ca.expasy.org/sprot/hpi/hpi_desc.html Retrieved March 24, 2009. and courtesy of Eva and Jessica’s Gen677 presentation

18 Fitting the pieces Figure from http://www.ittc.ku.edu/bioinfo_seminar/images/wheel.gif

19 Chromosome hunting GeneID: 79923 Size: 6661 base pairs Chromosome: 12 Location: 12p13.31 Image obtained from GeneCards, http://www.genecards.org/cgi-bin/carddisp.pl?gene=NANOG&search=Nanoglhttp://www.genecards.org/cgi-bin/carddisp.pl?gene=NANOG&search=Nanogl

20 DNA motifs What: Sex-determining region Y gene product (SRY) Consensus: AAACWAM Number of hits (Score above 99): 6 What: Homeo domain factor (Nkx-2.5/Csx), tinman homolog Consensus: TYAAGTG Number of hits (Score above 99): 7 Image obtained from Kyoto University Bioinformatics Centre, http://motif.genome.jp/http://motif.genome.jp/

21 DNA motifs What: CAP signal, transcription initiation Consensus: NCANNNNN Number of hits (Score above 99): 2 What: GATA binding factor-1 Consensus: SNNGATNNNN Number of hits (Score above 99): - (Score above 90): 12 Image obtained from Kyoto University Bioinformatics Centre, http://motif.genome.jp/http://motif.genome.jp/

22 Nanog: DNA level Image from Applied Biosystems Gene Assist Pathway systems, http://www.ambion.com/tools/pathway/pathway.php?pathway=Nanog%20in%20Mammalian%20ESC%20Pluripotency

23 NANOG protein crystals Image obtained from STRING, http://string.embl.de/newstring_cgi/show_network_section.plhttp://string.embl.de/newstring_cgi/show_network_section.pl FASTA number: NP_079141 UniProtKB : Q9H9SO Length of protein: 305 aa Subcellular location: NucleusQ9H9SO

24 Nanog (Mus muculus) Image obtained from NCBI MMDB, http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=61857

25 Homeobox domain Pfam, SMART and prosite – similar predictions Image from Prosite, http://www.expasy.ch/cgi-bin/prosite/ScanView.cgi?scanfile=89996073962.scan.gz and NCBI conserved domains, http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cl00084http://www.expasy.ch/cgi-bin/prosite/ScanView.cgi?scanfile=89996073962.scan.gzhttp://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cl00084

26 Nanog signaling Image from Applied Biosystems Gene Assist Pathway systems, http://www.ambion.com/tools/pathway/pathway.php?pathway=Nanog%20in%20Mammalian%20ESC%20Pluripotency

27 How does Nanog work?

28 Phosphorylation Image obtained from NetPhos 2.0 Server, http://www.cbs.dtu.dk/cgi-bin/nph-webface?jobid=netphos,49DE647502FAC760&opt=none

29 Dimerization

30 Drawing analogies

31 Animal stars Image from: http://www.socialfiction.org/img/Enlarged_c_elegans.PNG, http://brembs.net/learning/drosophila/fly_down.jpg, http://64.207.144.142/movabletype/PETA2Daily/archives/kick1.PNG and http://images.forbes.com/images/2001/07/26/mice_400x300.jpghttp://www.socialfiction.org/img/Enlarged_c_elegans.PNG http://brembs.net/learning/drosophila/fly_down.jpghttp://64.207.144.142/movabletype/PETA2Daily/archives/kick1.PNG

32 Nanog in other organisms Image obtained from NCBI Homologene, http://www.ncbi.nlm.nih.gov/sites/entrez

33 Phylogeny tree – Closeness of Nanog Image from Deereeper A. et al. Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W465-9. Epub 2008 Apr 19. (PubMed)

34 TreeFAM relations Image from Treefamilies database, http://www.treefam.org/cgi-bin/TFinfo.pl?ac=TF337402

35 Comparing NANOG orthologues Homo sapiensMus muculus Image from STRING, http://string.embl.de/newstring_cgi/show_network_section.pl http://string.embl.de/newstring_cgi/show_network_section.pl

36 Protein friends of Nanog Table obtained from Lewitzky. M and Yamanaka S. (2007) Reprogramming somatic cells towards pluripotency by defined factors. Current Opinion in Biotechnology. 18: 467-473

37 Nanog Paralogues Image obtained from GeneCard, http://www.genecards.org/cgi-bin/cardsearch.pl#results

38 Mutant phenotypes Jaenisch paper Table obtained from Boyer, L. A., Mathur, D. and Jaenisch R. (2006) Molecular control of pluripotency. Current Opinion in Genetics & Development. 16, 455-462

39 Nanog: protein level Image from Applied Biosystems Gene Assist Pathway systems, http://www.ambion.com/tools/pathway/pathway.php?pathway=Nanog%20in%20Mammalian%20ESC%20Pluripotency

40 Pseudo Nanog related to cancer?

41 Inside view of crazy NANOG Image taken from Siu et al.(2008) DOI: 10.2353/ajpath.2008.080288

42 Inside view of looney NANOG Image taken from Introduction to Reproductive Biology. http://www.sgul.ac.uk/depts/immunology/~dash/troph/trophoblast.jpg http://www.sgul.ac.uk/depts/immunology/~dash/troph/trophoblast.jpg

43 NANOG gone looney Image from SonoWorld (2009) Complete Molar Gestation: Role of Ultrasound, http://www.sonoworld.com/Article/ShowArticleImage.aspx?id=9098&Type=Paragraph and Mchumor, http://www.pioneer.net/~mchumor/00images/2192_pregnancy_cartoon.gif http://www.sonoworld.com/Article/ShowArticleImage.aspx?id=9098&Type=Paragraphhttp://www.pioneer.net/~mchumor/00images/2192_pregnancy_cartoon.gif

44 Moving on Image from http://grandtextauto.org/archives/newyorker.jpg

45 Image modified from Stein (2001) and the Human Proteome Initiative. (2007) http://ca.expasy.org/sprot/hpi/hpi_desc.html Retrieved March 24, 2009. and courtesy of Eva and Jessica’s Gen677 presentation

46 Fitting the pieces Figure from http://www.ittc.ku.edu/bioinfo_seminar/images/wheel.gif

47 GTD detection Image from http://www.mchumor.com/00images/6575_biology_cartoon.gif

48 Confirmation assays Function analysis Nanog dimer Phosphorylation Global outlook Chemical genetics Transcriptome sequencing Reprogramming Image modified from http://dcad.com.pl/image/dna1.jpg, http://www.dnastar.com/media/linegraphLrg.jpg and http://www.cs.usyd.edu.au/%7Eirena/arrayimage.jpghttp://dcad.com.pl/image/dna1.jpghttp://www.dnastar.com/media/linegraphLrg.jpg http://www.cs.usyd.edu.au/%7Eirena/arrayimage.jpg

49 Cures for tomorrow Image from: http://gen677.weebly.com/uploads/8/6/5/7/865764/28942.jpg

50 Acknowledgements Thank you:Ahna for her kind help and guidance; Genetics 677 for the kind peer feedbacks andJamie for the inspirational research!

51 Thank you! Any questions? Image from http://www.newslettercartoons.com/freedaily/5651_todayT.gif and http://www.media-freaks.com/work/leilei/peterpan/peterpan-02.jpghttp://www.newslettercartoons.com/freedaily/5651_todayT.gif http://www.media-freaks.com/work/leilei/peterpan/peterpan-02.jpg


Download ppt "NANOG The secret to immortality Ka Yi, Ling Genetics 677 04/28/09."

Similar presentations


Ads by Google