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Group Members: Wayne Christopher, Ph.D. Bob Edgar, Ph.D. Duncan Brown Dan Holliman

UC Berkeley Phylogenomics Kimmen Sj ö lander http://phylogenomics.berkeley.edu kimmen@uclink.berkeley.edu Algorithm & tool development for protein structure-function prediction. Investigation of innate immunity in plants and animals: Brian Staskawicz (Plant & Microbial Biology)

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Group Members: Wayne Christopher, Ph.D. Bob Edgar, Ph.D. Duncan Brown Dan Holliman

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  1. UC Berkeley PhylogenomicsKimmen Sjölanderhttp://phylogenomics.berkeley.edukimmen@uclink.berkeley.eduAlgorithm & tool development for protein structure-function prediction. Investigation of innate immunity in plants and animals:Brian Staskawicz (Plant & Microbial Biology) Barbara Baker (Plant & Microbial Biology) Richard Michelmore (UCDavis) Dan Portnoy (MCB) Jonathan DG Jones, Sainsbury Laboratory (UK) Thanks to the National Science Foundation for continued support Group Members: Wayne Christopher, Ph.D. Bob Edgar, Ph.D. Duncan Brown Dan Holliman And a number of talented undergrads: Jenny Liu, Jason Chan, Eric Roller, Joey Davis, Michael Jurka, Sonia Wu

  2. Engineering Mathematics Biology Chemistry & Pharmacology Ethics & Law Computer Science Genomics / bioinformatics /computational biology

  3. Algorithm development • Protein fold prediction and homolog identification • Phylogenetic inference • Structure-function analysis and prediction • Predict structural motifs conferring functional specificity • Effects of allelic variation on protein function/structure • Identify structural domains • Pathway dissection, using prediction of protein-protein (and other inter-molecular) interactions BioE 144: “Intro to Protein Informatics”

  4. Antimicrobial Protein 1 Common horse chestnut What is remote homolog detection? 1BK8 1MYN Drosomycin, Antifungal protein Fruit Fly 22% Pairwise identity

  5. Homolog recognition in the Twilight ZoneCASP2 Target T0031 1TRY TRYPSIN Fusarium Oxysporum (Fungus) EXFOLIATIVE TOXIN A Staphylococcus aureus (Bacteria) 16% pairwise identity

  6. Predicting key positions in proteins Src homology 2 (SH2) domain

  7. Panther Molecular Function Classification of the Human Genome

  8. The Universal Protein Library (UPL) U.S. Patent No. 6,128,587 Bayesian Evolutionary Tree Estimation (BETE): U.S. Patent No. 6,128,587

  9. Subfamilies found by BETE; Tree displayed at subfamily level. Trees as predictive models

  10. Berkeley Phylogenomics Group user interface

  11. Hypothesis-driven vsHypothesis-generating approaches

  12. ATale of Two DomainsHidden Markov models, Potassium channels,and excursions in the Twilight Zone

  13. Common domains are found in proteins of diverse function and structure ZA70_human (tyrosine-protein kinase) Nck_human (adapter protein) (PFAM domain identification shown)

  14. Domain analysis of Voltage-gated K+ channels HMM positions

  15. There’s a connection...

  16. Predictions: • Structure of TNF-alpha induced protein B12 is homologous to K+ channel tetramerization domain • TNF-alpha affects K+ current by • inducing protein B12, which • interacts with the K+ channel at tetramerization domain. 1T1DA Tetramerization Domain of K+ channels

  17. Investigation into innate immunity Brian Staskawicz (Plant & Microbial Biology) Barbara Baker (Plant & Microbial Biology) Richard Michelmore (UCDavis) Dan Portnoy (MCB) Jonathan DG Jones, Sainsbury Laboratory (UK)

  18. Plant and Animal Innate Immunity Mediated by Related Proteins Cytoplasmic Toll Interleukin 1 Receptor (TIR) domain

  19. 1CN2 Defensin-related proteins Toxin 2 Mexican scorpion (Na+ channel inhibitor) 1BK8 Antimicrobial Protein 1 Common horse chestnut 1ICA 1MYN Insect Defensin A Antibacterial protein Flesh Fly Drosomycin, Antifungal protein Fruit Fly

  20. Gordon Research Conference on Bioinformatics 24-29 Aug 2003 Oxford University www.grc.org

  21. UC Berkeley Phylogenomics Group Members: Wayne Christopher, Ph.D. Bob Edgar, Ph.D. Duncan Brown Dan Holliman And a number of talented undergrads: Jenny Liu, Jason Chan, Eric Roller, Joey Davis, Michael Jurka, Sonia Wu Investigation of innate immunity in plants and animals:Brian Staskawicz (Plant & Microbial Biology) Barbara Baker (Plant & Microbial Biology) Richard Michelmore (UCDavis) Dan Portnoy (MCB) Jonathan DG Jones, Sainsbury Laboratory (UK) Thanks to the National Science Foundation kimmen@uclink.berkeley.edu http://phylogenomics.berkeley.edu

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