Signaling Pathways and Summary June 30, 2005 Signaling lecture Course summary Tomorrow Next Week Friday, 7/8/05 Morning presentation of writing assignments. Evals of faculty.

What is signal transduction? Conversion of a signal from one physical or chemical form into another. In cell biology, commonly refers to the sequential process initiated by binding of an extracellular signal to a receptor and culminating in one or more specific cellular responses.

What is a signal transduction pathway? ABCDEFGABCDEFG Chemical signals are converted from one type of signal into another to elicit a molecular response from the organism. All organisms require signaling pathways to live. Letters represent chemicals or proteins. Arrows represent enzymatic steps.

What is a second messenger? An intracellular signaling molecule whose concentration increases (or decreases) in response to binding of an extracellular ligand to a cell-surface receptor.

Seven levels of regulation of cell growth

Signal Transduction Animations 0Movies.htm

Database to deal with signaling pathways (still in development)

KEGG KEGG (Kyoto Encyclopedia of Genes and Genomes) is a bioinformatics resource for understanding higher order functional meanings and utilities of the cell or the organism from its genome information. The KEGG project is undertaken in the Bioinformatics Center, Institute for Chemical Research, Kyoto University with supports from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), the Japan Society for the Promotion of Science (JSPS), and the Japan Science and Technology Corporation (JST).Bioinformatics Center, Institute for Chemical Research, Kyoto University

Databases of KEGGKEGG Metabolic pathways - pathway - pathway Regulatory pathways Ortholog tables

Other Signaling Pathway Links Pathways.htm

Goals of SoCalBSI 1)Bioinformatics software programs 2) Programming 3) Explore ethical issues 4) Future careers 5) Research experiences 6) Interactions with professional bioinformaticists 7) Foster long-lasting professional relationships

Core Bioinformatics  Literature Searching  NCBI Model  Scoring Matrices  Dynamic Programming  Global vs. Local Sequence Alignment  Multiple Sequence Alignment  Phylogenetic Trees  Molecular Life Science Databases  Protein Modeling  Microarrays  Proteomics Ethics  Privacy  Security  Human Genome Molecular Life Science  Central Dogma  Molecular Basis of Disease  DNA Primary Sequence  Protein Primary, Secondary, Tertiary Structure  Molecular Evolution  Signal Transduction Computer Science  Structured Programming  Data Structures  Algorithms  Complexity Analysis  Software Engineering Statistics  Probability Theory  Hidden Markov Chain  Bayes’ Theory  Expect Value  Rule of Counting

Course Summary Program Learning Objectives (partial list): Retrieve gene sequence information from GenBank and Protein databases Use BLAST program to conduct gene similarity searches Align multiple sequences with Clustal W program Predict protein functional motifs with BLIMPs Display and compare 3-D structures of proteins Model protein structure using a homologous structure analysis program (Deep View) Write algorithms that will perform a simple searches of gene sequences stored in a database or perform pairwise alignments Understand the statistics used in scoring aligned sequences in common programs. Appreciate the ethical issues that developed from sequencing the human genome.

List of software programs you should be familiar with PubMed Dotter Needleman-Wunsch global alignment Smith-Waterman local alignment BLAST FASTA Phylip Mascot/ProteinProspector ChouFasman Kyte-Doolittle GOR CLUSTAL W BLIMPs PSIPRED DeepView (Swiss PDB viewer)

List of databases that we studied Online Mendelian Inheritance of Man MedLine GenBank EMBL SWISSPROT Protein Information Resource ProSite BLOCKS Protein Data Bank (PDB) Swiss 2D Gel KEGG

Concepts in bioinformatics ENTREZ-Suite of connected programs that allow for analysis of genes and proteins Modular nature of proteins Sliding window Alignment methods (Local vs. Global) Dynamic programming Statistics (E-value, Z-score, Probabilities, Bayes’ Theorem)

Concepts in bioinformatics II Primary and secondary databases Similarity vs. identical amino acids Scoring matrices (PAM, BLOSUM, PSSM) Multiple alignment Guide trees Neural networks Protein structure prediction Developing software program that aligns sequences based on scoring matrices

Future of bioinformatics Traditionally divided into two camps-users and developers SoCalBSI students should have an advantage over the typical applicant to graduate school or industry position Online Journal of Bioinformatics Bio InformBio Inform-a newsletter for bioinformaticists Systems Biology