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?

ABCDEFG

Chemical signals are converted from one type of signalinto another to elicit a molecular response from the organism.All organisms require signaling pathways to live.

Letters represent chemicals or proteins. Arrows representenzymatic 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

http://www.celanphy.sci.kun.nl/Bruce%20web/Flash%20Movies.htm

Database to deal with signaling pathways (still in development)

http://www.grt.kyushu-u.ac.jp/spad/index.html

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).

Databases of KEGG

Metabolic pathways http://www.genome.ad.jp/kegg/kegg2.html - pathway

Regulatory pathways

Ortholog tables

Other Signaling Pathway Links

http://david.niaid.nih.gov/david/Links-Pathways.htm

http://sugp.caltech.edu/endomes/

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 BioinformaticsLiterature SearchingNCBI ModelScoring MatricesDynamic ProgrammingGlobal vs. Local Sequence AlignmentMultiple Sequence AlignmentPhylogenetic TreesMolecular Life Science DatabasesProtein ModelingMicroarraysProteomics

EthicsPrivacySecurityHuman Genome

MolecularLife Science

Central DogmaMolecular Basis of DiseaseDNA Primary SequenceProtein Primary, Secondary, Tertiary StructureMolecular EvolutionSignal Transduction

Computer ScienceStructured ProgrammingData StructuresAlgorithmsComplexity AnalysisSoftware Engineering

StatisticsProbability TheoryHidden Markov ChainBayes’ TheoryExpect ValueRule of Counting

Course SummaryProgram Learning Objectives (partial list):

Retrieve gene sequence information from GenBank and Protein databasesUse BLAST program to conduct gene similarity searchesAlign multiple sequences with Clustal W programPredict protein functional motifs with BLIMPs Display and compare 3-D structures of proteinsModel 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 alignmentsUnderstand 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

PubMedDotterNeedleman-Wunsch global alignmentSmith-Waterman local alignmentBLASTFASTAPhylipMascot/ProteinProspector

ChouFasmanKyte-DoolittleGORCLUSTAL WBLIMPsPSIPREDDeepView (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 proteinsModular nature of proteinsSliding windowAlignment methods (Local vs. Global)Dynamic programmingStatistics (E-value, Z-score, Probabilities, Bayes’ Theorem)

Concepts in bioinformatics II

Primary and secondary databasesSimilarity vs. identical amino acidsScoring matrices (PAM, BLOSUM, PSSM)Multiple alignmentGuide treesNeural networksProtein structure predictionDeveloping 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 Inform-a newsletter for bioinformaticists

Systems Biology