| M W F; 10:10 - 11:00 pm |
Molecular Biology |
Douglas W. Smith |
| York 2722 |
BIMM 100 |
5254 Muir Biology Building |
| Fall, 2000 |
x42620; dsmith@ucsd.edu |
| BIMM100 | Syllabus
| Sections / Off Hrs | Grading
Policy | DNASYSTEM
|
| Lectures | Journal
Articles | Study Qs | Lab
Techniques | Exams |
Outline:
The following includes only Lander's Ten Goals ...
The Introduction to Bioinformatics topics is not included, due to time constraints in the course ...
For those interested in a more complete Introduction to Bioinformatics, you can look at the lecture here ... however, you are NOT responsible for this additional information for the BIMM 100 Final Exam ... you are only responsible for the information found here on Lander's Ten Goals ...
A. The new "Genomics"
Eric Lander's "Ten Goals" for tools and paths of the New Genomics (Human focus):
DNA level:
1. Routine re-sequencing of megabase regions of genomic DNA
disease susceptibilities and predispositions ... sequence affected and unaffected people
cancers ... sequence tumour and normal tissue ... get genotyping
New sequencing technologies under development:
massively parallel DNA arrays ...
state of the art currently available: Perkin/Elmer ABI capillary gel sequencing system
2. Systematic identification of common variants in genes
Usually, small number of common variants per locus
Variants => clues to susceptibilities, e.g. 3 variants of apolipoprotein E in Alzheimer's
cardiovascular disease, thrombosis, heart disease, obesity, HIV resistance
Get most such variant sequences from sequences of 100 random individuals
Move from Family-based Linkage Analyses to Association Analyses:
Test disease susceptibility against ALL common variants SIMULTANEOUSLY
by genotyping a well-characterized clinical group with a comprehensive DNA array
This will be done by characterizing the SNPs
(Single Nucleotide Polymorphisms) associated with a given human
disease.
Use of DNA array technology for human SNP analysis is already
underway with the availability of the Affymetrix
GeneChip® HuSNP™ ...
an example of results for such analysis can be found here.
See below for discussion of DNA microarray technology ...
Thereby home in on Susceptibility Genes
Noncoding regions also important ... variants in regulatory regions
Population Genetics a key to Biomedical Research
3. Rapid sequencing of other organisms
Comparative Whole Genome Genomics ... details of Molecular Evolution
Sequence conservation: constraints on Proteins, key motifs
Sequence differences: diversity of form and function
Sequencing: automation, miniturization
RNA level:
4. Simultaneous Monitoring of Expression of ALL Genes
mRNA levels define State of the Cell ...
Monitor ALL mRNAs at quantitative sensitivity level of 1 molecule per cell
and a qualitative sensitivity level sufficient to distinguish alternative splicing
Use of DNA microarrays will make this possible ...
Use this information for:
1) Description: catalogs of proteins present in different cells, different stages,
different environments
2) Classification: classify proteins re susceptibilities, disease, population subtypes
3) Circuitry ...Genetic Networks ... gene expression circuits for development, response pathways
5. Generic Tools for Manipulating Cell Circuitry
Need to: Disrupt and Manipulate gene expression ... Arsenal of new Tools en route:
Deletion Mutant for every Gene ... already
being done for Yeast;
see Web site here
Characterization of Null Mutant ... Plus: Screens for Suppressors, Enhancers, etc
Will become characteristic Molecular Biology of Yeast, Worms, Flies
Will reveal all basic Eukaryotic functions, Genetic Networks, Response Pathways
High Throughput tools ... Many analyses simultaneously
Minaturization, both in size (grids) and volumes (nanoliter reactions)
=> greatly reduced time (hours -> minutes or seconds)
Automation: Gridding technologies via robots ...
Protein Knockout Reagents ...
combinatorial libraries: small molecule inhibitors - Aptamers
Protein Level - Proteome: all Proteins encoded by Genome
6. Monitoring Level and Modification State of ALL Proteins
Equally important to monitoring all mRNAs ... PLUS:
Post-translational and Genetic Network modifications, eg. Phosphorylation State
Need new Tools to do this ... Possibilities:
2D Protein gel analyses of proteins, followed by Mass Spec analysis
Mass Spectrometry analyses of peptide fragments ... Protein "signatures"
Grid array technologies
7. Systematic Catalogs of Protein Interactions:
Genetic Networks - cascades of reactions ...
Macromolecular Complexes
Need new Tools ... Yeast "Two Hybrid" System a beginning
Catalogs: ... comprehensive Interaction Maps of Genomes and their Proteins
Done already for bacteriophage T7: 55
proteins ...
Genome sequence, proteins, protein interactions ... all now known
Also need Principles for discerning Pathways and Networks without first knowing the Protein interactions ...
8. Identification of All Basic Protein Shapes:
Most probably, limited number of Protein Shapes; limited number of Protein Families
Analyse amino acid sequences against Database of Protein Shapes
Some of this is already being done; see the databases at:
Pfam - protein multiple sequence alignments and common protein domains
SCOP - Structural Classification of Proteins
CATH - protein classification by Class, Architecture, Topology, and Homology
Society Level:
9. More Attention to Ethical, Legal and Social Issues (ELSI)
Intrusion issues ... patent issues ...
Safeguards: concerns for Individuals and for Society
10. Public Education
School children ... general public ... physicians ... genetic counselors
| BIMM100 | Syllabus
| Sections / Off Hrs | Grading
Policy | DNASYSTEM
|
| Lectures | Journal
Articles | Study Qs | Lab
Techniques | Exams |
If you have problems or comments, send email to Doug
Smith
