Advertisement
1 / 66

21 st Century = Biotech Century


  • 224 Views
  • Uploaded On 04-01-2011

21 st Century = Biotech Century. Completion of human genome High-throughput microarray and similar devices Cloning Genetic engineering Computational power. Everyone is moving towards Biotech. Explosive growth of biological data.

Presentation posted in : Science / Technology

Download Presentation

21 st Century = Biotech Century

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.












- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -




Presentation Transcript


21 st century biotech century l.jpg

21st Century = Biotech Century

  • Completion of human genome

  • High-throughput microarray and similar devices

  • Cloning

  • Genetic engineering

  • Computational power

Everyone is moving towards Biotech

CS 6463: An overview of Molecular Biology


Explosive growth of biological data l.jpg

Explosive growth of biological data

  • Biology is becoming more computational intensive. High throughput bioinformatics, Lots of data

    • The Molecular Biology Database Collection: 2005 update

  • Small excerpt from the A's:

    • AARSDB: Aminoacyl-tRNA synthetase sequences

    • ABCdb: ABC transporters

    • AceDB: C. elegans, S. pombe, and human sequences and genomic information

    • ACTIVITY: Functional DNA/RNA site activity

    • ALFRED: Allele frequencies and DNA polymorphisms

CS 6463: An overview of Molecular Biology


Opportunities for cs l.jpg

Opportunities for CS

  • Possibilities for CS contributions

    • Data integration problem

    • Data extraction from literature (natural language processing)

    • Database issues (including automation)

    • Visualization

    • Mining large complex data sets

CS 6463: An overview of Molecular Biology


Objective l.jpg

Objective

Basic

Introduction to basic molecular biology to computer science students by a computer scientist.

A survey of databases: NCBI, SwissProt, PDB, Transfac, …

Introduction to computational techniques in analyzing genomics (and proteomics) data

CS 6463: An overview of Molecular Biology


Communication is important l.jpg

Communication is important

CS 6463: An overview of Molecular Biology


Textbooks and course website l.jpg

Textbooks and course website

  • Required textbooks:

    • Molecular Biology of the Cell (Main text)

    • Bioinformatics, Genomics and Proteomics (Lab)

    • Other material

  • References:

    • Human Molecular Genetics (2nd Edition available for free)

    • Data Mining : Practical Machine Learning Tools and Techniques with Java Implementations (The Morgan Kaufmann Series in Data Management Systems) by Ian H. Witten, Eibe Frank (Paperback)

    • Microarrays for an Integrative Genomics (Computational Molecular Biology) [Paperback] By: Isaac S. Kohane, et al

    • Molecular Biology Web Book

  • Course website: http://www.cs.utsa.edu/~kwek/cs6463f05.html

CS 6463: An overview of Molecular Biology


Intended audience l.jpg

Intended Audience

  • CS graduate students with an interest in bioinformatics or want to explore bioinformatics. High School Biology.

  • Not for students who want to find a filler class in between classes.

  • Every Tuesday noon to 1pm, Human Genome (HuGe) lab meets to discuss current bioinformatics issues. All are welcome even if you are new to bioinformatics (but are taking this course).

CS 6463: An overview of Molecular Biology


Database search l.jpg

Database Search

CS 6463: An overview of Molecular Biology


Course organization l.jpg

Course Organization

Overview of Molecular Biology (and project discussion)

Databases

  • Introduction to Cell:

  • Cells and Genomes

  • Cell Chemistry and Biosynthesis

  • Proteins

Gene finding

Motif finding

Data preprocessing

Classification problem

Clustering problem

Microarray analysis

Basic Genetic Mechanisms

4. DNA and Chromosomes

6. From DNA to Protein

7. Control of gene expression

Sequence alignment

Hidden Markov Model

Diseases:

23. Cancer

25. Pathogens

Others: SNP, NRAi

Bioinformatics/Computational Biology

Molecular Biology

CS 6463: An overview of Molecular Biology


Project l.jpg

Project

  • Grade distributions

    • 1 Quiz – 10%

    • 2 tests – 30%

    • Homework and Lab – 10%

    • Project – 50% (+ 10% bonus)

  • Project

    • Serious in bioinformatics (all HuGe Lab members): Mini (NIH-) proposal project. Besides preliminary results, a proposal for future work (i.e. independent studies, theses). Possible collaborations with UTHSCSA and others.

      • Specific Aim(s): What do you want to do? Why is it important?

      • Background: What have been done previously? (What make you approach interesting?) Where do you get your data?

      • (Preliminary) Result: To elaborate later.

      • Future Work: To elaborate later.

    • A project: Same as above except do not need to have future work.

  • Office hours (for projects): By appointment (send me an email 24 hours before) Tu, Th 10-3, 5-7, 8:30-10. W 10:30-noon.

CS 6463: An overview of Molecular Biology


Some important dates l.jpg

Some Important Dates

  • September 13: Quiz 1 (there will be a second chance quiz)

  • September 20: Specific aim of project due. [1 meeting to discuss with me]

  • October 27: Test 1

  • October 18: Background of project due. (you must already started doing experiments) [2 meetings to discuss with me]

  • November 24: Test 2

  • December 10: Final report of project. [2 meetings to discuss with me]

  • IMPORTANT: if you do not meet me the require number of times, I am not accepting your report. Also, each meeting should be at least one week a part.

CS 6463: An overview of Molecular Biology


Your responsibility l.jpg

Your Responsibility

  • Read the assigned reading once the material is covered in lecture. Lecture is to make your reading easier.

  • Try printing out the slides to take notes.

  • Project: Observe the deadline!!!! Come and talk to me.

CS 6463: An overview of Molecular Biology


A an overview of molecular biology l.jpg

A. An overview of molecular biology

Read Human Molecular Genetic Ch. 1

A.1. Background

A.2. Macromolecules

A.3. DNA structure

A.4. RNA transcription and Gene Expression

A.5. RNA processing

A.6. Translation, post-translation processing and protein structure

A.7. Project ideas

CS 6463: An overview of Molecular Biology


Slide14 l.jpg

A.1 Background: Procaryotic and Eukaryotic Cells

  • Two types of cells:

  • Prokaryotic (bacteria)

  • Eukaryotic (multicellular organisms,

  • Ameba)

CS 6463: An overview of Molecular Biology


Slide15 l.jpg

A.1 Background: Procaryotic and Eukaryotic Cells

http://www-class.unl.edu/bios201a/spring97/group6/

CS 6463: An overview of Molecular Biology


A 2 building blocks chemical composition of eukaryotic cell l.jpg

A.2. Building Blocks: Chemical Composition of Eukaryotic Cell

  • Water [E. Coli: 70%, Mammalian Cell: 70%]

  • Macro-molecules:

    • DNA: Deoxyribonucleic Acid [E. Coli: 1%, Mammal: 0.25%]

    • RNA: Ribonucleic Acid [E. Coli: 6%, Mammal: 1.1%]

    • Proteins [E. Coli: 15%, Mammal: 18%]

  • Inorganic ions: Na+, K+, Mg+, Ca2+, Cl- [E. Coli: 1%, Mammal: 1%]

  • Lipids:

    • Phospholipids [E. Coli: 2%, Mammal: 3%]

    • Other lipids [E. Coli: -, Mammal: 0.2%]

  • Polysaccahrides [E. Coli: 1%, Mammal: 0.25%]

  • Volume: [E. Coli: 2 x 10-12cm, Mammal: 4 x 10-9cm]

  • Relative Volume: [E. Coli: Mammal = 1: 2000]

CS 6463: An overview of Molecular Biology


A 2 building blocks structure of bases nucleosides and nucleotides l.jpg

A.2 Building Blocks: Structure of bases, nucleosides and nucleotides

Purines:

DNA: ‘polymer of A, G, T, C’

RNA: ‘polymer of A, G, U (replace T), C’

Pyrimidines:

base

sugar

CS 6463: An overview of Molecular Biology


A 2 building blocks common bases found in nucleic acids l.jpg

A.2. Building Blocks: Common bases found in nucleic acids

CS 6463: An overview of Molecular Biology


A 2 building blocks 20 amino acids l.jpg

A.2 Building Blocks: 20 amino acids

Polypeptides: chains of amino acids

Carboxyl group

Amino group

CS 6463: An overview of Molecular Biology


A 2 building blocks abbreviation of amino acids l.jpg

A.2. Building Blocks: Abbreviation of Amino Acids

CS 6463: An overview of Molecular Biology


A 2 building blocks properties of amino acids i l.jpg

A.2. Building blocks: Properties of Amino Acids I

http://www.russell.embl-heidelberg.de/aas/aas.html

CS 6463: An overview of Molecular Biology


A 2 building blocks some terms for describing properties of amino acids l.jpg

A.2. Building blocks: Some Terms for describing Properties of Amino Acids

  • Hydrophobic amino acids are those with side-chains that do not like to reside in an aqueous (i.e. water) environment.

  • Polar amino acids are those with side-chains that prefer to reside in an aqueous (i.e. water) environment.

  • Strictly speaking, aliphatic implies that the protein side chain contains only carbon or hydrogen atoms.

  • A side chain is aromatic when it contains an aromatic ring system.

CS 6463: An overview of Molecular Biology


A 2 building blocks covalent and non covalent bonds l.jpg

A.2 Building Blocks: Covalent and Non-covalent Bonds

  • Covalent bonds: stronger. Nucleic acid and protein polymers are from by covalent binds connecting nucleotides and amino acids (respectively) to form a linear backbone

  • Non-covalent bonds: weaker and revisible. 4 types:

    • Hydrogen bonds: N – H –O [double-stranded DNA, protein folding, …etc

    • Ionic bonds: Ionic interaction between charged group, sat Na+ and Cl-

    • Van der Waals: Optimum attraction between two atoms.

    • Hydrophobic forces: Water is polar molecules,

CS 6463: An overview of Molecular Biology


A an overview of molecular biology24 l.jpg

A. An overview of molecular biology

A.1. Background

A.2. Building Blocks of Macromolecules

A.3. DNA structure

A.4. RNA transcription and Gene Expression

A.5. RNA processing

A.6. Translation, post-translation processing and protein structure

A.7. Project ideas

CS 6463: An overview of Molecular Biology


A 3 dna structure the phosphodiester bond l.jpg

A.3 DNA Structure: The Phosphodiester Bond

CS 6463: An overview of Molecular Biology


A 3 dna structure base pairing watson crick rule l.jpg

A.3 DNA Structure: base pairing (Watson-Crick Rule).

CS 6463: An overview of Molecular Biology


A 3 dna structure dna is a double stranded anti parallel helix l.jpg

A.3 DNA Structure: DNA is a double-stranded anti-parallel helix

  • %GC = 40%? How many % is G? C? A? T?

Complementary

DNA

(cDNA)

downstream

upstream

http://www.sumanasinc.com/webcontent/anisamples/molecularbiology/DNA_structure.html

CS 6463: An overview of Molecular Biology


A 3 dna structure dna is a double stranded anti parallel helix28 l.jpg

A.3 DNA Structure: DNA is a double-stranded anti-parallel helix

CS 6463: An overview of Molecular Biology


A 3 dna structure rna structure l.jpg

A.3 DNA Structure: RNA structure

palindrome

CS 6463: An overview of Molecular Biology


A 3 dna structure viral genomes l.jpg

A.3 DNA Structure: Viral Genomes

  • Highly Variable:

    • DNA or RNA

    • Single stranded or double stranded

    • Linear or Circular

    • Segmented and Multipartite

  • Virus normally replicate in the cytosol. Unusal Retrovirus duplicate itself in the nucleus (using reverse transcriptase)

CS 6463: An overview of Molecular Biology


A 4 dna structure the central dogma l.jpg

A.4 DNA Structure: The Central Dogma

Old 1-directional model

CS 6463: An overview of Molecular Biology


A an overview of molecular biology32 l.jpg

A. An overview of molecular biology

A.1. Background

A.2. Building Blocks of Macromolecules

A.3. DNA structure

A.4. RNA transcription and Gene Expression

A.5. RNA processing

A.6. Translation, post-translation processing and protein structure

A.7. Project ideas

CS 6463: An overview of Molecular Biology


A 4 transcription and gene expression transcription l.jpg

A.4 Transcription and Gene Expression:Transcription

intron

intron

exon

exon

exon

Pre-mRNA

5’ UTR

start

stop

3’ UTR

poly A

(complementary nucleotides)

(2nd key, May not be there)

(1st key)

intron

intron

exon

exon

exon

promoter

5’ UTR

start

stop

3’ UTR

TFBS

TFBS

5’

3’

(almost always there)

(mostly for non-housing gene)

cap

TFBS – Transcription factor binding site

pore

Nuclear membrane

CS 6463: An overview of Molecular Biology


A 4 transcription and gene expression gene regulation l.jpg

A.4 Transcription and Gene Expression:Gene Regulation

G

C

G

A G T C

U C A G

http://henge.bio.miami.edu/mallery/movies/transcription.mov

http://www-class.unl.edu/biochem/gp2/m_biology/animation/gene/gene_a2.html

CS 6463: An overview of Molecular Biology


A 4 transcription and gene expression rna polymerase l.jpg

A.4 Transcription and Gene Expression:RNA Polymerase

  • There are three classes of RNA Polymerases:

    • Polymerase I: Localized in the nucleolus. Transcribe rRNA (ribosome RNA) 28S, 18S 5.8S rRNA.

    • Polymerase II: All protein-coding genes most smRNAs. Unique in capping and polyadenylation.

    • Polymerase III: tRNA, other rRNAs, snRNAs. [The promoter can be downstream]

  • Pusedo-genes (gene fragments): Previously were genes

  • Only 2% of the human genome encode proteins.

CS 6463: An overview of Molecular Biology


A 4 transcription and gene expression trans and cis elements l.jpg

A.4 Transcription and Gene Expression: Trans- and cis-elements

Important: If pattern is there, does not necessary mean it is a cis-element.

CS 6463: An overview of Molecular Biology


A 4 transcription and gene expression promoters l.jpg

A.4 Transcription and Gene Expression: Promoters

Start from 1 not 0

CS 6463: An overview of Molecular Biology


A 4 transcription and gene expression enhancers and silencers transcription factors l.jpg

A.4 Transcription and Gene Expression: Enhancers and Silencers (Transcription Factors)

Many basepairs

away

CS 6463: An overview of Molecular Biology


A 4 transcription and gene expression tissue specific genes l.jpg

A.4 Transcription and Gene Expression: Tissue Specific Genes

  • House keeping genes: Genes encoding histone protein, ribosome protein. Always on.

  • Tissue or development-specific (non-housekeeping) genes:

    • Transcriptional inactive chromatin

    • Methylation of Cytosine, replacing a hydrogen (H) with methyl (CH3)

    • Transcription factors’ expression levels are low.

  • Microarrays measure the expression levels of genes

CS 6463: An overview of Molecular Biology


A an overview of molecular biology40 l.jpg

A. An overview of molecular biology

A.1. Background

A.2. Building Blocks of Macromolecules

A.3. DNA structure

A.4. RNA transcription and Gene Expression

A.5. RNA processing

A.6. Translation, post-translation processing and protein structure

A.7. Project ideas

CS 6463: An overview of Molecular Biology


A 4 transcription and gene expression transcription41 l.jpg

A.4 Transcription and Gene Expression:Transcription

intron

intron

exon

exon

exon

Pre-mRNA

5’ UTR

start

stop

3’ UTR

poly A

(complementary nucleotides)

(2nd key, May not be there)

(1st key)

intron

intron

exon

exon

exon

promoter

5’ UTR

start

stop

3’ UTR

TFBS

TFBS

5’

3’

(almost always there)

(mostly for non-housing gene)

cap

exon

exon

exon

5’ UTR

start

stop

3’ UTR

poly A

Massager RNA (mRNA)

pore

Nuclear membrane

Splicing the introns: http://www.sumanasinc.com/webcontent/anisamples/molecularbiology/mRNAsplicing.html

CS 6463: An overview of Molecular Biology


A 5 rna processing rna splicing l.jpg

A.5 RNA Processing: RNA Splicing

acceptor

donor

GT-AG spliceosome

AT-AC spliceosome (rare)

CS 6463: An overview of Molecular Biology


A 5 rna processing consensus sequences at splice donor acceptor and branch sites l.jpg

A.5 RNA Processing: Consensus Sequences at splice donor, acceptor and branch sites

CS 6463: An overview of Molecular Biology


A 5 rna processing mechanism of rna splicing gu ag introns l.jpg

A.5 RNA Processing: Mechanism of RNA Splicing (GU-AG introns)

Splicesome

(5 snRNA)

http://www.nature.com/nrn/journal/v2/n1/animation/nrn0101_043a_swf_MEDIA1.html

CS 6463: An overview of Molecular Biology


A 5 rna processing 5 end capping l.jpg

A.5 RNA Processing: 5’ End Capping

CS 6463: An overview of Molecular Biology


A 5 rna processing 3 end polyadenylated l.jpg

A.5 RNA Processing: 3’ end polyadenylated.

CS 6463: An overview of Molecular Biology


A 5 rna processing functions of 5 end cap and poly a tail l.jpg

A.5 RNA Processing: Functions of 5’ End Cap and Poly A tail

  • Functions of 5’ end cap

  • Prevent mRNA molecules degradation.

  • Facilitate transport to cytoplasm

  • RNA splicing

  • Facilitate translation

  • Function of 3’ end poly(A) tail

  • 1. Facilitate transport to cytoplasm

  • 2. Stabilize the mRNA in the cytoplasm

  • 3. Facilitate translation

CS 6463: An overview of Molecular Biology


A 5 rna processing example of the human b globin gene l.jpg

A.5 RNA Processing: Example of the human b-globin gene

CS 6463: An overview of Molecular Biology


A 4 rna processing export out of the nuclear l.jpg

A.4 RNA Processing: Export out of the nuclear

CS 6463: An overview of Molecular Biology


A an overview of molecular biology50 l.jpg

A. An overview of molecular biology

A.1. Background

A.2. Building Blocks of Macromolecules

A.3. DNA structure

A.4. RNA transcription and Gene Expression

A.5. RNA processing

A.6. Translation, post-translation processing and protein structure

A.7. Project ideas

CS 6463: An overview of Molecular Biology


A 5 rna processing the codon anticodon recognition l.jpg

A.5 RNA Processing: The Codon-anticodon Recognition

tRNA

(almost always)

http://henge.bio.miami.edu/mallery/movies/translation.mov

CS 6463: An overview of Molecular Biology


A 6 translation and post translational processing peptide bond formation l.jpg

A.6 Translation and Post-Translational Processing : Peptide Bond Formation

CS 6463: An overview of Molecular Biology


A 6 translation and post translational processing the genetic codes l.jpg

A.6 Translation and Post-Translational Processing: The Genetic Codes

C-terminal

N-terminal

OH

H

CS 6463: An overview of Molecular Biology


A 6 translation and post translational processing the genetic codes54 l.jpg

A.6 Translation and Post-Translational Processing: The Genetic Codes

- mitochondrial

wobble

64 possible codons: 1 Start codon AUG. 3 stop codons, 20 amino acids

Signal in mRNAs can lead to alternative interpretation of stop codons:

UGA  21st AA selencocysteine, UAG 22nd AA pyrrolysine.

CS 6463: An overview of Molecular Biology


Slide55 l.jpg

A.6 Translation and Post-Translational Processing: Multiple Post-Translational Cleavages of Polypeptide Precursors

CS 6463: An overview of Molecular Biology


A 6 translation and post translational processing protein secondary structure l.jpg

A.6 Translation and Post-Translational Processing: Protein Secondary Structure

CS 6463: An overview of Molecular Biology


A 6 translation and post translational processing quaternary l.jpg

A.6 Translation and Post-Translational Processing: Quaternary

Amino acid sequence  secondary structure  tertiary structure

Amino acid sequence

CS 6463: An overview of Molecular Biology


A 6 translation and post translational processing quaternary structure l.jpg

A.6 Translation and Post-Translational Processing: Quaternary Structure

Subunit – Come from different

polypeptide

Domains – section of a polypeptides

That have a specific functional structure

Hemoglobin – 4 subunits.

CS 6463: An overview of Molecular Biology


A 6 translation and post translational processing disulfide bridges l.jpg

A.6 Translation and Post-Translational Processing: Disulfide Bridges

CS 6463: An overview of Molecular Biology


A 6 translation and post translational processing post translational modification l.jpg

A.6 Translation and Post-Translational Processing: Post-translational Modification

  • http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hmg.table.103

CS 6463: An overview of Molecular Biology


A 6 translation and post translational processing protein sorting localization l.jpg

A.6 Translation and Post-Translational Processing: Protein Sorting (Localization)

1. Signal Peptide

2. Post-translational modification

CS 6463: An overview of Molecular Biology


A 6 translation and post translational processing cellular function of proteins l.jpg

A.6 Translation and Post-Translational Processing: Cellular Function of Proteins

  • Diverse cellular functions:

    • Enzymes – ‘cut things into pieces’

    • Receptors

    • Transport

    • Transcription factor

    • Signaling

    • Hormones

    • Strutural

    • .. etc

CS 6463: An overview of Molecular Biology


A an overview of molecular biology63 l.jpg

A. An overview of molecular biology

A.1. Background

A.2. Building Blocks of Macromolecules

A.3. DNA structure

A.4. RNA transcription and Gene Expression

A.5. RNA processing

A.6. Translation, post-translation processing and protein structure

A.7. Project ideas

CS 6463: An overview of Molecular Biology


A 7 summary central dogma simplify l.jpg

A.7 Summary: Central Dogma Simplify

Enzymes, Receptors,

... etc

CS 6463: An overview of Molecular Biology


A 7 summary don t forget about mitochondria l.jpg

A.7 Summary: Don’t forget about mitochondria!

CS 6463: An overview of Molecular Biology


A 7 summary life is more complex l.jpg

A.7 Summary: Life is more complex

CS 6463: An overview of Molecular Biology