Bi 1 Syllabus

Spring 2009

 

Course Description

Professor: Pamela J. Bjorkman

This course introduces non-biologists to recent advances in our understanding of how HIV and other viruses infect and cause damage to their hosts. Because understanding and treating HIV infection involves a basic knowledge of cell and molecular biology, virology, and immunology, the course will cover fundamental concepts in these areas from a quantitative, molecular, chemical and biophysical perspective.

Textbook

The required textbook is Biological Science, 3/E, by Scott Freeman (ISBN-10: 0321543270). Click to search for the lowest prices on booksprice.com.
You may also use the second edition of the textbook if you would like (it is probably easier to find a used copy of this version); it is not necessary to purchase the MasteringBiology™ online access package. Reading for both the second and third editions is listed below.

Bi1 docsNtalks group
http://www.docsntalks.com/group/bi1-2009

docsNtalks is an online tool for storing and viewing documents, with an emphasis on facilitating discussion and collaboration for conferences, workshops and work-groups. Bi1 lectures will be available on docsNtalks (in addition to this website) where you can view them in your browser and discuss them (after registration).

Schedule

Unless otherwise noted, Bi1 homeworks are due on Tuesdays at 4:00 PM. They will generally be returned to students in section the following week.

#	Lecture Topic	Lecturer	Reading 3/E	Reading 2/E	Homework & Exams	Date
1	Introduction to Bi 1	PJB	Ch. 1	Ch. 1	PS 1 posted	Mon, 3/30
2	Eukaryotic cells and organelles	PJB	Ch. 7	Ch. 7		Wed, 4/01
3	Biological imaging	PJB	B14-B16	--		Fri, 4/03
4	Macromolecular Structure I:	PJB	Ch. 3-6	Ch. 3-6		Mon, 4/06
					PS 1 due PS 2 posted	Tue, 4/07
5	Macromolecular Structure II:	PJB	Ch. 3-6	Ch. 3-6		Wed, 4/08
6	Central Dogma I: Replication	RO	Ch. 14	Ch. 14		Fri, 4/10
7	Central Dogma II: Transcription	PJB	Ch. 16	Ch. 16		Mon, 4/13
					PS 2 due PS 3 posted	Tue, 4/14
8	Central Dogma III: Translation	PJB	Ch. 16	Ch. 16		Wed, 4/15
9	Gene regulation: transcriptional regulation	PJB	Ch. 17-18	Ch. 17-18		Fri, 4/17
10	Gene regulation: RNAi	PJB	p. 381-2	--		Mon, 4/20
					PS 3 due PS 4 posted	Tue, 4/21
11	Molecular biology I: (basic cloning)	PJB	Ch. 19	Ch. 19		Wed, 4/22
12	Molecular biology II (genomics)	PJB	Ch. 20	Ch. 20		Fri, 4/24
13	Icosahedral viruses	PJB	Ch. 35	Ch. 34		Mon, 4/27
					PS 4 due	Tue, 4/28
14	HIV lifecycle I	PJB	Ch. 35	Ch. 34	Midterm posted	Wed, 4/29
	Midterm review, Wed 4/29, 4-6pm, 119 Kerckhoff	TAs
15	HIV lifecycle II	PJB	Ch. 35	Ch. 34		Fri, 5/01
16	Swine flu	PJB	Ch. 35	Ch. 34	Midterm due	Mon, 5/04
					PS 5 posted	Tue, 5/05
17	Innate Immunity	PJB	Ch. 49	Ch. 49		Wed, 5/06
18	Antibodies	PJB	Ch. 49	Ch. 49		Fri, 5/08
19	Antibodies, Binding Data, Flow cytometry	PJB	Ch. 49	Ch. 49		Mon, 5/11
					PS 5 due PS 6 posted	Tue, 5/12
20	MHC, T-cells I	PJB	Ch. 49, 20, 35	Ch. 49, 20, 34		Wed, 5/13
21	MHC, T-cells II	PJB	Ch. 49, 20, 35	Ch. 49, 20, 34		Fri, 5/15
22	Neutralizing Antibodies against HIV	PJB	Ch. 35, 49	Ch. 34, 49		Mon, 5/18
					PS 6 due PS 7 posted	Tue, 5/19
23	In vitro evolution	PJB	--	--		Wed, 5/20
24	Vaccines I	PJB	Ch. 49	Ch. 49		Fri, 5/22
	Memorial Day					Mon, 5/25
					PS 7 due PS 8 posted	Tue, 5/26
	Ditch Day	PJB	Ch. 49	Ch. 49		Wed, 5/27
25	Vaccines II	PJB	Ch. 49	Ch. 49		Fri, 5/29
26	Stem Cells	PJB	Ch. 19, 22	Ch. 19, 22		Mon, 6/01
					PS 8 due	Tue, 6/02
27	Paul Rothemund Lecture	PR				Wed, 6/03
	Final review, Wed 6/03, 4-6 pm, 119 Kerckhoff	TAs
28	Niles Pierce lecture	NP			Final posted	Fri, 6/05
					Final due	Thurs, 6/11

Lecture 1: Introduction to Bi 1

Download: PDF - handout (4.7 MB) | PDF - full (5.0 MB) | PPT (5.0 MB)

Links:

• http://www.apla.org/facts/HIV_statistics_current.pdf
  Current statistics for HIV infection and AIDS in Los Angeles County
• http://en.wikipedia.org/wiki/Image:HIV_Epidem.png
  Figure showing worldwide HIV prevalence
• http://www.kff.org/hivaids
  Fact Sheet: The Global HIV/AIDS epidemic (May 2006) from the Kaiser Family Foundation
• http://www.ted.com/index.php/talks/nathan_wolfe_hunts_for_the_next_aids.html
  Nathan Wolfe, an epidemiologist and visiting professor at Stanford, discusses his research hunting for deadly viruses before they become pandemics.
  

 

Lecture 2: Eukaryotic cells and organelles

Download: PDF - handout (1 MB) | PDF - full (5.5 MB) | PPT (zip file, with movies - 93 MB)

Links:

• The Inner Life of the Cell
  Short segments of this movie were included in today's lecture. You can watch the whole movie here. It focuses upon leukocyte migration through blood vessel walls into inflamed tissues, which we will discuss in Lecture 16. It is highly recommended that you watch the movie in its entirety (~7 minutes), because it covers many of the processes we will discuss in class.
• What's the Difference Between LDL and HDL Cholesterol?
  Discusses the difference between HDL (good cholesterol) and LDL (bad cholesterol).

 

Lecture 3: Biological imaging

Download: PDF - handout (1.5 MB) | PDF - full (8 MB) | PPT (zip file, with movies - 42.3 MB)* | Webcast (.mov - 35.4 MB, Caltech only)**
* Some movies have been omitted from the posted version to reduce space. These are available by emailing Damien.
** Movie playback is not supported within webcasts; please watch the video files in the PPT zip file. The webcast is in QuickTime (.mov) format and requires the free Quicktime player to view (available at www.apple.com/quicktime)

Links:

• The Jensen Laboratory for Cryo-Electron Microscopy
  Cryo-EM tomography at Caltech—click on Cool Movies.
• The Boulder Laboratory for 3D Electron Microscopy of Cells
  Click on Movies and Data sets.
• Marsh et al. 98:2399 Data Supplement
  Movies of 3D reconstruction of pancreatic cells derived by electron tomography.
• MicroscopyU
  Lots of great microscopy intros and tutorials -- run by Nikon.

Lecture 4: Macromolecular structure I

Download: PDF - handout (1.2 MB) | PDF - full (5.6 MB) | PPT (zip file, with movies - 55.3 MB) | Webcast (.mov - 28.2 MB, Caltech only)**
** Movie playback is not supported within webcasts; please watch the video files in the PPT zip file. The webcast is in QuickTime (.mov) format and requires the free Quicktime player to view (available at www.apple.com/quicktime)

Suggested reading:

• Rosalind Franklin: The Dark Lady of DNA by Brenda Maddox
  Biography of the crystallographer who obtained the diffraction image of B form DNA that led to the solution of DNA's structure.
• Crick: The genetic code is read three bases at a time -- Excerpt from "How Scientists Think" (PDF, Caltech only)
  In 1961, Francis Crick and coworkers, in one of the best experiments anyone has ever done, demonstrated that the actual instructions for a protein exist as a series of nonoverlapping, three-base code words, each "triplet" specifying one of the 20 amino acids.

Links:

• DNA Interactive
  Many of the movies shown in class come from this site. It also includes interviews with scientists who made critical discoveries in molecular biology, biotechnology, and/or recombinant DNA research.
• NOVA | Secret of Photo 51 | PBS
  Discusses the contributions of Rosalind Franklin to the discovery of the structure of DNA. Includes an explanation of Franklin's famous "X"-shaped diffraction pattern of DNA, which demonstrates that DNA is helical.
• Rosalind Franklin and the Double Helix, by Lynne Osman Elkin, Physics Today, March 2003
  The history of the discovery of the structure of DNA. Corrects some of the distortions about Franklin that appear in James Watson's book "The Double Helix".
• Caltech Archives Oral Histories Online - Interview with Linus Pauling
  Interview in 1984 with Linus Pauling, Caltech Professor of Chemistry, recipient of the Nobel Prize in Chemistry (1954; for "his research on the nature of the chemical bond") and the Nobel Peace Prize (1962). Pauling discusses the Biology Division at Caltech, Thomas Hunt Morgan, his work on hemoglobin in the 1930s, immunology, and his discovery of the alpha-helix.
• JenaLib: The Amino Acid Repository
  Structures and properties of the 20 amino acids in proteins
• Tangible Interfaces for Molecular Biology
  Hands-on models of proteins
• Kevin Cowtan's Picture Book of Fourier Transforms
  Nice tutorial on the use of Fourier transforms in X-ray crystallography
• The RCSB Protein Data Bank
  An archive of the coordinates of the structures of macromolecules determined by X-ray crystallography, NMR, and electron microscopy.
• The Molecular Observatory
  The Molecular Observatory provides the Caltech community with exceptional capabilities in macromolecular crystallography, including a synchrotron radiation beam line at SSRL and an on-campus crystallization laboratory providing state-of-the-art robotics for crystallization.

Lecture 5: Macromolecular structure II

Download: PDF - handout (0.5 MB) | PDF - full (4.7 MB) | PPT (zip file, with movies - 22.4 MB)

For reading, see lecture 4.

 

Lecture 6: Central Dogma I: Replication

Download: PDF - handout (1 MB) | PDF - full (2.5 MB) | PPT (zip file, with movies - 18.4 MB)

Suggested Reading:

• The DNA replication problem, 1953–1958, Frederic L. Holmes, Trends in Biochemical Sciences, Volume 23, Issue 3, 1 March 1998, Pages 117-120
  This article describes some of the intellectual challenges faced in thinking about DNA replication.

Lecture 7: Central Dogma II: Transcription

Download: PDF - handout (0.9 MB) | PDF - full (4.6 MB) | PPT (zip file, with movies - 39.3 MB) | Webcast (.mov - 27.1 MB, Caltech only)**
** Movie playback is not supported within webcasts; please watch the video files in the PPT zip file. The webcast is in QuickTime (.mov) format and requires the free Quicktime player to view (available at www.apple.com/quicktime)

Links:

• What the heck is a gene?
  
• The DNA and Natural Algorithms Group: Publications
  Erik Winfree's lab at Caltech is using DNA to make digital logic circuits. They are able to demonstrate AND, OR, and NOT gates, signal restoration, amplification, feedback and cascading. See Seelig et al., 2006, Science 314: 1585-1588
• RNA Structure and Prediction
  Prediction of RNA structure
• Paul W.K. Rothemund home page
  Design of DNA origami
• DNA supercoil from Wikipedia
  Introduction to DNA supercoiling including mathematical modeling
• Chemistry 2006
  The Nobel Prize in Chemistry 2006 given to Roger Kornberg for his studies of the molecular basis of eukaryotic transcription —largely awarded for his structural studies of RNA polymerase.
• The Molecular Programming Project
  Caltech's Molecular Programming Project is developing new computer science principles using DNA and RNA for computation
  

Lecture 8: Central Dogma III: Translation

Download: PDF - handout (1.3 MB) | PDF - full (3.7 MB) | PPT (zip file, with movies - 30.8 MB) | Webcast (.mov - 27.2 MB)

Links:

• The Genetic Code
  Brief description of the history of solving the genetic code.
• The RNA world: History of an idea, an idea of history
  Discusses idea that RNA was the first life-form on earth. The hypothesis is support by the facts that RNA can store, transmit and duplicate genetic information as well as function as an enzyme to catalyze reactions. See also The RNA World (nobelprize.org).
• Protein synthesis: an epic on the cellular level (YouTube) - A 1970s take on protein synthesis.
  

Lecture 9: Gene regulation (transcriptional regulation)

Download: PDF - handout (1 MB) | PDF - full (5 MB) | PPT (zip file, with movies - 34.1 MB) | Webcast (.mov - 27 MB)

Lecture 10: RNAi

Download: PDF - handout (1 MB) | PDF - full (3 MB) | PPT (zip file, with movies - 12.1 MB) | Webcast (.mov - 24.3 MB)

Reading:

• Derek M. Dykxhoorn and Judy Lieberman "The Silent Revolution: RNA Interference as Basic Biology, Research Tool, and Therapeutic" Annual Reviews of Medicine 2005 (56): p. 401-23 (PDF, Caltech only)
• Carol A. Sledz and Bryan R. G. Williams " RNA interference in biology and disease" Blood. 2005 (106): p. 787-94 (PDF, Caltech only)

Links:

• RNAi resource at Ambion
  This company sponsored website provides a wealth of basic information about RNAi principles, tools and techniques.
• Mello's Nobel lecture
  Mello and Fire won the 2006 Nobel prize for their discovery of RNAi
• RNAi animation from Nature.com
  This video provides an animated tour of the RNAi process.
  

Lecture 11: Molecular biology I: basic cloning

Download: PDF - handout (643 KB) | PDF - full (2.5 MB) | PPT (zip file, with movies - 29 MB) | Webcast (.mov - 26.5 MB)

Links:

• Plasmid cloning (YouTube) - A brief overview of DNA subcloning.
• Restriction enzymes (YouTube) - A video description of restriction enzymes.
• The test-tube synthesis of a chemical called poliovirus. Wimmer, E. EMBO Reports 7: S3-S9 (2006).
  The simple synthesis of a virus has far-reaching societal implications.
• DNA Interactive
  Many of the movies shown in class come from this site. It also includes interviews with scientists who made critical discoveries in molecular biology, biotechnology, and/or recombinant DNA research.
• Gene Expression in Cultured Cells
  This website has lots of interesting discussion of strategies for putting foreign DNA into different types of cells.
• Roche Applied Science: Cutting-Edge Transfection Reagents
  This site gives a discussion of different products that are used to transfect cells. (If you go to this URL, you may be asked to select your country. Just select "United States" and hit Go.)
• 1993 Nobel Prize in Chemistry
  Kary Mullis (PCR) and Michael Smith (site directed mutagenesis)
  

Lecture 12: Molecular biology II: genome science, sequencing

Download: PDF - handout (1.1 MB) | PDF - full (5.2 MB) | PPT (zip file, with movies - 59 MB) | Webcast (.mov - 27 MB)

Links and Reading:

• genome.gov | 2003 Release: International Consortium Completes HGP
  The press release announcing the completion of the public human genome project.
• Human Genome Projects Information
  All about the Human Genome Project.
• Centre for Integrated Genomics
  "Development and application of genome science to the diagnosis and treatment of cancer"
• Commonality with other organisms
  A page exploring similarity of genomes among different species.
• Steven Pinker - "My genome, my self"
  An article published in the New York Times magazine by scientist Steven Pinker describing personal genomics (and the mapping/analysis of his own genome).

Lecture 13: Icosahedral viruses

Download: PDF - handout (796 KB) | PDF - full (5.6 MB) | PPT (zip file, with movies - 61.2 MB) | Webcast (.mov - 27 MB)

Reading:

• Adding the third dimension to virus life cycles: three-dimensional reconstruction of icosahedral viruses from cryo-electron micrographs, Baker et al., Microbiol Mol Biol Rev Dec 63:862 (1999)
  This gorgeous paper gives a variety of structural insights into the construction of viruses. It is also a nice review of the techniques for 3-D reconstruction of icosahedral viruses by electron microscopy.
• Geometry of Phage Head Construction, Moody, J. Mol. Biol. 293:401 (1999)
  This is a wonderful review paper discussing the architecture of phage capsids from a geometrical and physical perspective. Nanotechnology at its finest.
• Structural Biology of HIV, Turner and Summers, J. Mol. Biol. 285:1 (1999)
  This article describes both the life cycle and parts list of HIV.

Links:

• Virus Ultrastructure
  An introduction to virology, by an electron microscopist. Contains EM images of many different viruses.
• Principles of Virus Architecture
  From the Virus Ultrastructure site above, a page on the geometrical principles of virus capsid construction.
• All the Virology on the WWW
  A very large and comprehensive site with information on all aspects of virology, as well as links to course notes, tutorials, graduate programs, and more.
• The Big Picture Book of Viruses
  A massive catalog of virus pictures on the internet. Part of All the Virology on the WWW.
• Geodesic Domes
  A page on Buckminster Fuller's triangulated domes, mathematically similar to viral capsids and carbon fullerenes.
• Virus Structure
  A brief overview of virus structure, discussing HIV (incorrectly) as well as examples of helical and icosahedral viruses.
• Virus particle explorer
  Database and website for icosahedral virus structures and their analysis.

Lecture 14: HIV life cycle I

Download: PDF - handout (776 KB) | PDF - full (5.2 MB) | PPT - 6 MB | Webcast (.mov - 25.4 MB)

Suggested Reading:

• Molecules of HIV
  This website will help you understand the parts list of HIV.
• Interactive Multimedia Textbook of HIV/AIDS
  Links to many articles about scientific and clinical aspects of HIV/AIDS.
• HIVinfosource
  Animations of various steps in the HIV lifecycle.
• HIV Lifecycle
  Allows you to step through an animation of the steps in the HIV lifecycle, with an explanation for each. Also information on mode of action of fusion inhibitors, reverse transcriptase inhibitors and protease inhibitors.

Further reading:

• Visualization of the intracellular behavior of HIV in living cells, McDonald et al., J Cell Biol 159:441 (2002)
  Live cell imaging of HIV accomplished by observing GFP-tagged viruses in infected cells.
• Unchain my heart, baby let me go—the entry and intracellular transport of HIV, Sodeik, J Cell Biol 159:393 (2002)
  Commentary on above paper.

Links:

• Structure-based drug design: From the computer to the clinic.
  Focuses on design of anti-HIV drugs and includes an overview of the HIV lifecycle.
• Attacking AIDS with a 'Cocktail' Therapy
  FDA Consumer magazine article on HAART (highly active anti-retroviral therapy)
• FDA-approved Anti-HIV Drugs
  FDA-approved anti-HIV drugs, including HIV protease inhibitors

Midterm Review

Download: PDF (handout) - 2.4 MB | PDF (full) - 12.3 MB

Lecture 15: HIV life cycle II

Download: PDF (handout) - 886 KB | PDF (full) - 2.5 MB | PPT (zip file, with movies - 112.4 MB) | Webcast (.mov - 25.4 MB)

See links for lecture 14.

Lecture 16: Swine flu

Download: PDF (handout) - 1.2 MB | PDF (full) - 3.5 MB | PPT - 6.4 MB | Webcast (.mov - 27.3 MB)

Links:

• Focus on the Flu Research: Flu Primer NIAID
  This site provides a basic overview of flu virus.
• Swine flu mini science primer
  Swine flu and its sensitivity to anti-viral drugs.
• CDC Swine flu resources
  CDC statistics about swine flu.
• Pandemicflu.gov
  One-stop access to US Government swine, avian, and pandemic flu information
• Virus Entry into Cells
  This primer provides an introduction to viral entry.
• Explore the Science and History of Influenza" (a discussion with Alice Huang)
  An interview about Alice Huang about avian flu and the influenza virus (also applicable to swine flu).
• NCBI Influenza Viruses Resource - Information, Search and Analysis
  This National Institutes of Health contains NIAID flu genome sequences and other flu information
  

Lecture 17: Innate immunity

Download: PDF (handout) - 343 KB | PDF (full) - 3.9 MB | PPT (zip file, with movies - 22.6 MB) | Webcast (.mov - 22.6 MB)

Suggested Reading:

• Understanding the Immune System: How It Works
  A primer on immunology that introduces the cells and molecules of the immune system.
• The Health Library — Immune System
  Web resources about the immune system.
• How the Immune System Works by Lauren M. Sompayrac
  

Links:

• The Inner Life of the Cell
  This movie focuses upon leukocyte migration through blood vessel walls into inflamed tissues, which is discussed in the extra slides at the end of this lecture. It is highly recommended that you watch the movie in its entirety (~7 minutes), because it covers many of the processes we will discuss in class.
• Leukocyte Extravasation
  An interactive animation on leukocyte migration through blood vessel walls into inflamed tissues, as discussed in the extra slides for today's lecture.
• immunoanimations
  Animations from the Immunobiology textbook (Janeway et al.)
• Neutrophil Hunting
  A neutrophil hunting for a pathogen to eat.

Lecture 18: Antibodies

Download: PDF (handout) - 1 MB | PDF (full) - 4.9 MB | PPT (zip file, with movies - 16.3 MB) | Webcast (.mov - 24.8 MB)

Links:

• What the heck is an antibody?
  
• Mike's Immunoglobulin Structure/Function Home Page
  Pictures of antibody molecules
• The Antibody Resource Page
  Links to commercial antibody products.
• Ask Lenore ~ Breastfeeding: How Breast Milk Protects Newborns
  How breast feeding protects newborns (antibodies and other useful molecules)
• immunoanimations
  Animations from the Immunobiology textbook (Janeway et al.) Click on the orange textbook once you get to this site, then choose which animation you want to watch.
• Immunotherapy for Cancer - Monoclonal Antibodies
  Monoclonal antibodies used to treat cancer
• Medicine 1984
  The 1984 Nobel Prize in Physiology or Medicine was given to Niels Jerne, Georges Kšhler, and Cˇsar Milstein "for theories concerning the specificity in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies".
• Medicine 1987
  The 1987 Nobel Prize in Physiology or Medicine was given to Susumu Tonegawa "for his discovery of the genetic principle for generation of antibody diversity" (i.e., for discovery that antibodies are made by combining different gene segments in B cells)

Lecture 19: Antibodies/binding data/flow cytometry

Download: PDF (handout) - 1.1 MB | PDF (full) - 6.2 MB | PPT - 8.5 MB | Webcast (.mov - 25.8 MB)

See links for lecture 18.

Lecture 20: MHC/T cells I

Download: PDF (handout) - 424 KB | PDF (full) - 1.4 MB | PPT (zip file, with movies - 18 MB) | Webcast (.mov - 26.1 MB)

Links:

• What the heck is an MHC molecule?
  
• Medicine 1996
  The 1996 Nobel Prize in Physiology or Medicine was given to Peter Doherty and Rolf Zinkernagel "for their discoveries concerning the specificity of the cell mediated immune defense" (i.e., for the discovery of MHC-restricted recognition of antigen by T cells)
• Anthony Nolan Research Institute - HLA Informatics Group
  HLA informatics web page
• MHCPEP
  Database of peptides that bind to different MHC alleles
• immunoanimations
  Animations from the Immunobiology textbook (Janeway et al.)
• Pop quiz: What is the rate of mistaken paternity?
  A web page discussing the evidence on the rates of mistaken paternity (probably not as high as 10%).

Lecture 21: MHC/T cells II

Download: PDF (handout) - 915 KB | PDF (full) - 3.2 MB | PPT (zip file, with movie - 11.7 MB) | Webcast (.mov - 25.2 MB)

Reading:

• see lecture 20 for list
  

Links:

• IMGT Databases at the EBI
  T cell receptor and antibody sequences
• immunoanimations
  Animations from the Immunobiology textbook (Janeway et al.) Click on the orange textbook once you get to this site, then choose which animation you want to watch.
• Body odour preferences in men and women: do they aim for specific MHC combinations or simply heterozygosity?
  Wedekind & FŸri, 1997, Proc. R. Soc. Lond. B. 264:1471-9. The T-shirt paper suggesting that MHC or linked genes influence human mate choice.
• Forget Mistletoe, What about DNA? (PDF, Caltech only)
  An article that describes the story behind scientificmatch.com, a dating website that matches people based on MHC polymorphism.

Lecture 22: NAbs against HIV

Download: PDF (handout) - 1.4 MB | PDF (full) - 8.6 MB | PPT (zip file, with movie - 9.2 MB) | Webcast (.mov - 27.6 MB)

Reading:

• An AIDS vaccine: no time to give up. Burton et al., Lancet 364:1938 (2004). [PDF, Caltech only]
  A one-page letter to the editor in the British medical journal Lancet, arguing for optimism in AIDS vaccine development.
• Antibody vs. HIV in a clash of evolutionary titans. Burton et al., PNAS 102:14943 (2005). [PDF, Caltech only]
  A nice review on neutralizing antibodies against HIV. Beautifully illustrated.
• Correlates of immune protection in HIV-1 infection: what we know, what we don't know, what we should know. Pantaleo and Koup. (2004) Nat Med 10:806. [PDF, Caltech only]
  A review on mechanisms of HIV vaccines.

Links:

• Center for HIV-AIDS Vaccine Immunology
  A description of on-going vaccine trials.

Lecture 23: In vitro evolution

Download: PDF (handout) - 751 KB | PDF (full) - 2.3 MB | PPT - 6.6 MB | Webcast (.mov - 27.4 MB)

Links:

• Dyax: Phage display discovery tool
  Includes an animation of phage display.
• The Ellington Lab Aptamer Database
  A comprehensive, annotated repository for information about aptamers and in vitro selection.
• Directed Evolution course at MIT
  This class (MIT 7.344) teaches the fundamentals of directed evolution with an emphasis on enzymes that are used in the synthesis of drugs and in biotechnological applications.
• Frances Arnold Lab at Caltech
  Research in the Arnold group focuses on evolutionary design methods applied to biological systems and use of the results of laboratory evolution experiments to elucidate principles of biological design.
• Steve Mayo Lab at Caltech
  The Mayo lab focuses on developing quantitative methods for protein design.
  
  

Lecture 24: Vaccines I

Download: PDF (handout) -305 KB | PDF (full) - 715 KB | PPT - 1.9 MB | Webcast (.mov - 22.2 MB)

Reading:

• Whole-Killed Vaccines, NIAID Division of AIDS, HIV Vaccine Site
  Attempts to make an HIV vaccine using a traditional approach (whole-killed viruses)
• Live-Attenuated Viruses, NIAID Division of HIV Vaccine Site
  Considerations for the use of live-attenuated viruses as vaccines against HIV
• Live attenuated HIV vaccines: pitfalls and prospects. Whitney and Ruprecht. (2004) Curr Opin Infect Dis. 17:17.
  
• Correlates of immune protection in HIV-1 infection: what we know, what we don't know, what we should know. Pantaleo and Koup. (2004) Nat Med 10:806.
  A review on mechanisms of HIV vaccines.
• Gene therapy
  The Wikipedia entry for gene therapy.
• 'Miracle' gene therapy trial halted
  Gene therapy trials to treat SCID halted because of induced cancers directly related to the treatment.
• Targeting lentiviral vectors to specific cell types in vivo. Yang et al. (2006) PNAS 103:11479
  Research done in the laboratory of David Baltimore (former Caltech President) as part of the Engineering Immunity project.
• Information on the Merck HIV vaccine trial:
  • HIV vaccine may have made people more vulnerable to infection
  • CROI: AIDS vaccine: additional infection risk restricted to uncircumcised men

Links:

• FAQs: Avian Flu
  Frequently asked questions about bird flu.
• The 1918 Spanish Flu Pandemic, and the Emerging Bird Flu Pandemic
  
• What the heck is a DNA vaccine?
  
• Center for HIV-AIDS Vaccine Immunology
  A description of on-going vaccine trials.

Please also see links from lecture 22.

Lecture 25: Vaccines II

Download: PDF (handout) - 1.4 MB | PDF (full) - 6.5 MB | PPT - 16.4 MB | Webcast (.mov - 25 MB)

See links for lecture 24.

Lecture 26: Stem Cells

Download: PDF (handout) - 819 KB | PDF (full) - 4.5 MB | PPT (zip file, with movie) - 5.9 MB | Webcast (.mov) - 25.8 MB

Reading:

• 5 things to know before jumping on the iPS bandwagon. David Cyranoski, Nature 452, 406-408 (2008) [PDF, Caltech only]
  A discussion of induced pluripotent stem cells
• Benefits of the stem cell ban. John D. Loike and Ruth L. Fischbach, The Scientist, 8th June 2009 (Caltech only)
  Federal aversion to embryonic stem cell research had a silver lining: it galvanized the development of new biotechnologies in stem cell science, two bioethicists argue

Links:

• NIH website on stem cells
  http://stemcells.nih.gov/index.asp
• NIH glossary of stem cell terms:
  http://stemcells.nih.gov/info/glossary.asp
• Information about California's Proposition 71
  http://igs.berkeley.edu/library/htProp71StemCell.html
• California Institute for Regenerative Medicine
  http://www.cirm.ca.gov/
• Cloning fact sheet -- defines and discusses molecular cloning, reproductive cloning, therapeutic cloning
  http://www.ornl.gov/sci/techresources/Human_Genome/elsi/cloning.shtml
• President Obama's stem cell executive order
  http://www.whitehouse.gov/the_press_office/Removing-Barriers-to-Responsible-Scientific-Research-Involving-Human-Stem-cells/
• Signing of Stem Cell Executive Order and Scientific Integrity Presidential Memorandum
  http://www.whitehouse.gov/the_press_office/Remarks-of-the-President-As-Prepared-for-Delivery-Signing-of-Stem-Cell-Executive-Order-and-Scientific-Integrity-Presidential-Memorandum/
  

Lecture 27: Paul Rothemund Guest Lecture

This lecture will not be posted for download.

Links:

• Paul Rothemund's homepage
  http://www.dna.caltech.edu/~pwkr/

Final Review

Download: PDF (handout) - 1.4 MB | PDF (full) - 9.9 MB | PPT (zip file, with movie) - 17.2 MB

Lecture 28: Niles Pierce Guest Lecture

This lecture will not be posted for download.

Links:

• Niles Pierce Lab at Caltech
  http://piercelab.caltech.edu/