Bi9 Lecture 8:
Principles of Signal Transduction 2
25 April 2013
In multicellular organism cells have to communicate to
control metabolism, growth, differentiation etc.
Single-cellular organisms communicate using
molecules called pheromones
Many of the slides from todays lecture came from David Baltimores lecture to the 2007 Bi1 class, which was based on a talk he gave in Physics in 2006.
What is a stem cell?
Has the capacity for selfrenewal. Can differentiate into two or more mature cell t
Is there any hope for an antibody-based therapeutic approach against HIV given that people dont normally make broadly neutralizing antibodies against HIV?
HIV rapidly mutates so that antibodies are no longer effective. HIV spike proteins are covered with
In thinking about vaccines, recall that there are two arms of the adaptive immune response
Cellular (Cytotoxic T Lymphocyte or CTL) response - works well for controlling (most) viral infections because viruses replicate intracellularly. Less adapted for
Putting biology to work for you:
In vitro (directed) evolution and other techniques
Make a combinatorial library of genes of interest Put genes into a vector so that each gene product is expressed on the surface of a bacteriophage
Antibodies against foreign MHC molecules can be isolated from the blood of transplantation patients and multiparous women (women who have had more than one baby). Which portion of the MHC molecule are the antibodies likely to recognize?
At what level is the polymorphism of MHC molecules a benefit? 1) An individual has a variety of MHC proteins to present various antigens. not wiped out by a single viral
2) A population infection. 3) Both.
Two types of T cells
Killer T cells. Also called cytotoxic T lymphocytes (CTLs)
Coreceptor: CD8 Recognize antigen bound by class I MHC molecules Can kill virally-infected cells
Helper T cells (TH cells)
Coreceptor: CD4 Recognize antigen bound by class
Caused by reactivation of Herpes Zoster Virus Infection of the nerve roots After recover from chicken pox, virus is dormant in nerve roots - usually dormant forever Virus can be reactivated by stress, aging, or a weakened immune system Reactiva
(What we and other vertebrates have in addition to an innate immune system)
Adaptive immune system
Makes specific immune response to a pathogen (1790s): Jenner showed that exposure to cowpox protected against infection by a related virus: smallpox Adapti
The Immune System
A complex system that is responsible for distinguishing us from everything foreign to us, and for protecting us against infections and foreign substances. The immune system works to seek and kill invaders. www.als.net/als101/glossary.asp
Swine flu is a dangerous form of influenza. Which of the following is true:
1) 2) 5) Swine flu is highly contagious amongst pigs, but does not infect humans. Swine flu is normally spread only amongst pigs, but can be caught by humans by e
Final steps in HIV assembly and budding from host cell
Figure 9-15 part 4 of 4
Note there are some inaccuracies in this figure (maturation to a bullet-shaped capsid occurs AFTER budding).
HIV needs to export unspliced, singly spliced, and multiply splic
CDC* definition of AIDS
A = Acquired = a virus received from someone else I = Immune = an individuals natural protection against disease-causing microorganisms D = Deficiency = a deterioration of the immune system S = Syndrome = a group of signs and sympt
Viruses are parasites
Viral genomes small - contain few genes compared with living cells
HIV genome has 9749 nucleotides - Human cells have ~3.2 x 109 base pairs (~30,000 genes)
Viruses must hijack host cells. They can only reproduce if they force the
Genomics & Genetic Engineering
DNA Interactive: http:/www.dnai.org/
Using recombinant DNA technology, we can: Sequence all the genes in an organism. Amplify genes (e.g., for forensics or to find viruses). Express rare proteins or construct new proteins by
DNA Interactive: http:/www.dnai.org/
Using recombinant DNA technology, we can: Sequence all the genes in an organism. Amplify genes (e.g., for forensics or to find viruses). Express rare proteins or construct new proteins by splicing t
The 2006 Nobel Prize in Medicine was given to Andrew Fire and Craig Mello for their work showing that _ can regulate the expression of genes. 1) 2) 3) 4) 5) 6) DNA RNA Protein Carbohydrates Lipids All of the above
What is the same in all* somatic cells of your body?
1) 2) 3) 4) 5) 6) DNA RNA Proteins Lipids Carbohydrates Lysosomes
* Some immune cells are interesting exceptions.
The DNA in differentiated cells contains all the instructions to make a new organism
Propose a mechanism by which the highlighted areas could cause transcription to stop.
The first two sequences are inverted repeats of each other, thus a hairpin, which is a signal for termination.
How can tRNAs and other hairpincontain
Macromolecular structures Nucleic acids
Carbohydrates Lipids Proteins
Proteins: Sequence -> Structure -> Function
Anfinsen Experiment: Denature ribonuclease (RNase) Remove denaturant Assay for RNase activity - does the protein regain its 3-D stru
Tertiary Structure: An Example of an All-Alpha Protein, Hemoglobin Subunit
Rotated 90 Degrees
Tertiary Structure: An Example of an All-Beta Protein, Flu Virus Neuraminidase
1) Rotate 90 Degrees
Tertiary Structure: An Example of an Alpha/ Beta Protein, Tri
You can use the electron density equation to calculate an electron density map once you have amplitudes and phases for every hkl
(h,k,l are indices for diffraction maxima in reciprocal space)
Coordinates are deposited in the Protein Data Base (PDB)