July 5 connection between viruses and cancer

Review:

Known oncogenes (turned OFF or ON to cause cancerous behavior)

•  Loss of tumor suppressor genes
• Normally on- inhibit mitosis in abnormal cells
• Loss of apoptosis 
• Normally on - cause abnormal cells to commit suicide
• Example p53 tumor suppressor.... picture..of development of figure and toes that use apoptosis to divide them, example of child who have two fused fingers instead of seperating
•  Angiogenesis
• Normally off - growth of new blood vessels into mass of new cells
• What is Tumor Angiogenesis? picture: small localized tumor.... angiogenesis causes tumor that can grow and reproduce becuse new blood vessels to bring nutrients
•  Metastasis
• normally off- separation and spread of cells 

Has to have at least TWO of these genes turned on.

can test for breast cancer genes....

colon cancer diagrams...
* APC gene on chromosome 5 mutated... RAS mutation on chromosome 12... lost tumor suppressor gene chromosome 18... P53 on chromosome 17

**** group activity:

*human papilloma virus infections may lead to cervical cancer. Answer the following:

1. since it's naked, what ligand does it use for attachment? capsomeres
2. which of the two viral life cycles must it use? lysogenic cycle
3. If the virus does not have reverse transcriptase what genome must it have? dsDNA
4. name one enzyme that it MUST have. integrase
5. what general type of human gene must it insert near? proto-oncogene
6. what do you call the viral genome when it is inserted into the host genome? Provirus 

*** if cancerous then it must be lysogenic ****

Prion Diseases

* prion are even smaller then viruses because they are just individual proteins

• *proteinaceous infectious agents
• "mad cow disease" - bovine spongiform encephalopathy
• diagnosis: appearance of brain at autopsy: 
• Plaques or fibrous masses of proteins block normal nerve cell movement
• brain becomes spongy (spaces or gaps where no tissue connect to each other)
• fig 13.22 (altimezers cause plaques in the brain as well)

a)CJD (human version of mad cow disease, genetic)

b)vCJD (human version of mad cow disease, from tainted meat)

c)Kuru (human)

d)BSE (mad cow disease)

Molecular Nature of disease:

Fig 13.21

* normally occuring proteins (PrPP) 

  - alpha helix (flexible)  

*converted to deformed version of same proteins (PrPsc)

 - Beta sheet (flat, stiff) 

coils are not stable... how prions may work: prion converts normal protein into new prion

 * Scrape is prion disease in sheep and goats = (sc)

* CJO: motor, logic reasoning
*FRI thalomus (inability to sleep 1 1/2 years later = coma and die) 
*GSS and Kuru (motor skills?)

*Scrapie: disease of sheep 

- scrape their bodies raw by rubbing against fences, posts, etc. (founder animal: illegal to sell for human food, sometimes used for animal feed) 
- gradual loss of strength, inability to stand, erratic behavior (afraid water, biting one another, walk into wall instead of door)

Kuru

- 1st human prion disease studied
- Stanley Pruisner - Nobel prize for medicine
- Fore tribe in New Guinea 
- Trembling disease: gradual loss of motor control and death
- transmitted by cannibalism (elders brain eaten by young or women) (men eat muscle and meat of enemies)
         - ritual eating of relatives' remains
         - brains eaten by women and children (most infectious part) highest rate of disease
         - skin and muscle eaten by men
*no longer evident because tribe no longer cannibalistic 

Creutzfeldt- Jakob Disease

*typical disease: hereditary disease in 50-75 year old individuals.
         -slow onset (1 year) and death from degenerative brain function loss

*variant Creutzfeldt-Jakob seen in England 
         -1980s: 166 deaths in England, 25 in France
         - same symptoms as typical disease
         - younger
         - no genetic component
        - link to eating beef from BSE infected cows? 
              bone-containing cuts of meat? more likely to have nerve tissue in cut of meat attached to bone
         - link to head injury? 


 *** must cremate bodies as the only way to destroy prions****

Chronic Wasting Disease

* North America prion diseases transmissible to humans
* Mule deer, elk (now some white tail deer) populations
* Squirrel populations? 
***seen when people eat squirrel, some soups use brain to thicken soup***
*** passed by droplets, feces? we don't know

*******************break***********up next bacterial sex*************

 Genetic Variablity

* Essential for natural selection
          - All organisms get random variablity through :Mutations
* Recombination = new combinations of genes in population
          - Eukaryotes: 

•              sex accomplishes reproduction and recombination
•    random assortment of chromosomes during meiosis
•    random gamete fusion
•    random mate choice

 Bacteria separate the two processes: 

•   reproduction (binary fission) = vertical gene transfer
•   cloning = no variability
• 

•   3 processes to accomplish this: conjugation, transformation and transduction
•   recombination (new gene combination is existing cells) = horizontal gene transfer
• 

 Bacteria maximize recombination

* underlying "givens" in how they work:
   - foreign DNA always REPLACES the existing homologous DNA segment.
   - old DNA fragment is RECYCLED (monomers reused)

*** our genomes do NOT do this but bacteria do***

Plasmids move around: 

* plasmid move freely: join and leave both genome and other plasmids.
*plasmid pull out imperfectly, take genes with them to another cell:
      - picture of normal excision, abnormal excision

Transposons: Fig 7.36

* moveable DNA bits change place in genome
a) transposons can jump from one place to another on a DNA molecule
c) transposons can jump to plasmids and be transferred to another cell.

Griffith experiment: transformation

Fig 7.32 smooth and rough pneumococcus bacteria.





Griffith's experiment discovering the "transforming principle" in pneumococcus bacteria.

 
Streptococcus pneumoniae in spinal fluid. FA stain (digitally colored).

*DEAD donor cell: DNA fragments in watery medium.

* Recipient cell must be the SAME SPECIES (unless plasmid absorbed)
    - absorbs RANDOM DNA bits

******(more common in gram negative like E.coli, not all bacteria are capable to do this) ****

* Replacement/ recycling of homologous DNA

draw process.....


 *** chart comparing viral genes**

Transformation:
donor must be dead,
receipent must be same species unless plasmid (r, t or f) ,
No pili needed
No virus required (unless phage killed donor)
receipent: either random genome fragments or plasmid