Announcements 1. Exams are graded - available after class today - in lab. - average = 70%; 105/150 - high score = 97% (only one answer wrong) - low score = - see me (or email) if any questions and if you want to know your point total to date (I have 630 or 732 pts graded so far)
2. Reminder: no labs next week. Chemotaxis lab reports due 12/6. Start soon, so lab is fresh in your mind and you’ll have time to get answers to questions. Work together to do t-tests. Everyone will use same data set.
3. Genetics final exam is Monday, Dec. 9th. If you qualify to reschedule the exam, see me ASAP.
Final is 200 pts of 1000 total pts; 1/2 of final is cumulative.
In the news…..
Titanic accident - April 14, 1912
One unidentified infant - buried in “Titanic grave”
Recently identified - how?
Very small piece of tissue (tooth with piece of root) left in grave - most of body completely decomposed
What technique used to make ID?
Review of lecture 34
Drosophila behavior and genetics
Human behavior and genetics
C. elegans behavior and genetics
Overview of lectures 35/36
I. Genetic approach to study chemotaxis
Paper by Bargmann et al., 1993. Cell 74: 515-527.
Known at start of study:
in vertebrates, olfaction is used to detect presence of any volatile organic molecule and discriminate among different molecules
Odorants bind to receptors in cilia of olfactory neurons and induce a signaling cascade in the cell
Questions: 1. How specific is interaction of odorants and receptors?
2. How many receptors are expressed on a single olfactory neuron?
3. How is information about odorants trnsmitted to brain to generate appropriate behavior?
Approach: determine whether C. elegans is attracted to volatile organic molecules; then screen for mutants that fail to chemotax to particular odorant; characterization of mutants will help address questions and allow for genes involved in process to be identified
Results of Bargmann study
Results, continued from Bargmann study
Is response to volatile chemicals non-specific OR is there a specific chemical recognition of particular odorants?
How to distinguish between these two models?
Use saturation assay - expose worms to uniform concentration of chemical 1; then add point source of chemical 2. If attraction to chemical 2 still occurs, then conclude a specific, saturable process is required for chemotaxis to each chemical.
- 7 classes of volatile organic chemicals that are likely recognized by different receptor proteins
Characterization of odr mutants
Do these “lab behaviors” relate to behavior in wild?
Why does C. elegans chemotax to both water-soluble and organic, volatile chemicals?
- short range to find nearby bacteria (food)
- long range to find more distant food sources
Why does C. elegans avoid certain chemicals?
(ex. high osmolarity solutions)
- they can cause paralysis and death
II. Statistical analysis of chemotaxis data
Is there a significant difference between each index of each unknown and WT?
III. Genetics of Cancer
Is cancer a single disease?
In all cancers, mutations that alter gene expression are seen
Most such mutations are somatic; 1% are germ-line - what is the difference?
Cancer “runs in families” - known for over 200 years
- but no clear-cut pattern of inheritance
- usually one mutant allele of a cancer-causing gene is inherited - predisposes person to cancer
- likelihood cancer develops depends on particular mutant allele, mutations in other genes, and environmental factors
Mutations play a central role in cancer
1) uncontrolled growth 2) metastasis
The “cell cycle”
Many cells alternate between dividing and “resting” or not dividing
Gap 1; metabolic activity and cell growth
1 hour of 16 hour
Gap 2; metabolic activity and cell growth
Three main checkpoints in the cell cycle
genes that regulate the cell cycle
Is cell the correct size?
Is DNA damaged?
2. Is DNA fully replicated?
Is DNA damage repaired?
3. Have spindle fibers formed?
Have they attached to
Why are cell cycle checkpoints important?
What might result if DNA repair has not finished?
Uncontrolled cell division could occur - cancerous cell
Example: p53 protein normally targets cells with severe
DNA damage to undergo programmed cell death.
(this removes them from the population)
If the p53 gene is mutated, damaged cells will not
be removed and may continue dividing in an
Many different types of cancers involve mutations of p53.
Checkpoint Control of Cell Cycle
Retinoblastoma: Familial v. Sporadic
Rb Protein is Inactivated By CDK-Cyclin During G1 S
p53 Gene (tumor suppressor)Normal Functions
Role of p53 in Cell Cycle Control
Breast Cancer Tumor Suppressors
Rous Sarcoma Virus (RSV)
Southern Blots Probed with viral src Gene Revealed Cellular Origin of Oncogenes
Infected chicken #1Infected chicken #2Uninfected chicken
Origin of Transforming Retroviruses
Capsid protein Reverse Transcriptase Envelope Protein
Mutation creates oncogene
Cancers Usually Result from a Series of Mutations in a Single Cell
Tumor Progression: Evolution at the Cellular Level
Benign tumor (polyp in epithelial cells) is confined by basal lamina; then additional mutation occurs.
Malignant tumor (carcinoma in epithelial cells) grows very fast, becomes invasive, and metastasizes.
Cancer Cells Evade Two “Safety” Mechanisms Built into the Cell Cycle
1. Once p53 is inactivated, cells with DNA damage don’t arrest from G1 and don’t undergo apoptosis.
2. Telomerase enzyme is activated, avoiding the limit to cell divisions imposed by telomere shortening.