MOBILE ELEMENTS ARE USED AS TOOLS!

1. MOBILE ELEMENTS ARE USED AS TOOLS!

2. MOBILE ELEMENTS ACT AS GENETIC MARKERS IN EVOLUTION STUDIES MOBILE ELEMENTS ARE USED IN FORENSICS ERVs HAVE BEEN USED TO STUDY INFECTIOUS DISEASE AND EMERGING VIRUSES RETROVIRUSES AND DNA TRANSPOSONS ARE USED FOR GENE THERAPY . . . EVEN TO TREAT CANCER

3. gag LTR pol env LTR Retroviruses are used for Gene Therapy Packaging Signal = Vector GENE X LTR LTR 10 KB in size Gag Pol Non-replication competent virus containing gene X, pseudotyped with selected envelope Env Packaging Cells

4. Gene Transfer

5. GENE THERAPY SUCCESSES AND FAILURES SCID is often called "bubble boy disease". SCID became widely known during the 1970's and 80's, when the world learned of David Vetter, a boy with X-linked SCID, who lived for 12 years in a plastic, germ-free bubble. He died after a bone marrow transplant. A recessive disorder of a mutation in the adenosine deaminase (ADA) gene causes SCID. Gene therapy successfully replaced this gene in several ADA patients.

6. Researchers have also successfully used gene therapy to cure hemophilia in mice and dogs Plasmid containing VEGF-2 has been delivered to damaged heart tissue via catheters. VEGF-2 promotes the growth of new blood vessels that are required to provide oxygen-carrying blood to heart muscles to compensate for the blocked heart arteries. Gene therapy has been successfully used to replace p53 in tumor cells or target tumor cells because they lack p53 (Adenovirus used in the later case) SOME FAILURES: In September 1999, 18-year-old Jesse Gelsinger died after being treated for a rare liver disease using a gene carried by a viral gene vector, which was directly blamed for his death. A few patients who were cured of SCID caused by a mutation in the IL2RG gene developed leukemia.

7. CELL CYCLE

8. Mitotic Phase M G2 G1 S Interphase

9. Prometaphase Metaphase Telophase Anaphase M Prophase G2 G1 S Gap2 cell growth transcription translation production of proteins for mitosis Gap1 cell growth transcription translation organelle synthesis DNA Synthesis Cytokinesis

10. INCOMING SIGNAL (Growth Factors) Cyclin B Cyclin D CDK 1 CDK4 M G2 G1 S Cyclin A Cyclin E CDK2 CDK2

11. M G2 G1 S Sister chromatids do not separate Cell enters cell cycle when it should not DNA is damaged Cell size is too small for cell division The cell does not produce enough of the organelles or products needed for DNA synthesis and cell division DNA is not completely synthesized DNA is damaged but DNA synthesis proceeds

12. M G2 G1 S CELL CYCLE CHECKPOINTS Critical points in the cell cycle that are tightly regulated. Checkpoint failures lead to unregulated cell division or cancer.

13. Metaphase Checkpoint chromosome attachment to mitotic spindles G2 Checkpoint cell size chromosome replication DNA damage M G2 G1 S G1 Checkpoint cell size nutrient levels DNA damage Checkpoint failures lead to unregulated cell division or cancer.

14. DNA DAMAGE Apoptosis RB Continue Cyclin D CDK4 M RB G2 E2F E2F G1 G1 Checkpoint cell size nutrient levels DNA damage S E2F cyclin E Cyclin E CDK2 P53 P53 and RB are TUMOR SUPPRESSORS

15. Incomplete chromosome replication Cyclin B Cyclin B CDK 1 CDK 1 Cdc25C M G2 G1 P21 DNA DAMAGE S P53 CDK1 cyclin B G2 Checkpoint cell size chromosome replication DNA damage

16. Metaphase Anaphase M G2 G1 S Metaphase Checkpoint chromosome attachment to mitotic spindles

17. Metaphase Separase Cohesin tension at kinetichore APC APC inactive active Mad2 Securin promotes chromosome separation

18. CELL CYCLE IS COMPLEX! THERE ARE MANY INCOMING TRIGGERS

19. THE DETECTION OF DNA DAMAGE IS VERY COMPLEX!