MOBILE ELEMENTSARE USED AS TOOLS!

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

LTR LTRGENE X

Packaging Signal

10 KB in size

Retroviruses are used for Gene Therapy

Packaging Cells

Gag PolEnv

Non-replication competentvirus containing gene X,pseudotyped with selectedenvelope

polgag envLTR LTR

= Vector

Gene Transfer

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.

Researchers have also successfully used gene therapy to cure hemophilia in mice and dogs

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.

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)

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.

CELL CYCLE

S

M

G2G1

Interphase

Mitotic Phase

S

M

G2G1

Prophase

Prometaphase MetaphaseAnaphase Telophase

Cytokinesis

Gap1cell growthtranscriptiontranslationorganelle synthesis

Gap2cell growthtranscriptiontranslationproduction of proteins for mitosis

DNA Synthesis

S

M

G2G1

CDK4

Cyclin D

CDK2

Cyclin A

CDK2

Cyclin E

INCOMING SIGNAL(Growth Factors)

CDK 1

Cyclin B

S

M

G2G1

DNA is damaged but DNA synthesis proceeds

The cell does not produce enough of the organelles or products needed for DNA synthesis and cell division

DNA is damaged

DNA is not completely synthesized

Cell size is too small for cell division

Sister chromatids do not separate Cell enters cell

cycle when it should not

S

M

G2G1

Critical points in the cell cycle that are tightly regulated.

Checkpoint failures lead to unregulated cell division or cancer.

CELL CYCLE CHECKPOINTS

S

M

G2G1

G1 Checkpoint

cell sizenutrient levelsDNA damage

G2 Checkpoint

cell sizechromosome replicationDNA damage

Metaphase Checkpoint

chromosome attachment to mitotic spindles

Checkpoint failures lead to unregulated cell division or cancer.

S

M

G2G1

CDK4

Cyclin D

E2F

RB

E2FRB

cyclin EE2F

CDK2

Cyclin E

P53

G1 Checkpoint

cell sizenutrient levelsDNA damage

DNA DAMAGE

Apoptosis

Continue

P53 and RB areTUMOR SUPPRESSORS

S

M

G2G1

G2 Checkpoint

cell sizechromosome replicationDNA damage

CDK 1

Cyclin B

Cdc25C

CDK 1

Cyclin B

P53

DNA DAMAGE

cyclin B

CDK1

P21

Incomplete chromosomereplication

S

M

G2G1

Metaphase Checkpoint

chromosome attachment to mitotic spindles

Metaphase Anaphase

Separase

Metaphase

Securin

APC

inactive

APC

active

tension at kinetichore

Cohesin promoteschromosome separation

Mad2

CELL CYCLE IS COMPLEX!THERE ARE MANY INCOMING TRIGGERS

THE DETECTION OF DNA DAMAGE

IS VERY COMPLEX!