Download Matt Reuter

Changing Times, Changing
Paradigms
The “Big News” in Genomics, 2003
Matt Reuter
BL3300, Introduction to Genomics
December 5, 2003
Changing Disciplines



Role of RNA in the Central Dogma of
Molecular Biology
Information Storage in the DNA
Double Helix
Consequences of Mutation and Cancer
RNA Interference

Double-Stranded RNA creates an RISC that
cleaves complementary RNA strands.
microRNA: Introns at Work

Some introns form microRNAs that create
RNA interference, inhibiting other genes.
Active RNA: Antisense

Complementary, “antisense,” RNA blocks
transcription.
Active RNA: Riboswitches and
Ribozymes


RNA can catalyze reactions like enzymes.
RNA can control gene expression through
riboswitches.
DNA: More than ACGT



Chemical additions to the DNA store just as
much information as the sequence.
Epigenome and Epigenetics
Epigenetic information is erased and
rewritten frequently.
Mighty Methylation!


Methyl groups tend to “silence” the DNA,
producing low transcription.
Transposons
Recombining or Imprinting?

Epigenetic inheritance: imprinting.
Epigenetics and Cancer



Less genomic methylation in cancer
cells than normal cells.
More methylation on key cell process
genes.
“Cancer genes” are NOT mutated in
most cancer cells; they are methylated
and epigenetically silenced though.
Cancer: Massive Mutations or
Nuclear Nonsense?



Old Theory: Cancer cells have
mutations to “cancer genes” that cause
cells to reproduce uncontrollably.
New Observation: Cancer cells are
aneuploid.
Most cancer cells would be classified as
a separate SPECIES from the normal
cells.
Is it a bird? A plane? No, it’s
CANCERMAN!

CELLULAR SUPERPOWERS






Ignore “Divide Now” Signals
Ignore Neighbor’s “Stop Dividing”
Signals
Evade Cellular Auto-Destruct
Redirect Blood Flow
Immortalize Genome
Invade Healthy Tissues
Carcinogens and Darwin:
Survival of the Apathetic



“Survival of the Fittest”
Carcinogens speed up mutation rates
Carcinogens damage cells


Normal cells repair
Cancer cells divide

Strength in Numbers
Old Paradigms Yield Control to
New Ideas

Central Dogma of Molecular Biology



Role of RNA
Informational Storage in DNA
Tumor-Suppressor and Oncogene
Theory for the Formation of Tumors.
Want to Know More?





Gibbs, W. Wayt. “Unseen Genome, The: Beyond DNA.”
Scientific American December 2003: 106-113.
Gibbs, W. Wayt. “Unseen Genome, The: Gems Among
the Junk.” Scientific American November 2003: 46-53.
Gibbs, W. Wayt. “Untangling the Roots of Cancer.”
Scientific American July 2003: 56-65.
Lau, Nelson C. and David P. Bartel. “Censors of the
Genome.” Scientific American August 2003: 34-41.
All the other great articles in Scientific American are
highly recommended!