Transcript 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!