Unraveling RNA and understanding its role in HIV infection
by Paul Sorenson
Special coverage
From biomedical engineering and medical device development to genetic research
and biological process technology, IT researchers play a major role in the growing
field of biotechnology. Here is a look at 13 of the most innovative projects
underway.
Associate Professor Karin Musier-Forsyth is using her expertise
as a chemist to solve important health-related problems and to understand
some of life's most perplexing biological mysteries.
Armed with a wide variety of chemical and physical tools, Musier-Forsyth
is exploring how proteins and viruses recognize and interact with
ribonucleic acids (RNAs), the complex molecules that translate and
carry out genetic instructions encoded in DNA. Those explorations,
coupled with her interest in health-related issues - led her to
study RNA's role in the life cycle of HIV, the virus that causes
AIDS.
"Because HIV is a retrovirus, its [genetic material] is coded
in RNA, not DNA,” she explains. “When HIV infects a host
cell, its RNA genome has to be converted into DNA. HIV actually
recruits an RNA from the host cell to perform the first step in
that process,” called reverse transcription.
"Why is that specific host RNA used? How is it recruited?
And how does that 'priming' step work? Those are the questions we
hope to answer."
If successful, Musier-Forsyth's research will provide chemical
insights that may lead to new therapeutic approaches for the treatment
of HIV. “If you understand that first step, you can design
inhibitors that may prevent it from happening,” she says.
But new HIV treatments based on this research are a long way down
the road, cautions Musier-Forsyth, and are not a certainty. “First
we have to get an inhibitor to work in a test tube, then we will
have to collaborate [with medical experts] to test it out in vivo,”
she says.
Now in its fourth year, the HIV project has expanded to include
a collaboration with Professor Paul Barbara. “We are on the
verge of making some breakthroughs in this area,” she says.
“It's very exciting."
Musier-Forsyth's research team is also studying how RNAs interact
with amino acids as they assemble protein molecules according to
the instructions encoded in a cell's DNA.
During that process, special enzymes cause a reaction that attaches
specific amino acids to RNA molecules called transfer RNAs that
are encoded to receive them.
"It's essential that each transfer RNA binds with the correct
amino acid,” says Musier-Forsyth. “If the system gets
messed up, then the wrong amino acid is delivered to the site of
protein synthesis, and the cell will die."
To learn more about how amino acids recognize transfer RNAs, Musier-Forsyth
chemically synthesized transfer RNA molecules that were missing
specific atoms and observed how the absence or presence of those
atoms affected enzyme recognition. This research led to the discovery
that, unlike the universal genetic code of DNA, recognition of the
code in transfer RNAs may vary through evolution.
Musier-Forsyth has also detected variations in the transfer RNA
recognition process between bacteria and mammals, a discovery that
may yield important medical benefits.
"Now that we are beginning to understand these species-specific
differences in transfer HIV recognition, we can design inhibitors
that may kill bacteria and leave human cells unaffected,” she
says. “With the recent emergence of antibiotic-resistant microbes,
this approach holds promising new medical potential."
