were overlooked for decades, dismissed out of hand as the flotsam
and jetsam of cellular degradation. But over the past few years,
molecular biologists have discovered that the tiny segments of RNA
once thought to be random pieces of genetic material actually do
something—several things, in fact.
Now, Emory genetic researcher Peng
Jin hopes to expand on recent discoveries about the small RNA known
as microRNA (miRNA for short) to develop new diagnostic tests and
possible genetic therapies for brain tumors and neurodegenerative
diseases like Alzheimer’s.
“We are exploring a new frontier
here,” says Jin. “There is a lot still to learn, but
there is enormous potential for helping patients once we better
understand miRNA. This area is so new that the basic work needed
to receive grants from the National Institutes of Health simply
hasn’t been done yet. We are taking a hypothesis-generating
approach. We need to get preliminary data so that we can get NIH
MiRNAs were first described more than
a decade ago by scientists working with Caenorhabditis elegans,
a species of nematode worm favored by researchers because of the
simplicity of its genome. During their normal life cycle, these
worms go through four stages of development. But a particular group
of worms were observed getting stuck in the first stage. The larvae
kept growing larger but not maturing into adults. A team of researchers
at Harvard University isolated the gene that caused this malfunction
but found that instead of coding for a protein as most genes do,
it coded for a particular molecule of RNA.
In typical cell development, double-stranded
DNA is “read” by single-stranded messenger RNA, which
translates (“codes”) the genetic information into proteins
that drive cell development. The nematode discovery showed that
some genes instruct the RNA not to code for proteins, but for other
nontranslating RNA. Small bits of noncoding RNA had been observed
inside cells for years, but scientists thought they were just evidence
of cell aging or environmental damage.
Gradually, different groups of researchers
realized these micro-RNAs play a vital role in cell development.
These short segments interact with the longer strands of messenger
RNA and alter the coding and translation process to influence the
degree to which certain proteins are expressed.
Scientists now believe miRNAs are
a key force controlling gene expression. They are thought to play
a role in determining the differentiation of stem cells into different,
mature cell types, and some researchers belive they influence tissue
development as well.
how they do this, however, is not well understood.
Although more than 1,650 separate
miRNAs have been identified in animal and plant genomes, scientists
have nicknamed them “biological dark matter” because
the way they affect gene expression remains unclear.
A recent Young Investigator award
from California’s Arnold and Mabel Beckman Foundation will
help Jin solve some of these mysteries. The $264,000 awards support
the research of promising young faculty members early in their academic
careers in the chemical and life sciences. Jin was one of only 24
scientists in the country chosen as a recipient, largely because
his work will take miRNA research in a new direction.
“This is one of the hottest
areas of biology,” says geneticist Steve Warren, chair of
the Department of Human Genetics at the School of Medicine. “Only
a handful of labs are currently working on microRNAs, although the
number is growing.”
Jin is the only researcher working
on the relationship between miRNAs and stem cells, and his work
should open up new avenues for further study, Warren says.
“MicroRNAs were only discovered
a few years ago, and it was quite a shock for many scientists that
humans had hundreds of genes, highly conserved throughout evolution,
that do not code for any proteins,” says Warren. “We
still understand very little about their function, particularly
in mammals. Certainly, there are diseases due to or influenced by
defects in the microRNA pathway. It is likely that we’ll find
that microRNAs play a widespread role in disease development, particularly
cancer, and in determining a person’s predisposition to disease.”
Most work in this area is still conducted
on C. elegans and Musca domestica, the common
house fly. But Jin will use his Beckman award to work on a bigger
He plans to expand his work examining the functions of miRNA in
neural stem cells, studying how miRNA influence the generation of
distinct cell types.
“By doing this,” says
Jin, “we hope to establish basic scientific knowledge that
could one day lead to new treatments for neurodegenerative diseases
like Alzheimer’s and Parkinson’s disease.”
Jin hopes to identify more of the
unknown types of miRNA in neural stem cells to broaden the picture
of how they function. Emory researchers are interested in more than
just chronicling the molecules’ function, however. Genetics
faculty are working with scientists at the Winship Cancer Institute
to study brain tumors and leukemia. They plan to develop new genetic
tools for cancer diagnosis by finding genetic biomarkers linked
to development of these diseases.
“Published genetic data from
different types of breast tumors, for example, show that a certain
microRNA is either overexpressed or underexpressed in particular
developmental paths of tumors,” Jin says. “We hope to
take that a step further. Using our technology, we can compare different
types of brain tumors and identify whether a particular microRNA
is either overexpressed or underexpressed. This ability could lead
to finding biomarkers for diagnosis.”
One day, scientists may also be able
to manipulate miRNA to treat such diseases and genetic conditions
and not just diagnose them earlier, Jin says.
For example, scientists could try
to suppress the growth of tumors either by knocking down or overexpressing
certain miRNA. “That’s way down the road, but that’s
where this work with microRNA may lead,” says Jin. “In
the long run, it could have a huge impact on therapies for a variety
of cancers and neurodegenerative diseases.”
It is this potential that has kept
Jin at Emory and pursuing this difficult area of study. Opportunities
to collaborate with clinicians and one day see his research save
lives are his primary motivators, he says. “There are opportunities
here for geneticists to have a clinical impact that simply do not
“Here we have the research tools
to connect basic science with real people,” Jin says. “I
want my work to help real people, and I hope to see the result of
my work during my lifetime—not just for the sake of discovery.
I want to make a difference.”
Gregg is a freelance writer based in Atlanta.