The 1966 science fiction movie called Fantastic Voyage presented a miniaturized
submarine that traveled through the bloodstream to prevent a clot from causing a
stroke. Scientists hope that someday day in the distant future, intelligent
miniature computers will roam our bodies, detecting early stage diseases and
treating them on the spot by releasing a suitable drug, without any outside
help. To make this vision a reality, computers must be sufficiently small to fit
into body cells and be able to “talk” to various cellular systems. These
challenges can be best addressed by creating computers based on biological
molecules such as DNA or proteins.
The idea is far from
After all, biological organisms are capable of receiving and
processing information, and of responding accordingly, in a way that resembles a
computer. Now Weizmann Institute of Science researchers have made an important
step in this direction: They have succeeded in creating a genetic device that
operates independently in bacterial cells. The device has been programmed to
identify certain parameters and mount an appropriate response.
searches for transcription factors – proteins that control the expression of
genes in the cell. A malfunction of these molecules can disrupt gene expression.
In cancer cells, for example, the transcription factors regulating cell growth
and division do not function properly, leading to increased cell division and
the formation of a tumor. The device, composed of a DNA sequence inserted into a
bacterium, performs a “roll call” of transcription factors. If the results match
pre-programmed parameters, it responds by creating a protein that emits green
light – supplying a visible “positive” diagnosis.
In follow-up research,
the scientists, Prof. Ehud Shapiro and Dr. Tom Ran of the departments of
biological chemistry and computer science and of applied mathematics, plan to
replace the light-emitting protein with one that will affect the cell’s fate,
for example, a protein that can cause the cell to commit suicide. In this
manner, the device will cause only “positively” diagnosed cells to
In the present study, published in Nature’s Scientific
Reports, the researchers first created a device that functioned like what is
known in computing as a NOR logic gate: It was programmed to check for the
presence of two transcription factors and respond by emitting a green light only
if both were missing.
When the scientists inserted the device into four
types of genetically engineered bacteria – those making both transcription
factors, those making none of the transcription factors, and two types making
one of the transcription factors each – only the appropriate bacteria shone
green. Next, the research team – which also included graduate students Yehonatan
Douek and Lilach Milo – created more complex genetic devices, corresponding to
additional logical gates.
Following the success of the study in bacterial
cells, the researchers are planning to test ways of recruiting such bacteria as
an efficient system to be conveniently inserted into the human body for medical
purposes (which shouldn’t be a problem; recent research reveals there are
already 10 times more bacterial cells in the human body than human cells). Yet
another research goal is to operate a similar system inside human cells, which
are much more complex than bacteria.
As half of all
cases of hearing loss are not due to environmental causes but rather to genetic
mutations, it isn’t surprising that advanced gene research is increasingly being
used to learn more about the gene-deafness connection. Now Prof. Karen Avraham
of Tel Aviv University’s Sackler Faculty of Medicine at Tel Aviv University has
discovered a significant mutation in a LINC family protein — part of the cells
of the inner ear— that she believes could lead to new treatments for hearing
The discovery was recently reported in the Journal of Clinical
Her team of researchers, including Dr. Henning Horn and
Profs. Colin Stewart and Brian Burke of Singapore Institute of Medical Biology,
discovered that the mutation causes chaos in a cell’s anatomy. The cell nucleus,
which contains our entire DNA, moves to the top of the cell rather than being
anchored to its normal place at the bottom. Though this has little impact on the
functioning of most of the body’s cells, it is devastating for the cells
responsible for hearing, explains Avraham.
“The position of the nucleus
is important for receiving the electrical signals that determine proper
Without the ability to receive these signals correctly, the
entire cascade of hearing fails.”
This discovery, she says, may be a
starting point for the development of new therapies. In the meantime, the
research could lead toward work on a drug that is able to mimic the mutated
protein’s anchoring function, which could potentially restore hearing in some
The TAU geneticist originally uncovered the mutation while
attempting to explain the cause of deafness in two families of Iraqi- Jewish
descent. For generations, members of these families had been suffering from
hearing loss, but the cause remained a mystery.
Using genetic sequencing,
she discovered that the hearing impaired members of both families had a mutated
version of the protein Nesprin4, a part of the LINC group of proteins that links
the cell’s nucleus to the inner wall of the cell.
Avraham recreated this
phenomenon in her lab by engineering the mutation in single cells. With the
mutation in place, Nesprin4 was not found in the area around the cell nucleus,
as in healthy cells, but was spread throughout the entire
Investigating further, she studied lab mice that were engineered to
be completely devoid of the protein.
Created in Singapore, the mice were
originally engineered to study the biology of LINC proteins. The fact that they
were deaf came as a complete surprise to researchers.
protein serving as an anchor, the cell nucleus is not located in the correct
position within inner ear cells, but seems to float throughout. This causes the
cells’ other components to reorient as well, ultimately harming the polarity of
the cells and hindering electrical signals.
It’s a mutation that took a
heavy toll on the cells’ ability to transfer sound signals, causing the mice to
be born deaf. Given the similarity between mouse and human inner ear cells,
researchers predict that the same phenomenon is occurring in human patients with
a mutation in the Nesprin4 gene.
Avraham says that she and her
collaborators are the first to reveal this mutation as a cause of
“Now that we have reported it, scientists around the world can
test for mutations in this gene,” she suggests.
The mutation could indeed
be a more common genetic cause of deafness in a number of
And because Nesprin4 belongs to a family of proteins that
have been linked to other diseases, such as muscular coordination and
degeneration disorders, this could prove a ripe area for further
MIGRAINE TRIGGERS NOT SO STRONG
A new study suggests that
triggers for migraine with auras may not be as strong as some people think. The
research was just published in the online issue of the journal
Auras that occur with migraine include visual disturbances,
with symptoms such as flashing lights or wavy lines.
According to Dr.
Mark Green, director of the Center for Headache and Pain Medicine at Mount Sinai
Hospital in New York, these results are not a surprise. Although occasionally
dietary management can be helpful, he has for years not recommended routine use
of strict anti-migraine diets, which were very burdensome to patients and produce
minimum benefits. Some “triggers” like chocolate are probably not triggers at
all but rather a neurobiological craving that is associated with the migraine
attack, rather than causing the attack.
Furthermore, triggers are likely
to be additive and are a “perfect storm” when they trigger an attack.
example, in women before their menstrual periods, triggers may become relevant,
whereas at other times of the month, they are harmless.
It is important
to remember that triggers are just triggers; not the cause; those with migraine
may just have a somewhat increased susceptibility, which might be genetically driven.