Vol. 02 NO 6
NEWS - PAGE 2
MUTATIONAL TRIGGER TO IMMUNE
DISEASES IDENTIFIED
BUDGET SPECIAL
PM Research Fellowship of Rs
1,800 Crore To be Launched |
Here is What You Should Know !
Now, the Modi Administration’s 2018
budget proposal, announced with great re-
spect to this fact has allocated Rs 1,800 crore
under the Prime Minister Research Fellow-
ship (PMRF) scheme for BTech students
working towards their PhDs in premier in-
stitutes. The Centre will provide Rs.75,000
as monthly fellowship to those researchers
doing their PhDs in Indian Institutes of Tech-
nology (IITs) or Indian Institute of Science
(IISc).
“The government has … launched a Prime
Minister Research Fellows scheme this
year… Under this scheme, we will identify
1,000 best B.Tech students each year from
premier institutions and provide them facil-
ities to do PhDs in the Indian Institutes of
Technology (IITs) and the Indian Institute
of Science (IISc)… The students will also
be rewarded with a handsome fellowship
amount,” Union finance minister Arun Jait-
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NEWS - PAGE 4
PROTEIN COMBO FOUND TO EXERT
REGENERATING EFFECT
IN PARKINSON’S
ley said while presenting the Union Budget.
The government has also taken steps to “set
up a specialised railway university in Va-
dodara” and “two new full fledged schools
of planning and architecture. Additionally,
18 School of Planning and Architecture will
be set up in IITs and NITs as autonomous
schools,” the central minister said.
Calling the year’s budget “world’s largest
healthcare program”, Mr. Jaitley has also
announced extensive healthcare schemes for
the vulnerable. “We are slowly progressing
towards universal health coverage,” he said
in his speech.
Regarding the PMRF, around 1000 students
will be selected every year for the fellowship
for three years and the stipend of Rs.75, 000
per month will be paid for five years. The
ministry will reportedly be granting scholar-
February 6th, 2018.
NEWS - PAGE 8 NEWS - PAGE 10
PREVIOUSLY UNKNOWN, BACTERIA-HUNTING BOOSTING OESTROGEN
MARINE VIRUSES DISCOVERED ACTIVITY GIVES HOPE OF NEW NEURO-
BLASTOMA TREATMENT POSSIBILITIES
PM Research
Fellowship
of Rs 1,800 Crore
India is a country with tens of top class
research institutions in the basic scienc-
es and in the medical and engineering
sciences. The combined strength of jun-
ior researchers from all these institutions
will run into the ten thousands.
By Disha Padmanabha
ship to 3,000 students in total. the undergraduate students in taking up re-
The fellowship is applicable to the students
of IIT, NIT, IISc and IIIT (students from the
search, the fellowship will also address the
problem of faculty deficit. IITs are finding it
other institutes can apply for the fellowship
but will have to pursue research in IITs only).
The applicants should ideally score high in
difficult to have pool of good brains that will
step up to the faculty in the future. Over a
period of time, we will be able to build a pool
their programs or courses (above 8 CGPA),
have a strong academic background and
of good caliber researchers and it will make
a big difference on faculty recruitment.”
should be from the above mentioned insti-
tutes.
Using this attempt to woo students as a back-
drop, the finance minister in his Budget 2018
presentation talked about how the PMRF will
help identify bright students pursuing BTech
in premiere engineering institutes and they
will be provided higher-education opportu-
nities in IITs IISc Bangalore with handsome
financial assistance.
The development follows closely on the
heels of students at IITs stopping to go
abroad for higher education in large num-
bers as compared to trend of last few dec-
ades. They now stay back and around 10%
to 15% go abroad and that too preferably for
jobs rather than higher education. “So what
will happen, we need to find faculty for them
and research areas,” said a source from IIT
Delhi to NEWS18.
The source added, “The idea was proposed
some time back – apart from encouraging
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1
February 6th, 2018.
MUTATIONAL TRIGGER TO IMMUNE DISEASES
IDENTIFIED
GTPase of immunity-associated protein 5
(Gimap5) is linked with lymphocyte surviv-
al, immune homeostasis, and (auto)immune
disease. Gimap proteins are predominantly
expressed in lymphocytes and regulate lym-
phocyte survival during development, selec-
tion, and homeostasis. Specifically, polymor-
phisms in human GIMAP5 are associated
with increased risk of islet autoimmunity in
type 1 diabetes (T1D), systemic lupus erythe-
matosus (SLE), and asthma.
Members of this family share a GTP-bind-
ing AIG1 homology domain and seem to be
localized to different subcellular compart-
ments, with Gimap5 localizing in multivesic-
ular bodies (MVB) and lysosomes. Overall,
a function for Gimaps in maintaining T cell
homeostasis is not clearly defined.
Now, an international group of scientists
have discovered how a gene mutation af-
fects T cell function to promote immune dis-
orders and then tested a treatment based on
the discovery—successfully fixing donated
immune cells from a 16-year-old boy with
an abnormally low level of white blood cells
called lymphopenia.
“Our data suggest GSK3 inhibitors will im-
prove T-cell survival and function and may
prevent or correct immune-related disorders
in people with Gimap5 loss-of-function mu-
tations,” said Dr. Hoebe, Ph.D., who is at
the division of immunobiology. “Therapeuti-
cally targeting this pathway may be relevant
for treating people with Gimap5 mutations
linked to autoimmunity in type 1 diabetes
(T1D), systemic lupus erythematosus (SLE),
or asthma.”
Immune system disorders lead to abnormal-
ly low immune activity (deficiency) or over-
2
Vol. 02 NO 6
By Disha Padmanabha
activity (autoimmunity). Immune deficiency nodeficient patients that have GIMAP5 LOF research will be needed before their find-
diseases decrease the body’s ability to fight [loss of function] mutations.…We posit that ings can be translated into the clinic. Nev-
infection, while autoimmunity prompts the GSK3-inhibitors will improve overall T-cell ertheless, Hoebe says, “We believe the use of
body to attack its own tissues. Both are com- survival and function and may prevent/cor- GSK3 inhibitors to prevent or correct these
mon causes of illness, and malfunctioning T rect immune- associated sequelae observed type of immune-related diseases holds great
cells are linked to both. in these patients.” potential.“
Despite the critical role of Gimap5 in im- The researchers acknowledge that further
mune cell function, the mechanism(s) under-
lying its activity haven’t yet been identified.
The Cincinnati team has now shown that
Gimap5 is a critical inhibitor of GSK3β in
both human and mouse CD4+ cells.
If GSK3 isn’t inactivated—due to lack of
Gimap5 function—it causes DNA damage in
expanding T cells, which affects T-cell func-
tion and survival. The researchers’ studies
showed that targeting GSK3β in the T cells
of Gimap5-deficient mice led to improved
T-cell survival, prevented liver damage and
the development of colitis.
“Our studies reveal a key role for Gimap5
in inactivating GSK3β during CD4+ T cell
activation, a link that is critically required
to maintain T cell fitness and allows for pro-
ductive T cell proliferation. We propose that
the Gimap5- mediated inactivation of GSK3β
is an essential molecular mechanism to sup-
port productive CD4+ T cell responses.”
They claim that their results point to a “re-
markable therapeutic potential” for the use
of GSK3 inhibitors to improve CD4+ T-cell
survival and proliferation and to prevent im-
munopathology.
This confocal microscopic image of a healthy mouse T cell uses color florescence to il-
GSK3 inhibitors have already been used to lustrate how the protein Gimap5 (upper-right faint-green area) and the enzyme GSK3
treat disease, including Alzheimer’s disease, (red) overlap in small structures called vesicles inside cells (colocalized-yellow area). This
mood disorder, cancer, and diabetes mel- happens before GSK3 enters the cell nucleus (shown in blue). This step is important to
litis, they note. “Our current data reveal a limit DNA damage in active T cells during their expansion. The image is part of a study
new therapeutic application of GSK3 inhib- published Jan. 30 by Nature Communications from researchers at Cincinnati Children’s.
itors specifically in the treatment of immu-
Vol. 02 NO 6
World’s First Ear Implants
Crafted Via One’s Own
Cells Using 3D Printing
Chinese researchers grow new ears for five
children suffering from microtia using their
own cells with the help of 3D scanning and
3D printing.
Microtia is a congenital malformation of
the external ear, with a varied regional prev-
alence rate of 0.83 to 17.4 per 10,000 births
worldwide, and higher prevalence rates in
Hispanics and Asians. The external part of
the ear or the auricle is an important identi-
fying feature of human face, and hence its
deformity has a profound effect on self-confi-
dence and psychological development in the
afflicted children.
Current cosmetic procedures of treating mi-
crotia mainly include the wear of auricular
prosthesis, implantation of non-absorbable
auricular frame materials or an autologous
rib cartilage framework. Non-absorbable
frames, such as silastic or high-density pol-
yethylene, generate an excellent ear shape
without donor site morbidity, but they lack
bioactivity and can lead to extrusion and in-
fections.
But now, in a work that’s the first study of
its kind, Chinese scientists have engineered
a patient-specific ear-shaped cartilage in vit-
ro using a 3D printed biodegradable scaffold
and Microtia Chondrocyte (MCs) cartilage
cells.
“We were able to successfully design, fabri-
cate, and regenerate patient-specific external
Scientists Design Drug to
Control Premature
Differentiation
of Stem Cells
“Stem cells are like flour – they can be
baked into any number of things like pies,
cookies or bread – but once that happens,
there is no going back to flour,” says senior
author Fabio Rossi, Professor of Medical
Genetics at UBC’s Biomedical Research Cen-
tre and the new UBC School of Biomedical
Engineering. “The problem was that all our
stem cells were turning into ‘bread’ and we
really needed them to stay as ‘flour’ so they
could continue to replicate, creating enough
cells so that we can transplant and regener-
ate the tissue effectively.”
“Stem cells are like flour – they can be
baked into any number of things like pies,
cookies or bread – but once that happens,
there is no going back to flour,” says senior
author Fabio Rossi, Professor of Medical
Genetics at UBC’s Biomedical Research Cen-
tre and the new UBC School of Biomedical
Engineering. “The problem was that all our
stem cells were turning into ‘bread’ and we
really needed them to stay as ‘flour’ so they
could continue to replicate, creating enough
cells so that we can transplant and regener-
ate the tissue effectively.”
The team of collaborators identified a pro-
February 6th, 2018.
ears,” the researchers wrote in their study,
which followed each child for up to 2½ years.
“Nevertheless, further efforts remain nec-
essary to eventually translate this prototype
work into routine clinical practices,” they
wrote. “In the future, long-term (up to 5
years) follow-up of the cartilage properties
and clinical outcomes … will be essential.”
The project was started off with a scan of
the healthy ear and a digital image of it creat-
ed using 3DPRO software. This digital image
was then symmetrically mirrored to guide re-
construction. A corresponding resin model of
this mirrored ear was 3D printed on a Z Corp
Spectrum 510 3D printer, a model that first
shipped in 2005 by the company who would
later be acquired by 3D Systems in 2012.
The 3D printed model was used to cast a
pair of molds from clay and silicone, which
By Disha Padmanabha
could then hold biomaterial scaffolds. To
produce the biodegradable biomaterial scaf- The cartilage ear was surgically implanted healthily shaped.
folds, a 9 square centimeter inner PCL mesh in a similar way to rib cartilage. The child’s
with three square milimeter grids and a thick- skin was draped over the cartilage and it fit “This work clearly shows tissue engineer-
ness of 1.37 mm was 3D printed. the new shape of the ear thanks to vacuum ing approaches for reconstruction of the ear
This inner core was wrapped with PGA un- drainage. and other cartilaginous tissues will become a
woven fibers and coated with PLA. Expanded Now, the researchers have over two years of clinical reality very soon,” Cornell Univer-
MCs harvested from the child’s microtic ear. follow-up data and the results are promising. sity biomedical engineering Professor Law-
These were evenly dropped onto the PGA/ None of the children rejected the new ears, rence Bonassar told CNN. “The aesthetics of
PLA layer of the ear-shaped scaffold and then four of the five ears developed cartilage af- the tissue produced are on par with what can
placed in a cell culture solution. The cartilage ter the implantation and though two showed be expected of the best clinical procedures at
ear was removed after twelve weeks. slight distortion after the surgery, three were the present time.“
tein known as Setd7 that plays a role in con-
trolling stem cell growth and their maturation
into muscle fibres. Using a drug co-devel-
oped by Rossi, the researchers were able to
inhibit the Setd7 protein to prevent the stem
cells from differentiating so they could con-
tinue to divide. They then implanted these
stem cells into the hind leg of mice affect-
ed by a mouse-model of muscular dystrophy By Disha Padmanabha
and found that the cells fused to the mus-
cle, regenerated the tissue and improved the L-R: Robert Judson and Fabio Rossi.
strength of the muscle.
“This discovery unveils a new method to
boost the therapeutic potential of muscle stem
cells, allowing these cells, when transplanted
into damaged tissue, to facilitate tissue re-
generation and improve muscle function,”
said Robert Judson, postdoctoral fellow at
UBC, senior scientist at STEMCELL technol-
ogies and lead author of the paper.
3
February 6th, 2018.
Protein Combo Found to
Exert Regenerating Effect
in Parkinson’s
Alzheimer‘s disease and Parkinson’s dis-
ease are the most common neurodegenerative
diseases worldwide. Despite all the efforts
made by the scientific community, current
available treatments have limited effective-
ness, without halting the progression of the
disease.
Parkinson’s is a motor neuron disorder
characterised by a loss of dopaminergic
neurons in the substantia nigra of the brain.
These nerve cells are found in the black sub-
stance of the brain, where they produce the
neurotransmitter dopamine, a key modulator
of involuntary movement.
Two factors; Vascular Endothelial Growth
Factor (VEGF) and Glial Cell-derived Neu-
rotrophic Factor (GDNF), are proteins that
play an essential role in nerve cell function
by inducing cell growth, plasticity and sur-
vival.
Now, scientists at the University of the
Basque Country have found that these two
neurotrophic factors work in synergy to ben-
efit patients with early-stage Parkinson’s dis-
ease.
The results showed that the changes caused
by the condition were not homogeneous in
the different parts of the brain affected. “The
impairment is correlated with the specific
anatomic distribution of the dopaminergic
neurons and their terminals,” pointed out the
researcher Catalina Requejo.
In the course of the study, therapeutic strate-
gies based on the release of neurotrophic fac-
tors were applied. Since these factors encour-
age cell growth, plasticity and survival, they
therefore play an essential role in controlling
neuronal function.
The Vascular Endothelial Growth Factor
(VEGF) and the Glial Cell-derived Neuro-
Lysosomes and
Mitochondria Catch up on
Regulation in Cell
In the latest scoop, scientists chanced upon
the two key cellular structures, mitochondria
and lysosome getting in “touch” to exchange
regulatory tips with respect to their respec-
tive cellular functions.
Both mitochondria and lysosomes are es-
sential for maintaining cellular homeostasis,
and dysfunction of both organelles has been
observed in multiple diseases.
Mitochondria are highly dynamic and un-
dergo fission and fusion to maintain a func-
tional mitochondrial network, which drives
cellular metabolism. Similarly, lysosomes
undergo constant dynamic regulation by the
RAB7 GTPase, which cycles from an active
GTP-bound state into an inactive GDP-bound
state upon GTP hydrolysis.
This rare discovery has implications for the
research of many diseases, including Parkin-
son’s and cancer, as well as for the under-
standing of normal aging.
4
Vol. 02 NO 6
trophic Factor (GDNF) were delivered en-
capsulated in microspheres or in nanospheres,
even smaller than the former, comprising a
biocompatible, biodegradable polymer: Poly
Lactic-co-glycolic Acid (PLGA), which al-
lows them to be released continuously and
gradually. Furthermore, the factors were ad-
ministered in a combined way to determine
whether, together, they induced a synergistic
effect.
The results were encouraging in both the
early and severe phase of the model. The
combining of the VEGF and GDNF not only
significantly reduced the degeneration of the
dopaminergic neurons of the black substance,
it also induced the formation of new cells and
cellular differentiation.
“The consequences for the dopaminergic
system were even worse, which supports the
beneficial synergistic effects exerted by the
VEFG and the GDNF in Parkinson’s,” con-
cluded the researcher.
These Spanish researchers have opened the
door on a new approach to the treatment of By Disha Padmanabha
Parkinson’s disease, a neurodegenerative dis-
ease that, along with Alzheimers and ALS, is
proving a massive challenge for biotech and
pharma alike.A
“In some ways, we assume that scientists
have discovered all the major inner workings By Disha Padmanabha
of our cells in the 21st century. And yet in
nisms] of various human diseases,” said first ulated by a lysosomal protein called RAB7.
this work, we made a new observation that
author Yvette Wong, a postdoctoral fellow in The scientists are now investigating how
these two organelles are directly talking to
Krainc’s laboratory. dysfunction of the proteins that tether mito-
each other,” said principal investigator Dr.
chondria and lysosomes together may affect
Dimitri Krainc, the Aaron Montgomery Ward
Krainc’s laboratory had previously identi- the function of the organelles, as mutations
Professor and chair of the Ken and Ruth
fied a functional link between mitochondri- in some of these proteins have already been
Davee Department of Neurology at North-
al and lysosomal dysfunction in Parkinson’s implicated in neurological diseases.
western University Feinberg School of Med-
disease, but this study, however, is the first to
icine. “It’s a surprising finding that provides
identify direct physical contact between the “It’s very important that we now know that
new insights into normal cell function and
two organelles. these organelles are talking to each other di-
will likely have implications for a number of
The team used video microscopy with rectly. How exactly these contacts are disrupt-
diseases across the board.”
fluorescent tagging of the two organelles, ed in various diseases, including Parkinson’s,
to observe that the mitochondria and lyso- and how to restore them therapeutically, will
“The discovery of these mitochondria-lyso-
somes formed stable contacts inside living be the subject of in-depth investigations in
some contacts is extremely exciting. We now
human cells. The authors also employed oth- the future,” said Krainc, also director of
show that these contacts offer a potential
er advanced imaging techniques- including the Center for Neurogenetics, a professor of
site through which mitochondria and lys-
electron microscopy and super-resolution neurological surgery and physiology at Fein-
osomes can crosstalk, and it suggests that
imaging- to discover that the formation and berg, and a professor of neurobiology at the
defects in the regulation of this contact site
subsequent loosening of these contacts is reg- Weinberg College of Arts and Sciences.
may drive the pathogenesis [disease mecha-
Vol. 02 NO 6
PREVIOUSLY UNKNOWN, BACTERIA-HUNTING
MARINE VIRUSES DISCOVERED
“The recovery of the non-tailed autolyki-
viruses represents a first step in revealing
extensive missed diversity in one of the two
major ancient lineages of dsDNA bacterial
viruses, and suggests that their ecological
and evolutionary importance for microbial
systems is far greater than is currently recog-
nized,” co-senior authors Martin Polz, a civil
and environmental engineering researcher at
MIT, and Libusha Kelly, a systems and com-
putational biology researcher at Albert Ein-
stein College.
By profiling tail-less, double-stranded DNA
(dsDNA) viruses from bacteria in ocean sam-
ples, researchers from Massachusetts Insti-
tute of Technology and Albert Einstein Col-
lege of Medicine have identified a previously
unappreciated family of autolykiviruses ca-
pable of killing marine bacteria.
About 10 million viruses (not all of them
infect bacteria) are found in every millimeter
of sea surface water, and they play a largely
unsung role in the marine food chain, study
lead author Kathryn Kauffman.
This previously unknown, recently de-
scribed virus family is particularly adept at
preying on and infecting marine microbes,
helping to maintain a healthy balance in
ocean ecosystems. In a single day, viruses kill
an estimated 20 percent of the ocean’s prolif-
ic bacteria, “releasing nutrients for survivors
and re-routing the flow of materials between
players and places on global scales,” Kauff-
man said.
The team calls their discovery Autolyki-
viridae, after Autolykos (“the wolf itself”):
a character from Greek mythology, who as a
trickster and thief proved similarly tricky to
catch.
But Autolykiviridae has been caught, and
now that we know about it, the discovery is
helping scientists to fill in a large missing
link in virus evolution.
The genomes of this new family are very
short compared to tailed viruses, composed
of about 10,000 bases, instead of the typical
40,000–50,000 for tailed viruses.
The tail-less viruses look to be representa-
tives of an ancient viral lineage defined by
specific types of capsids, the protein shell
that encases viral DNA — which we knew
commonly infects animals and single-celled
organisms, but not bacteria.
“We already knew that viruses are very im-
portant there,” Kauffman says, referring to
the surface ocean, where the researchers’
samples were drawn, and where about 10
million viruses are found in every milliliter
of water. Polz says that while “most of the vi-
ruses studied in labs have tails, most of those
in the ocean don’t.” So the team decided to
study one subset of tailless viruses, which
infects a group of bacteria called Vibrio. Af-
ter extensive tests, they found “that some of
these were infecting unusually large numbers
of hosts,” he says.
The team states that, typically the way re-
searchers test for viral activity is by infect-
ing bacteria with the viral sample and then
checking the samples a day later to look for
signs that patches of the bacteria have been
killed off. But these particular nontailed vi-
ruses often act more slowly, and the killed-
off regions don’t show up until several days
have passed — so their presence was never
noticed in most studies.
Another important aspect of these findings
is that the Autolykiviridae were shown to be
members of an ancient viral lineage that is
defined by specific types of capsids, the pro-
tein shell encasing the viral DNA. Though
this lineage is known to be very diverse in
animals and protists — and includes viruses
such as the adenoviruses that infect humans,
and the giant viruses that infect algae — very
few viruses of this kind have been found to
infect bacteria.
“This work substantially changes the ex-
isting ideas on the composition of the ocean
virome by showing that the content of small,
tailless viruses … is comparable to that of the
tailed viruses … that are currently thought to
dominate the virosphere,” says Eugene V.
Koonin, a senior investigator at the National
Institutes of Health, who was not involved in
Electron microscope images of marine bacteria infected with the non-tailed viruses stud-
ied in this research. The bacterial cell walls are seen as long double lines, and the viruses
are the small round objects with dark centers.
Courtesy of researchers
February 6th, 2018.
By Disha Padmanabha
this research. “This work is important also
for understanding the evolution of the virus
world because it shows that viruses related
to the most common viruses of eukaryotes
(such as adenoviruses, poxviruses, and oth-
ers), at least in terms of the capsid structure,
are much wider-spread in prokaryotes than
previously suspected.”
Koonin adds, “I further wonder whether
the viruses reported here might only rep-
resent the tip of the proverbial iceberg, be-
cause capsid proteins can be highly diverged
in sequence so that many are missed even in
sensitive database searches. The findings are
also of practical importance because the tail-
less viruses appear to play a major ecologi-
cal role in the ocean, being responsible for a
substantial fraction of bacteria-killing.”
5
February 6th, 2018.
The Saviour Returns :
Long-Abandoned
Antibiotic Makes
Come-back to Battle
Superbugs
Over-reliance on and misuse of antibiotics
has led to warnings of a future without effec-
tive medicines.
Scientists are presently searching for new
drugs, antibiotics; testing microbes in sourc-
es as diverse as soil, saves and amphibian
blood in addition to trying to develop new,
lab-made synthetic antibiotics. All in pursuit
of better new and better antibiotics.
Yet, despite all these remarkable advances,
we are running out of effective antibiotics-
the drugs that fight infection and are essential
for everything from organ transplants to the
treatment of food poisoning.
Therefore, scientists have now found and
re-enlisted a retired antibiotic to come back
and save us all.
Octapeptin was discovered 40 years ago
but was largely unused since, forgotten by
scientists as other drugs took priority. Re-
searchers from the University of Queensland
in Australia have now re-analyzed this old
and largely forgotten antibiotic and believe
the drug could potentially take on resilient
superbugs.
Mining Bitcoin
from DNA : Belgian
Student Earns a Bitcoin by
Cracking DNA Puzzle
A self-confessed “DNA Junkie”, Sander
Wuyts, a Ph.D. student from the University
of Antwerp (UAntwerp) and Vrije Univer-
siteit Brussel (VUB), has won one bitcoin,
worth over $10,000 by decrypting a DNA
sequence.
Nick Goldman is a well-known British sci-
entist specialising in DNA and the ability to
store data in it. In January 2015, the Europe-
an Bioinformatics Institute professor, gave a
presentation on the subject at the prestigious
World Economic Forum in Davos.
“DNA is a really good way of storing in-
formation,” Goldman explained. “Unlike a
memory stick, for example, DNA lasts for a
long time, long after the death of the ‘own-
er’. It’s also very compact: you can store an
incredible amount of information in a minus-
cule space.”
On the same platform, a challenge was pro-
posed- to decode a DNA sequence in order
to gain access to a key that would unlock a
digital wallet, with a three-year time limit.
Goldman’s challenge was set to expire on
January 21, 2018. If no one had successfully
sequenced a DNA sample by that time, the
6
Vol. 02 NO 6
“Octapeptins were discovered in the late
1970s but were not selected for develop-
ment at the time, as there was an abundance
of new antibiotics with thousands of people
working in antibiotic research and devel-
opment,” says one of the researchers, Matt
Cooper from the University of Queensland in
Australia.
“Given the very few researchers left in this
field now, and the sparse pipeline for new an-
tibiotics, we’ve used modern drug discovery By Disha Padmanabha
procedures to re-evaluate its effectiveness
against superbugs.” “The emergence of resistance to merope- years. As such, the University of Queensland
nem, and now colistin, the antibiotic of last researchers are hoping that by re-analyzing
Professor Cooper said there were no new resort, means multi-drug and extensively the older antibiotic and introducing it as a
classes of antibiotics available for Gram-neg- drug-resistant bacteria are now a reality con- superior alternative once colistin fails, they
ative bacteria, with increasing incidence of fronting clinicians. Octapeptin showed supe- will at least have provided another weapon in
extensive drug resistance around the world. rior antimicrobial activity to colistin against our arsenal; potentially, a very powerful one.
Gram-negative bacteria are harder to kill as extensively resistant Gram-negative bacteria
disease organisms, because they have an ex- in early pre-clinical testing. In addition, oc- The team’s creative solution could also in-
tra membrane to penetrate that is often hid- tapeptin was shown to be potentially less tox- spire other research that looks to repurpose
den by a capsule or slime layer which acts ic to the kidneys than colistin” he said. old, forgotten about drugs — or even create
to camouflage them from drugs and our im- brand new ones — that could be stockpiled
mune system. Despite urgent circumstances, only one new for the ongoing fight against antibiotic resist-
class of antibiotic has emerged in the past 30 ance.
Bitcoin reward would have become moot.
With the deadline coming up, Goldman sent
out a reminder on Twitter as no person who
had obtained the tube of DNA, presumably
had been able to crack the code. This tweet
caught the attention of Wuyts, who request-
ed a DNA sample from Goldman and spent
the last month working with his colleagues at
school to crack the code.
By Disha Padmanabha
“When I read the tweet, it goes without say-
ing that I was extremely enthusiastic,” Wuyts
wrote on his blog. “I still remember myself Sander Wuyts (UAntwerp and VUB)
announcing to all of my colleagues that we
should drop everything we’re doing and start Joyce. the money, I can thank the colleagues who
solving this challenge.” helped me and celebrate my PhD in style,”
“To be honest, I had my doubts about the he concludes.
Working alongside his colleagues, the com- feasibility of using DNA to store data and this
putational microbiology student used the ge- challenge changed that — Now I know very Meanwhile, the fact that the key was suc-
nome sequencing tools available via his uni- well that this new technology offers great op- cessfully decoded demonstrates how DNA
versity to make a play for the prize. As luck portunities, maybe even for my own future storage might be used to great effect. Accord-
would have it, he was able to successfully research,” Wuyts says. ing to Goldman, it’s a particularly safe way
decrypt the three-year old Bitcoin puzzle just to store keys since not everyone has access
five days before it was due to expire. As for the bitcoin, Wuyts writes in his blog to sequencing software — and since it takes a
Wuyts says that the message contained in- that he plans on holding it until the right time. matter of days to read the data, it can protect
structions on how to claim the bitcoin, a few “I’m probably going to sell it [the bitcoin] investors against their tendency to sell in a
other notes, the logo of the European Bio- when the time is right and then use some of panic.
informatics Institute, and a sketch of James the money for my research. With the rest of
Vol. 02 NO 6
Crawly Caterpillar-like
Bot Navigates through the
Body Delivering Drugs
Quirks of caterpillars and jellyfish Inspire
“Millirobots” that walk, climb, jump and
swim through difficult terrain in order to de-
liver drugs to targeted areas.
We might as well one day be saying “Its
time take your bots!”
And I, for one, am looking forward with
great enthusiasm to this day. I’d rather swal-
low tiny bots as opposed to those hellish, icky
pills. Untethered small-scale (from several
millimetres down to a few micrometres in all
dimensions) robots that can non-invasively
access confined, enclosed spaces may ena-
ble applications in microfactories such as the
construction of tissue scaffolds by robotic as-
sembly, in bioengineering such as single-cell
manipulation and biosensing, and in health-
care such as targeted drug delivery and mini-
mally invasive surgery.
However, the existing small-scale robots
have very limited mobility because they are
unable to negotiate obstacles and changes in
texture or material in unstructured environ-
ments.
But now, a German research team has de-
veloped a robot that is about a seventh of
an inch long and looks at first like no more
than a tiny strip of something rubbery. Then
it starts moving. The robot walks, jumps,
crawls, rolls and swims. It even climbs out of
Panacea Biotec, Serum
Institute Ink Long-Term
Pacts
Panacea Biotec has now announced two
long term agreements with Serum Institute
of India (SII) and SII’s wholly owned sub-
sidiary, Bilthovan Biologicals B.Rajesh Jain,
Panacea’s Joint Managing Director, points
out that millions of children in developing
countries with an annual birth of about 121
million, will get easy access to the fully liq-
uid Hexavalent vaccine containing six impor-
tant antigens to protect against six diseases
– Diphtheria, Tetanus, Pertussis, Hepatitis B,
Haemophilus influenza type B and Polio.
Under the collaboration, Serum will be
manufacturing and distributing the fully liq-
uid Whole cell Pertussis (wP) and Salk-based
Injectable Polio Vaccine (IPV) based Hexa-
valent vaccine (DTwP-HepB-Hib-IPV) de-
veloped and commercialised by Panacea Bi-
otec, touted to be the first of its kind, a joint
release said.
In the next two years, both vaccine com-
panies will together get this wP-IPV-based
Hexavalent Vaccine introduced in the govern-
ment’s National Immunisation Programme.
“Serum Institute of India will ensure supply
of IPV bulk to Panacea Biotec, an important
constituent of the Hexavalent vaccine, from
its wholly owned subsidiary BBIO, a bioen-
gineering and pharmaceutical company, reg-
istered in The Netherlands having technology
and expertise for making the IPV, earlier pos-
sessed by only 3 other vaccine manufactur-
ers in the World,” the company press release
the pool, moving from a watery environment
into a dry one.
The robot prototype is small enough to
move around in a stomach or urinary system,
said Metin Sitti, head of the physical intelli-
gence department at the Max Planck Institute
for Intelligent Systems in Stuttgart, Germa-
ny, who led the research team.
“We looked at the physical mechanism of
locomotion of soft-bodied caterpillars and
jellyfish and The researchers from the Stutt-
gart-based Max Planck Institute for Intelli-
gent Systems found inspiration for the de-
velopment of the manoeuvrability talent in
nature: “When we build robots, we look at
the mechanics of the movement of soft-bodied
biological organisms, for example, and are
inspired by them“, says Metin Sitti.”With our
millirobot, the result is a mix of several soft
creatures such as beetle larvae and caterpil-
lars. However, a spermatozoid and a jellyfish
also served as models.”
The secret is magnetism. The millirobot,
which resembles a very small rectangle of
paper about four millimeters in length, is
made of an elastic polymer threaded through
with magnetic particles. Using existing mag-
netic-resonance technology, such as an ul-
said.
Adar C. Poonawalla, Serum Chief Execu-
tive and Executive Director, said the deal was
“historic” since two Indian vaccine compa-
nies were collaborating to address the unmet
needs of both the private and public market
globally. With the convenience of ‘Six in
one’, it has potential of over 250 million dos-
es in about four years, with a market size of
over $1.25 billion annually, he said.
February 6th, 2018.
trasound machine, doctors can control the
movement of the bot inside the human body.
The magnetic microparticles that are embed-
ded into the bot’s system allow the research-
ers to operate and control it using an external
magnetic field. By varying the strength and
direction of the magnetic field, they deform
the rubber strip in different ways. This allows
the millirobot to complete an obstacle course
similar to what would be encountered in the
human body: it can walk or roll across sur-
faces, jump across obstacles, crawl through
narrow tubes and swim on or in liquids. In
addition, it can grasp objects, transport them
and deposit them at defined locations.
That means the robot can potentially be
deployed anywhere that physicians need to
deliver a particular drug or other medical ma-
terial — in the digestive tract, say, or even
within the blood stream.
The team tested the bot in a synthetic surgi-
cal stomach model and in chicken meat tissue,
where the artificial multi-talent demonstrated By Disha Padmanabha
excellent results. When the researchers could
not observe it directly, they tracked where make these regions accessible non-invasively
and how exactly the robot made his way for- using our soft millirobot to perform diagno-
ward using ultrasound imaging. sis and therapy,” says Metin Sitti.
Great challenges still need to be overcome
before such a millirobot can be used in pa- “Our objective is that our millirobot will
tients: for example, it needs to prove that it one day transport medication to where it is
can be controlled within the human body. needed – similar to a parcel delivery to the
However, the researchers are confident that front door“, says Metin Sitti. “We aim to use
these hurdles can be taken. it in minimally invasive medical procedures
on the patient: either by swallowing the ro-
With the aid of such millirobots, a surgeon bot or by inserting it into the body through
would have direct access and precise control a small opening on the skin. From there, the
in areas of the body that can only be penetrat- robot can then move through the digestive
ed using a scalpel today. “Without surgery, tract or the bladder, or on to the heart – we
it is currently not possible to gain access to envisage numerous possibilities.“
many areas of the body. Our objective is to
By Disha Padmanabha
7
February 6th, 2018.
Researchers Reform Flu
Virus to Inhibit Pancreatic
Cancer
Metastatic pancreatic ductal adenocarcino-
mas (PDAC) are incurable due to the rapid
development of resistance to all current ther-
apeutics.
However, since oncolytic adenoviral mu-
tants have recently emerged as a promising
new strategy that negates such resistance, sci-
entists at the Queen Mary University in Lon-
don modified flu virus to block the growth of
pancreatic cancer.
“The new virus specifically infects and kills
pancreatic cancer cells, causing few side
effects in nearby healthy tissue,” said lead
author, Dr Stella Man, from Barts Cancer
Institute at Queen Mary University London
(QMUL), who described it as “selective and
effective”.
“If we manage to confirm these results in
human clinical trials, then this may become a
promising new treatment for pancreatic can-
cer patients, and could be combined with ex-
isting chemotherapy drugs to kill persevering
cancer cells.”
The research team took advantage of a
unique feature of pancreatic cancer cells – the
presence of a specific molecule called alpha
v beta 6 (αvβ6) on the surface. The research-
ers altered the flu virus in such as way that it
would feature an additional small protein on
its outer coat.
This extra protein recognizes the αvβ6-mol-
Gene on X Chromosome
Could be Reason Why
Lupus Disproportionately
Affects Women
9 of 10 individuals who develop lupus are
women. Also, XXY individuals have in-
creased incidence of lupus, suggesting that
X chromosome dosage could be an important
risk factor. Now researchers have found that
the gene, TLR7, escapes silencing in lupus
and may be a potent drug target for the dis-
ease.
Patients of systemic lupus erythematosus
(SLE), an autoimmune disease, produce anti-
bodies to their own body tissues rather foreign
proteins. The result is chronic inflammation
of a few or many body tissues, including the
heart, lungs, nervous system, skin, kidneys,
or joints. Viruses, some medications, ultra-
violet light, and specific genes are thought
to contribute to development of SLE. Lupus
also occurs more frequently in Japanese and
Chinese populations and in blacks.
The study carried out by researchers at the
French National Institute of Health and Med-
ical Research (INSERM), now demonstrates
that Toll-like receptor 7 (TLR7) that is en-
coded from the X chromosome escapes X in-
activation in B cells and myeloid cells in fe-
males and Klinefelter individuals (47,XXY).
Examination of blood cells led the research-
ers to find that the TLR7 was then expressed
8
Vol. 02 NO 6
ecules and attaches to it. Once bound, the
virus enters the cell and starts to multiply.
It produces copies of itself prior to bursting
out of the cell and thereby destroying it in the
process. The newly released viral copies can
then bind onto neighboring cancer cells and
repeat the same cycle, eventually removing
the tumor mass altogether.
The team used mice that had human pan-
creatic cells grafted onto them and a version
of the influenza virus that had been tweaked
to react to one of the unique markers of pan-
creatic cancer. The researchers say their new
technique has produced the most selective vi-
ral cancer therapy seen to date, which allows
it to be safely injected to spread around the
body.
Maggie Blanks, CEO of the Pancreatic
Cancer Research Fund, which partly funded
this research, said it was exciting to see the
work coming to fruition “with such positive
results”.
She said: “Developing more effective treat-
ments for pancreatic cancer becomes more
urgent every year as the incidence of the dis-
ease increases, and we hope to see this re-
search progressed further.”
The team are currently seeking funding to
move to clinical trials in humans in the next
two years. By Disha Padmanabha
on both X chromosomes—a state called TLR
biallelism—in many of the individuals’ im-
mune cells, which made them more likely to
“switch” the type of antibodies they produce.
The researchers think it’s this switch that
leads to a higher chance of the immune cells
making antibodies that attack the body’s own
tissues. A potential treatment would target
TLR7 to tamp down on immune activity
against normal tissues.
“Currently, there is no drug that can tar-
get TLR7 in the market or used in the clinics.
TLR7 is a known receptor for RNA nucleic
acid which normally comes from viruses, so
it is a sensor of RNA viruses, like HIV or flu
virus,” said Jean-Charles Guéry, research
director at the French National Institute of
Health and Medical Research (INSERM), in
an audio interview with Science Immunology.
“As such, there is some evidence that there’s
a sex bias in the susceptibility to flu virus or
HIV infection.” By Disha Padmanabha
Next up, the team plans to study TLR7 ex- “This may lead to new information regard- a predictive factor to predict the evolution of
pression in women with lupus and compare ing the level of biallelism of TLR7 in lupus disease, which is currently very difficult to
their findings against the data from healthy patients, and whether this could be used as do,” Guéry said.
women and men with Klinefelter syndrome.
Vol. 02 NO 6
Biogen’s MS drug
Potentiates Oncolytic
Viruses In Fight Against
Cancer
Oncolytic viruses are a promising anti-can-
cer platform, achieving significant pre-clin-
ical and clinical milestones in recent years.
They offer the attractive therapeutic combi-
nation of tumor-specific cell lysis together
with immune stimulation, therefore acting
as potential in situ tumor vaccines. Moreo-
ver, OVs can be engineered for optimization
of tumor selectivity and enhanced immune
stimulation and can be readily combined with
other agents.
However, these viruses need to reach tumor
cells and get inside them to achieve a thera-
peutic effect, and this does not always hap-
pen.Now, a bunch of scientists at the Ottawa
Hospital Research Institute in Canada have
identified a promising solution for this prob-
lem by combining oncolytic vesicular stoma-
titis virus (VSV) with dimethyl fumarate, a
small-molecule drug that is already in use for
some nonmalignant disorders and may also
have direct anticancer effects.
They have preliminary evidence that dime-
thyl fumarate (DMF), which is marketed by
Biogen as Tecfidera to treat multiple sclero-
sis, boosts the potency of oncolytic viruses.
In the course of their research, the team
tested the effect of a DMF-VSV combo on
several cancer cell lines, including renal car-
Sequenced Axolotl
Genome Unravels Genetic
Roots of Sophisticated
Regeneration
The replacement-parts king of the amphib-
ian world, the axolotl is a fascinating crea-
ture. With extreme regeneration capabilities,
these fellas are like the distant cousins of the
wolverine living in a tank (with a permanent
smile affixed).
Once revered by Aztecs, today the axolotl
appears in many forms. Native to Central
Mexico, these grinning amphibians are a
symbol for Mexican national identity. With
big branch-like gills, lizard-like limbs, and
cute perma-smile, it’s hard not to fall in love
with these little critters. But then it does not
just end there- in addition to being almost
criminally cute, these salamanders also pos-
sess remarkable regeneration capabilities.
It’s not unusual for amphibians to be able to
regenerate, but axolotls take it to the next lev-
el. On top of being able to regenerate limbs,
the animal can also rebuild their jaws, spines,
and even brains without any scarring- mak-
ing it a model of curiosity for regenerative
biologists.
Now, scientists in Vienna, Dresden, and
Heidelberg, have for the first time, complete-
ly mapped the genome of the Mexican axo-
lotl salamander. Despite its popularity as a
biological model and use for over 150 years,
February 6th, 2018.
cinoma, osteosarcoma and melanoma. When
they administered DMF to the renal carci-
noma cells four hours prior to giving them
VSV, they found the virus grew by more than
100-fold.
DMF also improved the performance of
herpesvirus, Sindbis and adenovirus, they
report.
Tecfidera’s anticancer properties have al-
ready been well documented, and the drug is
currently being tested to treat chronic lym-
phocytic leukemia and cutaneous T cell lym-
phoma.
The Ottawa team wanted to understand why
the MS drug enhances cancer-killing virus-
es, so they studied gene-expression patterns
on cancer cells infected with VSF, both with
and without DMF and related drugs. They
discovered that VSF ramps up the activity of
antiviral genes—but that DMF inhibits those
genes.
Strong evidence that Tecfidera is safe, cou-
pled with the availability of both marketed
and investigational oncolytic viruses, should
provide “a clear path toward clinical evalua-
tion of this promising combination therapy,”
the authors of the new study argued.
By Disha Padmanabha
this has been difficult due to the sheer size of
its genome at 32 billion base pairs.
The research was part of a long-term project
set out by the international group to develop a
molecular toolkit for the axolotl, identifying
important genes with a role in regeneration.
Using this, they would be able to identify the
cells that initiate regeneration and improve
our understanding of the molecular mecha-
nisms underlying it.
Researchers used the PacBio-platform, a By Disha Padmanabha
sequencing technology that produces long
reads to span large repetitive regions. A total “Taken together, these data point to a po- oshilow, co-first author of the study. “This is
of 72.435.954 reads were sequenced. Next, tential role in limb regeneration for several a turning point for the community of scien-
Gene Myers and Siegfried Schloissnig to- coding and non-coding sequences that have tists working with axolotl, a real milestone in
gether with colleagues developed software been lost or diverged rapidly in amniotes,” a research adventure that started more than
systems that can assemble the genome from senior author Eugene Myers, a researcher at 150 years ago.”
the 72 million pieces. the Max Planck Institute of Molecular Cell
On analysis of the genome, the researchers Biology and Genetics, and his colleagues Agreeably, we’re still a long way off of be-
found several genes unique to axolotls and wrote. “Future investigations of such se- ing able to fully regrow missing parts but se-
other amphibians that are expressed during quences are likely to be a fruitful avenue for quencing this huge genome- 10 times as large
regeneration. Interestingly, a gene called understanding the evolution of regeneration as the human genome- is a big step towards
PAX3, which was previously considered vi- capabilities.” decoding how this ability can evolve and
tal to the development of an organism, was function. In the nearer future, the study may
completely missing from the genome. In- “We now have the map in our hands to in- help us develop new ways to heal wounds
stead, the related gene PAX7 appears to have vestigate how complicated structures such faster to reduce recovery times and infection
taken over those critical functions. as legs can be re-grown”, says Sergej Now- risks.
9
February 6th, 2018.
Boosting Oestrogen
Activity Gives Hope of
New Neuroblastoma
Treatment Possibilities
Oncolytic viruses are a promising anti-can-
cer platform, achieving significant pre-clin-
ical and clinical milestones in recent years.
They offer the attractive therapeutic combi-
nation of tumor-specific cell lysis together
with immune stimulation, therefore acting
as potential in situ tumor vaccines. Moreo-
ver, OVs can be engineered for optimization
of tumor selectivity and enhanced immune
stimulation and can be readily combined with
other agents.
However, these viruses need to reach tumor
cells and get inside them to achieve a thera-
peutic effect, and this does not always hap-
pen.Now, a bunch of scientists at the Ottawa
Hospital Research Institute in Canada have
identified a promising solution for this prob-
lem by combining oncolytic vesicular stoma-
titis virus (VSV) with dimethyl fumarate, a
small-molecule drug that is already in use for
some nonmalignant disorders and may also
have direct anticancer effects.
They have preliminary evidence that dime-
thyl fumarate (DMF), which is marketed by
Biogen as Tecfidera to treat multiple sclero-
sis, boosts the potency of oncolytic viruses.
In the course of their research, the team
tested the effect of a DMF-VSV combo on
several cancer cell lines, including renal car-
Sanofi Outpaces Novo,
Buys Ablynx
for $4.8 billion
The French drugmaker has now acquired
Ablynx, for $4.8 billion after the Belgian bio-
tech turned down two previous bids by Novo
Nordisk.
The acquisition of Ablynx continues Sa-
nofi’s commitment to breakthrough inno-
vation, focused on technologies addressing
multiple disease targets with single mul-
ti-specific molecules.
Under the deal, Sanofi will pay 45 euros per
share in cash for Ablynx, a premium of 21
percent over its closing price on Friday, and
more than double the price before Novo went
public with its initial bid.
Nanobodies are a novel class of proprietary
next generation biologicals. Ablynx is at the
leading edge of Nanobody technology sup-
porting a deep pipeline of more than 45 pro-
prietary and partnered candidates for a wide
range of therapeutic areas such as hematol-
ogy, inflammation, immuno-oncology, and
respiratory diseases. Eight Nanobodies have
entered clinical development.
Ablynx would bring to Sanofi its first-in-
class acquired thrombotic thrombocytopenic
purpura (aTTP) candidate caplacizumab (an-
ti-von Willebrand factor [vWF] Nanobody),
a wholly owned development program. Ably-
nx has already filed for approvals for capla-
cizumab in the European Union, with plans
to do likewise in the U.S. during the first half
of this year.
10
Vol. 02 NO 6
cinoma, osteosarcoma and melanoma. When
they administered DMF to the renal carci-
noma cells four hours prior to giving them
VSV, they found the virus grew by more than
100-fold.
DMF also improved the performance of
herpesvirus, Sindbis and adenovirus, they
report.
Tecfidera’s anticancer properties have al-
ready been well documented, and the drug is
currently being tested to treat chronic lym-
phocytic leukemia and cutaneous T cell lym-
phoma.
The Ottawa team wanted to understand why
the MS drug enhances cancer-killing virus-
es, so they studied gene-expression patterns
on cancer cells infected with VSF, both with
and without DMF and related drugs. They
discovered that VSF ramps up the activity of
antiviral genes—but that DMF inhibits those
genes.
Strong evidence that Tecfidera is safe, cou-
pled with the availability of both marketed
and investigational oncolytic viruses, should
provide “a clear path toward clinical evalua-
tion of this promising combination therapy,”
the authors of the new study argued. By Disha Padmanabha
“With Ablynx, we continue to advance the
strategic transformation of our Research
and Development, expanding our late-stage
pipeline and strengthening our platform for
growth in rare blood disorders,” Olivier
Brandicourt, Sanofi’s chief executive officer,
commented. “This acquisition builds on a
successful existing partnership. We are also
pleased to reaffirm our commitment to Bel-
gium, where we have invested significantly
over the years in our state-of-the-art biolog-
ics manufacturing facility in Geel. We intend
to maintain and support the Ablynx science
center in Ghent.”
“Since our founding in 2001, our team has
been focused on unlocking the power of our
Nanobody technology for patients. The re-
sults of our work are validated by clinical
data,” said Ablynx CEO Edwin Moses, Ph.D.
“As we look ahead, we believe Sanofi’s glob-
al infrastructure, commitment to innovation,
and commercial capabilities will accelerate
our ability to deliver our pipeline. Our Board
of Directors feels strongly that this transac-
tion represents compelling value for share-
holders and maximizes the potential of our
pipeline to the benefit of all stakeholders.”
By Disha Padmanabha
Vol. 02 NO 6 February 6th, 2018.

Testosterone-induced
Molecule Could Explain
Why Men are Better
Guarded against MS
The cellular and molecular basis of sex-di-
morphic autoimmune diseases, such as the
CNS demyelinating disease multiple sclero-
sis (MS), remains unclear.
Women are much more likely to develop
autoimmune diseases, such as systemic lu-
pus erythematous, rheumatoid arthritis, and
multiple sclerosis. Sex hormones, including
estrogen and testosterone, clearly influence
disease susceptibility, but the precise cellular
and molecular targets of these hormones have
remained unexplained.
While most studies have focused on what
causes the damaging inflammation in fe-
males, there is also much to be learned by
studying the factors that confer protection to
males.
Now however, scientists at the Northwest-
ern University identified a testosterone-driv-
en pathway mediated by mast cell-dependent
IL-33 expression that limits the development
of a destructive immune response in males;
thereby specifying why men are better pro-
tected from this autoimmune disorder.
“This suggests a mechanism for the reduced
incidence of multiple sclerosis and other au-
toimmune diseases in males compared to
females,” said lead study author Melissa
Brown, PhD, professor of Microbiology-Im-
munology. “These findings could lead to an
entirely new kind of therapy for MS, which
we greatly need.”
In MS, immune cells attack the myelin
sheath, a membrane that wraps around the
nerve axons within the brain and spinal cord.
The sheath acts as insulation and assists in
sending nerve signals from the brain and spi-
nal cord to the rest of the body. The damage
to the myelin sheath interrupts normal nerve
signal conduction and can result in a variety
of symptoms including sensory disturbances,
loss of motor function and cognitive deficits.
In the new Northwestern study the research-
ers found that, in male mice, testosterone was
resulting in the production of a molecule
called cytokine IL-33, which was seen to
trigger a pathway that prevented the produc-
tion of Th17. When the researchers treated
female mice with IL-33 the damaging effect
of Th17 on the myelin sheath was effectively
reversed.
“Because testosterone levels are seven-to-
eight times lower in adult women compared
to men, we speculate there are insufficient
levels in females to activate this protective
pathway,” says Brown, lead author on the
study. “But we showed we can activate the
pathway with the guardian molecule, IL-33.”
The researchers also found that women tend
to develop MS at a younger age and have a
relapsing-remitting course of the disease. On
the other hand, men tend to develop the dis-
ease later in life and it usually worsens with-
out a period of improvement. The timing of
the disease development in men also corre-
lates with age-related reduction of testoster-
one levels.
The hope Northwestern researchers now
have is that discovering this new specific
pathway will allow more targeted therapies
By Disha Padmanabha
to be developed. It’s also suggested that this
testosterone-driven protective pathway could
be a culprit in other autoimmune diseases
that are seen more prominently in women
over men.
“Our findings have identified new and
more specific cellular and molecular tar-
gets for immune intervention that we hope
will lead to better therapies that leave most
of the immune system intact,” Brown said.
“This testosterone-driven protective pathway
should also be studied in other female-biased
autoimmune diseases.”

NIH Rolls Out Large-Scale

Study to Evaluate HIV
Treatment in Pregnant
Women
Perinatal HIV transmission refers to HIV
transmission from mother to child during
pregnancy, labor and delivery, or breastfeed-
ing. It accounts for the majority of childhood
HIV infections. Each year worldwide, an es-
timated 1.5 million women living with HIV
give birth.
Previous NIH researches have helped pave
the way for development of strategies to pre-
vent perinatal transmission both in high-re-
source countries like the United States and in
resource-limited settings around the world.
Now, the NIH has launched a large interna-
tional study to compare the safety and effica-
cy of three antiretroviral treatment regimens
for pregnant women living with HIV and the
safety of these regimens for their infants.
In the new study, investigators will compare
the virologic efficacy of the three regimens
by measuring the mother’s viral load (amount
of HIV in the blood) at delivery. The study
also will compare how the regimens affect
rates of adverse pregnancy outcomes.
“Women should have access to the best
available HIV medications throughout their
lives,” said Anthony S. Fauci, M.D., director
of NIH’s National Institute of Allergy and In-
fectious Diseases (NIAID). “Our priority is
to evaluate newer, improved antiretroviral
drugs during pregnancy to identify the opti-
mal regimens for women living with HIV and
their infants.”
The study will focus on the current pre-
ferred first-line regimen for pregnant women
recommended by the World Health Organi-
zation (WHO) and two regimens containing
newer antiretroviral drugs that are becoming
By Disha Padmanabha
more widely used. It will provide data on the
use of these newer drugs during pregnancy,
prophylaxis following birth. tings with high HIV prevalence. We hope that
helping to ensure that women living with
The researchers will monitor both the wom- the [the trial] will provide urgently needed
HIV and their infants receive the best availa-
en and their infants for 50 weeks after deliv- information regarding the safety and efficacy
ble treatments.
ery, and study staff will provide the women of these newer drugs in pregnant women and
The study, known as IMPAACT 2010, is
with counseling on antiretroviral medication their babies, so that optimal antiretroviral
a phase 3 study and will enroll 639 women
adherence. Researchers will also closely regimens can be offered to pregnant women
who are 14 to 18 weeks pregnant, are living
monitor the women’s viral loads and test the and recommended for first-line treatment of
with HIV, and are not currently taking an-
infants for HIV. If an infant becomes infected adults living with HIV throughout the world.”
tiretroviral treatment.
during the study, investigators will provide
Clinical trial sites in the United States and
referrals to local sources of HIV care and “Therapies for pregnant women and new
Zimbabwe are now open for enrollment, with
treatment. mothers should be based on the best available
additional sites in Botswana, Brazil, Haiti,
evidence, always keeping in mind the health
India, Malawi, South Africa, Tanzania, Thai-
Co-chair of the study Dr Shahin Lockman of the woman, her developing fetus and her
land, Uganda, the United States and Zimba-
said: “Limited pregnancy data for newer, newborn,” said Nahida Chakhtoura, M.D.,
bwe expected to open in the coming months.
better antiretroviral drugs—such as DTG of the Maternal and Pediatric Infectious Dis-
The women will be randomly assigned to
and TAF—can mean that pregnant women ease Branch at NICHD. “The results of this
be administered EFV/FTC/TDF, DTG/FTC/
may not receive the most effective and safest study will help inform optimal treatment of
TAF, or DTG/FTC/TDF. Their infants will
medications, and can delay the general adop- pregnant women living with HIV in both re-
also be enrolled in the study and will receive
tion of better regimens in low-resource set- source-limited and well-resourced settings.”
local standard-of-care interventions for HIV

11
February 6th, 2018.
Study Uses HiPSCs to
Demonstrate Contribution
of Molecular Switches in
Disease Risk
Scientists at the Wellcome Sanger Institute
and their collaborators, have now uncov-
ered the contribution of molecular switches
of genes in disease risk. The study demon-
strates, for the first time, how immune cells
created from human induced pluripotent stem
cells (HiPSCs) can model immune response
variation between people.
“We have found that the impact of genetic
variants on how people’s immune cells re-
spond to a pathogen like Salmonella are con-
dition-specific – they are only visible at cer-
tain stages of infection. This means that the
effects of genetic differences in immune dis-
orders could be missed in research, if scien-
tists aren’t studying both the genes and their
control regions, the regulatory elements, of
immune cells at all stages of an infection,”
said Dr Daniel Gaffney, Group Leader and
senior author from the Wellcome Sanger In-
stitute.
“A benefit of using stem cells rather than
pre-existing blood cells is they’re very flex-
ible, and enabled us to study the effects of
stimulation at two different levels. We an-
alysed which genes in the genome were ex-
pressed during each stage of infection, but
also looked at the activity of enhancers – the
www.biotecnika.org
12
Vol. 02 NO 6
molecular ‘switches’ that controlled the ex-
pression of those genes. This novel combi-
nation of tools enabled us to see otherwise
hidden effects of genetic variation on immune
response” said Dr Kaur Alasoo, previously
from the Wellcome Sanger Institute and now
based at the University of Tartu, Estonia.
In the course of the investigation, the team
By Disha Padmanabha
differentiated human iPSCs into macrophages
that were then studied in four different states:
unstimulated, after 18 hours of stimulation
with a signaling molecule interferon-gamma,
after five hours infection with Salmonella,
and after interferon-gamma stimulation fol-
lowed by Salmonella infection.
They discovered that genetic variation im-
pacts on the readiness of the immune cells to
tackle an infection. They found that in par-
ticular, some individuals’ immune cells were
ready to deal with the Salmonella infection,
whereas other individuals’ macrophages
were less ready and took longer to respond.
This level of ‘readiness’ was due to a phe-
nomenon known as enhancer priming, where Macrophages before (left) and after (right) stimulation. Credit: Kaur Alasoo, University
some of the switches were already turned on of Tartu
in the unstimulated cells to facilitate a quick- mune disorders. mune activation, and highlights the relevance
er response. In some cases, the immune cells The researchers said their results “illustrate of these hidden genetic effects for decipher-
could be overly eager and this can lead to an how pre-existing genetic effects on chroma- ing the molecular architecture of disease-as-
inflammatory response associated with im- tin propagate to gene expression during im- sociated variants.”