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UNLOCKING
GRIDLOCK
Clearing the road
for driverless cars
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EDITORIAL
3 Notes from the editors
F E AT U R E S &
I N N O VAT I O N S
4 Hay fever
8 Green lights all the way
RESEARCH
HIGHLIGHTS
13 A better angle
4 F E AT U R E S &
I N N O VAT I O N S
on microscopic devices
14 Taking a stab at microbes
15 Shedding ‘light’
on antibody design
16 A new weapon against
the Zika virus
17 Computing the ebb and flow
18 Using a mouse to make an ‘iMac’
19 Of mice and men
20 Gut bacteria implicated
in liver inflammation
17 18 21 A catalyst for change
in chemical etching
22 Keeping stem cells naïve
24 Bridging the security divide
for chat applications
25 What a hungry fly can tell us
about obesity
26 A smoother finish
allows fluids to flow
27 Hepatitis B exploits
RESEARCH
HIGHLIGHTS
29 Classify and conquer
30 Frequency fingerprints increase
crime-fighting power
32 Diverting distraction
33 Getting to the root of hair loss
34 A simpler path
35 Fetal immune system
developed, but tolerant
36 Mapping RNA editing
37 Escaping silicon
38 More evidence for metformin
40 Hormone discovery opens path
for new pre-eclampsia treatment
41 Let liquid fingers point the way
42 All in a molecule of water
for effective cancer therapy
NEXT ISSUE
35 46 52 A sneak peek of Issue 11
2 A*STAR RESEARCH Issue 10 | January – March 2018
CONTENTS | F E AT U R E S | RESEARCH HIGHLIGHTS | NEXT ISSUE
NOTES
FROM THE EDITORS
Editorial board member, Arseniy Kuznetsov,
introduces the latest issue of A*STAR Research
W
elcome to the second called metasurfaces, that could eventu- discoveries that have important implica-
edition of A*STAR ally replace bulky glass lenses, enabling tions for fetal and maternal health: the
Research for 2018, where higher imaging resolution and providing discovery of a hormone that could treat
we showcase some of the an excellent compact and lightweight a dangerous complication of pregnan-
latest innovations and research from solution for mobile device cameras cy (page 40), and the unravelling of
A*STAR. and head-mounted displays (page 49). mysteries surrounding the fetal immune
More than half of the world’s Another example is a new ultra-high res- system (page 35).
population lives in urban areas — a olution printing method based on reso- We also have a full-length feature
proportion that is expected to grow to nant silicon nanostructures, which can that examines a health issue that affects
two-thirds by 2050. With overcrowding now achieve a spread of colours beyond many of us — allergies, and a common
comes traffic jams and gridlocks, but standard RGB (page 51). Additionally, culprit that lurks in our homes (page 4).
smarter transport systems that are being a team of A*STAR and NUS researchers Another inflammation-related article
developed and tested in Singapore could have developed transducers that could reveals a surprising role for gut bacteria
overcome these problems (read more in transfer data directly from electrical in chronic viral hepatitis, which may
our cover story on page 8). signals to plasmonic circuits and back, influence future treatments (page 20).
Several exciting inventions have also avoiding speed reductions from elec- As usual, there are many more
emerged from the field of nanophotonics tro-optical components (page 43). interesting stories in the rest of the
and plasmonics. These include arrays Major advances have been made magazine, and I hope you will enjoy
of resonant dielectric nanostructures, in medicine as well — including two reading them.
UNLOCKING
GRIDLOCK
Clearing the road
for driverless cars
© Colin Anderson/Photographer’s Choice RF/Getty
COVER IMAGE
Singapore is an ideal test
bed for intelligent traffic
innovation. [page 8]
© RETOKA
HAY
With dust mites likely causing
allergic rhinitis symptoms in
an enormous 40 per cent of
Singapore’s population, research in
the city state is yielding some very
interesting insights into the role of
FEVER
climate, genetics and childhood
F
irst, the bad news: on busy cities in tropical
There’s no simple cure climates — environments in
for allergies… which dust mites thrive.
at least for now. In fact, allergic rhinitis
One of the most could be having a hefty effect
widespread, allergic rhinitis on productivity worldwide.
(or hay fever) affects as much Roughly eight per cent of adults
as five per cent of the world’s experience allergic rhinitis in
population. The hallmarks the United States, while other
are sniffling, itching and national surveys have estimated
sneezing, and it strikes prevalence rates of about
indiscriminately, regardless of six per cent in France and 29
age or ethnic background. per cent in the United Kingdom.
No-one knows why some More than just an irritation,
people develop this common common symptoms of
allergy and not others, but allergic rhinitis are also loss
An A*STAR study has suggested that wheezing and eczema in infancy are correlated
scientists in Singapore have of sleep, irritability and with having an increased risk of sensitization to airborne allergens, including allergic
recently found some interesting fatigue — all of which have rhinitis (hay fever), later in childhood.
clues in cell responses and an effect on performance at
childhood experiences. work and school.
Allergies are essentially
glitches of the immune system. EIGHT-LEGGED CULPRIT
The human body responds to
some usually harmless material
A survey of 8,000 adults in
Singapore published in Allergy
75% 40%
of Singaporeans
of Singaporeans
have allergen
by activating an immune in 2014 found an astonishing antibodies
show allergy
symptoms
response that releases a number 40 per cent of those surveyed
of substances. The main culprit, reported symptoms of
histamine, sparks inflammation allergic rhinitis.
and is responsible for the most In fact, by testing the blood
irritating symptoms, including of nearly 600 people, the team tropicalis. The unpleasant truth with other colleagues at
itching and swelling. found a staggering 80 per cent is that people are not allergic to SIgN and collaborators at
In spring, people often suffer of Singaporeans had antibodies, the mites themselves, but their the National University of
© Getty Images/Clover No.7 Photography
from what is known as seasonal called Immunoglobulin E (IgE), fecal matter. Singapore (NUS).
or intermittent allergic rhinitis that are specific to house “To verify our findings, “Astonishingly, we found
— triggered by pollen from trees dust mites. we looked at a much larger the figure was similarly high:
and grasses, as well as fungal Two species of dust sample size of more than 75 per cent of this larger
spores. Less seasonal is the mite that are often found in 7,000 volunteers,” says Anand group had antibodies against
allergic rhinitis triggered by dust mattresses, bed linen, carpets Andiappan, a senior research house dust mites.” That
mites, animal dander (such as and upholstered furniture were scientist at A*STAR’s Singapore means that three-quarters of
pet fur), mold and cockroaches. implicated: Dermatophagoides Immunology Network (SIgN), Singaporeans potentially have
The latter can be a huge burden pteronyssinus and Blomia who worked on the study a dust mite allergy.
IT’S NOT ABOUT ETHNICITY This suggested that climate is a summer, they usually die off could be involved, such as pollen,
As part of the 2014 study, the significant factor in determining during the drier winter months. fungi and animal dander. “The
researchers looked closely at exposure levels and allergic To Olaf Rötzschke, a advantage here in Singapore
the ethnic Chinese portion of response: People from countries principal investigator at SIgN is that we have a perfect
respondents and found that in the tropical belt with similar who is now leading the most environment for analysis because
climate, rather than genetics, climates — Singapore, Malaysia, comprehensive adult allergy the problem-causing allergen
appears to have the most impact Indonesia and others — show cohort study conducted in [dust mites] is so specific.”
on sensitization. Andiappan similar reactivity to dust mites, Singapore, these findings were “We started out with a big
notes: “People who had just suggesting they had been nothing short of “spectacular”. exploratory study — we weren’t
arrived in Singapore from exposed before. People from He began to look more closely at even focusing on allergies at
mainland China seemed to temperate climates, such as the problem. the beginning,” says Rötzschke.
have a much lower prevalence mainland China and Hong Usually, Rötzschke says, “We effectively cast a net, and
of the house dust mite allergy Kong, generally become more allergy studies are complicated this fishing approach enabled
and allergic rhinitis symptoms sensitive to house dust mites by the sheer number us to build a huge database,
compared to those who had the longer they stay of factors so we could really dive into
stayed more than eight years.” in Singapore. that exploring immune responses
In some cases, he says, the Dust mites and genomics.”
difference was evident after thrive in the hot and Rötzschke points out that
just three years of living humid conditions urbanization and lifestyle
in Singapore. that are the norm changes — namely, spending
By contrast, there was in tropical zones. In more time in indoors — may
no significant difference in temperate climates, be the most significant factors
reactivity to dust mites between although they can behind an overall increase
Chinese people from Malaysia be a problem in the prevalence
and those born in Singapore. in the of airborne
GREEN LIGHTS
ALL THE WAY
W
e could ble. Because of this coordinated
increase effort, Singapore — one of the
traffic densest cities in the world — sits
efficiency by at a comfortable number 55 in
up to 45 per TomTom’s congestion world
cent,” Yang Bo says, discussing ranking, well behind less pop-
a futuristic intersection without ulous cities such as Sydney, San
traffic lights he modeled at Francisco and Auckland.
A*STAR’s Institute of High
Performance Computing ELIMINATING TRAFFIC
(IHPC) last year. Creating LIGHTS FROM
smoother traffic flows could INTERSECTIONS
also save millions of liters of Yang proposed his lightless
fuel that would otherwise be intersection in 2017, along
consumed globally by vehicles with a colleague, Christopher
idling at traffic lights each Monterola. Cars would
day. Indeed, a lot of fuel and continuously move through
commuter time could be saved these junctions, and while
by implementing the many ideas human drivers still steer,
being modeled at the IHPC, acceleration, deceleration and
including several to improve interactions with other cars
the ‘hive brains’ guiding the are controlled by a beacon
movements of taxis and ride- installed on the dash and at the
sharing vehicles. intersection. He says
The IHPC is fortunate, as efficiency gains are found in
Singapore is a major test bed reducing redundant waiting
for intelligent transport systems. for light changes and human
Its roads pulse with information factors such as “phantom
and subtle adjustments: smart traffic”, in which drivers slow
intersections vary their cycles unnecessarily at the fringes of a
according to the flow of traffic congestion, with rippled effects
and intelligent ramp meters slowing cars upstream.
note the density of cars, while It’s a response to a hope-
a congestion tax, politically ful, but uncertain future as
contentious in other cities, is autonomous vehicles begin to
collected by electronic gantries penetrate the market, Yang says.
daily. This is all managed by the “The question is: How do we
city’s Land Transport Authority make a new system that has the
(LTA) — who has 164 kilometers least-required modification to
of expressways and road tunnel vehicles until we fully imple-
systems wired for data collec- ment driverless cars?” While
tion and video surveillance. The tech behemoths such as Didi
© Malorny/Getty
LIGHTLESS
INTERSECTIONS
An intersection
proposed by Bo Yang
and Christopher
Monterola at the
Institute of High
Performance
Computing could see
cars flow through
continuously without
having to stop.
A cruise control-like
device installed in car.
A beacon or intersection
control device.
the aim of his model is to make driverless will still be on the its simplest, Yang’s intersection highly localized, this system
something practical today and roads,” he points out. only require that vehicles to be at is also easy to implement and
for the anticipated “long transi- In 2016, the world’s first driv- Level 1 — the intelligent car bea- requires minimal energy to run.
tion period” to fully driverless erless car policy emerged from con could take over some aspects Yang adds that his modeling of
technology. “If you have a high the United States and outlined only in the intersection ‘zone’ the intersection sees overall
technological barrier, say you five levels of autonomous vehicle and would protect passengers efficiently gains even if today’s
© shanghaiface/Getty
have a system that needs an ranging from regular cars with using an algorithm that was cars (he calls them ‘legacy
autonomous vehicle, it’s going driver assistance (Level 1) to designed to create a mathemati- cars’) make up 70 per cent of
to take a long time to imple- fully automated machines with cal repulsion between vehicles. the traffic. He explains that
ment, because cars that aren’t no steering wheel (Level 5). At Because the zone would be for today’s vehicles, these
account for vehicle-pedestrian Computing and Engineering vehicles will often pass a num-
interaction, Yang’s intersec- Corporate Lab in a collaboration ber of potential passengers to get
tion is still theoretical. But in between A*STAR, technology to a booked passenger.
Singapore, ideas like this can be- giant Fujitsu Limited (Fujitsu) The IHPC collaboration
come reality; the city’s advanced and the Singapore Management soon spawned an app using
thinking on the road means University (SMU). Zheng’s team FALCON.Amy, called the Driver
it has bucked dominant world used the taxi data to train a Guidance System (DGS). Within
trends and actually improved its learning neural network they the year, the app was already
congestion levels in recent years. devised — called Fusion directing taxis to roads where
The red carpet is also being Architecture for Learning and they’re likely to find a fare, and
laid out for companies diving Cognition with Alternative being used in the National Taxi
into the autonomous vehicles MemorY (FALCON.Amy) — Association (NTA) SkillsFuture
market by the Singapore Auton- to predict pick-up hotspots for Training Programme.
omous Vehicle Initiative (SAVI), taxi drivers. Zheng says Singapore’s
a joint partnership between the taxi association is big supporter
LTA and A*STAR. They see Sin- of the project. “They are very
gapore as the logical home for anxious to improve technology
the world’s driverless statutory TIMES CHANGE FOR TAXIS for their drivers,” he says. While
Singapore’s average daily taxi ridership
and technical firsts. At the mo- fell to 785,000 last year, an 18-per
reducing empty taxi roaming
ment, there are only a handful cent drop from 2016 according to data alleviates congestion by decreas-
of official city-based driverless from Land Transit Authority. ing unnecessary road use, it
trials in the world; this year AVERAGE DAILY TAXI RIDERSHIP
could also boost profitability
Singapore will host both the for taxis struggling in an
2016 954,000
world’s first driverless taxi trials era when disruptive technol-
for the MIT spin-off nuTonomy 2017 785,000 ogies are cutting into their
and commercial driverless car bottom line.
tests for electronics and software The DGS was primed to pre-
company, Delphi Technology. However, the results of a survey dict fare locations using roughly
published by the Public Transport
Council in February show satisfaction
two years’ worth of taxi data.
OPTIMIZING TAXI ROAMING with taxi services has improved Numbers from a free trial for taxi
This forward-thinking approach despite lower ridership. The number of drivers showed significant im-
commuters satisfied with taxi services
to its roads is typical. For rose 4 per cent between 2016 and
provements for cab drivers during
decades now, Singapore’s 2017, and the mean satisfaction score off-peak hours; those using the
government has been increased by 0.4 points. app decreased their average emp-
extraordinarily clever with its MORE COMMUTERS SATISFIED
ty roaming time between fares in
road data. For example, each the city between midnight and
of the city’s more than 20,000 2016 94.4%
6am from 17 to 12 minutes.
taxis are required to transmit 2017 98.5% Early feedback, collected
its GPS location and working through discussions with driv-
status every 30 seconds to the COMMUTER SATISFACTION SCORE
ers who participated in the trial,
LTA, so that it can monitor a was also predominantly positive,
key mode of transport in a city 2016 7.5 / 10
particularly for new taxi drivers
where fewer than one in 10 own 2017 7.9 / 10 who don’t already know where
a private car. Some of this data to find fares. However, some taxi
intersections mean using a is also being harnessed by the drivers reported a reluctance to
system similar to when a IHPC to come up with ways to miss out on booking fees.
driver stops and waits for the improve taxi occupancy. At peak demand, these street This doesn’t bother Zheng.
right moment to cross when In 2016, a team led by Qin pickups become much more While, it seems that companies,
he or she sees a stop sign. The Zheng, a senior scientist also at efficient than bookings systems, such as Uber and Grab are here
caveat is “it will be a little slower the IHPC, started by looking at which include disruptors such to stay for the mid-term, he says
Source: data.gov.sg
for older cars, but that will a week’s worth of taxi data. To as Uber and Asian counter- the long-term thinking is that
encourage people to upgrade.” examine the 3.6 million-odd parts, Grab and Didi. IHPC and they will be used for another five
Without real-world data points, they worked other studies have shown that in to ten years, after which the city
implementation and data to with the Fujitsu-SMU Urban high-demand conditions, will move to driverless taxis.
were to be adopted by 50 per points out that “the tricky thing the road will also reduce traffic Driverless cars are perhaps still
cent of taxis — in a system in about Singapore it is that it’s a and travel times, says Yang. a decade away, but Singapore
which more than one person is relatively rich society, so people But those benefits will only and its researchers are position-
an individual paying passen- don’t really want to give up their become evident if advanced ing themselves as front runners
ger — the 15,000 taxis on the privacy to save a few dollars.” modeling like the IHPC’s “can in the road race towards the
road at any one time could be But Yang’s work shows that convince policy-makers to smartest cities of the future.
reduced to 6,000. ride-sharing taxis may find a cultivate a culture of ride
But he’s quick to explain foothold during peak hours sharing”, he says. “Our results For references, visit the online
version of this article at:
that this number needs to be and bad weather, when passen- show that a good algorithm https://www.research.a-star.edu.sg/
taken with a grain of salt: “We’re gers are faced with surges in for taxi ride-sharing can really feature-and-innovation/7831
MANUFACTURING
SiO2 2.0μm
Making increasingly small mass production of smaller and at scales of five microns or during the etching process —
microelectromechanical systems more reliable devices for a range less, are not dependable. The accelerated corner sputtering
(MEMS) has proved very chal- of new applications. etching method, with sidewall and sidewall polymerization,”
lenging, limiting their anticipat- polymerization, is not suitable explains Bliznetsov.
ed potential. Now, researchers at Combining these as the width at the bottom of Combining these processes
A*STAR have developed a versa- processes into a the vias shrink considerably. into a two-step method achieves
tile and cost-effective technique two-step method Another method, involving the greater control over the etching
for making devices with much achieves greater transfer of a photoresist profile process and produces micron-
greater precision and reliability control over the into an etched layer, limits the sized vias with smooth, tapered
for use in biotechnology and maximal depth of vias due to walls. And by minimizing the
etching process
medical applications.1 excessive loss of the photoresist sidewall angle of the vias, it is
MEMS are used in
and produces mask resulting in unacceptably possible to fabricate devices
applications ranging from airbag
micron-sized vias rough sidewalls. that can be better protected
systems and display screens to with smooth, To overcome these restric- and have more reliable metal
inkjet cartridges. They are tiny tapered walls. tions, the researchers developed contacts, greatly improving their
devices that combine mechanical a two-step plasma etching performance.
and electrical components. “MEMS are following the process. This combines firstly “Precise control of
Current manufacturing general trend of miniaturization photoresist tapering, which sidewall angle has use in many
© 2017 IEEE. Reprinted, with permission, from Ref 1.
technologies, however, are in electronics, with devices that modifies the photoresist from applications, and we are now
expensive and lack the precision are reducing in size from the a vertical to a tapered profile, planning to fabricate functional
for making devices with micron tens of microns to one micron and then an oxide etching with magnetic memory cells, which
and sub-micron scale features. or less,” says Bliznetsov. “But the sidewall polymerization with require pillars of magnetic
This led Vladimir Bliznetsov techniques used to manufacture better selectivity to photoresist. material with sidewalls having a
and colleagues from the A*STAR top metal contacts to devices This produces vias with minimal specific angle,” says Bliznetsov.
Institute of Microelectronics to with such microscopic dimen- dimensions down to 1.5 microns,
1. Bliznetsov, V., Li, B., Lee, J. W., & Lin,
develop a versatile and low-cost sions are costly and unreliable.” and smooth sidewalls with an-
H. MEMS industry-worth etching to
method for fabricating MEMS Current methods for creating gles of around 70 degrees. fabricate tapered structures in SiO2 .
at dimensions not previously channels, called vias, with “We combined two effects Journal of Microelectromechanical
Systems 26, 1400–1407 (2017).
possible, edging closer to the tapered sidewalls in MEMS which are usually harmful
addition to being clean and safe, life,” says Zhang. His team is
this technology does not require currently working on developing
externally applied chemicals,” nano-dagger surface prototypes
says Zhang. and other antimicrobial
The researchers added a nanopatterned surfaces using
zinc-based solution to various different materials.
surfaces, including rubber,
glass, wood, and metal foil, 1. Yuan, Y. & Zhang, Y. Enhanced
biomimic bactericidal surfaces by
then immersed the surfaces in
coating with positively-charged ZIF
an aqueous solution containing
nano-dagger arrays. Nanomedicine:
amine-rich 2-methylimidazole Nanotechnology, Biology, and
A*STAR researchers have developed positively charged nano-dagger arrays to form a so-called zeolitic Medicine 13, 2199–2207 (2017).
(pictured) that effectively kill microbes, such as E. coli and Staphylococcus aureus. imidazolate framework coating.
THERAPEUTICS
SHEDDING ‘LIGHT’
ON ANTIBODY
DESIGN
The light chain
subunits of therapeutic
antibodies impact drug The light chains of Y-shaped antibody
molecules (shown here in blue) impact
performance and yield drug performance and yield.
Antibody-based drugs target molecules and that the from a recombinant cell culture its framework regions can
have long been a mainstay of ‘framework’ regions of light system, although it did not impact key factors of a good
treatment for many conditions, chains provide structural severely affect the ability of therapeutic antibody, even at
especially cancer and support to allow target contact. trastuzumab to bind its target, a sites that are not known to be
autoimmune diseases, but there protein called human epidermal directly involved in binding or
may still be room for improving growth factor receptor 2 (Her2). purification,” he says.
‘‘The light chain
these complex biological Delete both amino acids, Although these initial
therapies. An A*STAR study has
and its framework however, and both antibody findings demonstrate only
found that changes to a part of
regions can impact production and Her2 binding the negative consequences
antibodies that’s often overlooked key factors of a decreased significantly. of altering an antibody’s
by protein engineers and drug good therapeutic Structural modeling light chain, Gan and his team,
companies can have dramatic antibody.’’ and experiments conducted in work not yet published, have
effects on target binding and by members of Gan’s also found ways to enhance
manufacturing yield. To evaluate the importance Antibody Product and both production and target
An antibody is made up of the light chain in antibody Development lab, including binding through other light
of four polypeptide chains: performance, a team led by co-first authors Chinh chain modifications. “This
© PIXOLOGICSTUDIO/SCIENCE PHOTO LIBRARY/Getty
two ‘heavy’ chains form the Samuel Ken-En Gan from Tran-To Su and Wei-Li Ling, is only the first in a series of
Y shape of the molecule, and the A*STAR Bioinformatics revealed that the deletions papers from my lab to show
two ‘light’ chains sit alongside Institute and the p53 impaired the interaction that we need to consider the
them. To date, most of the Laboratory deleted two amino between trastuzumab and antibody as a whole and not
modification techniques in acids in the framework region of a protein used for antibody just as a sum of different
therapeutic antibody design the light chain of trastuzumab, purification. That explains the parts,” Gan says.
have focused on the heavy an antibody drug for treating yield reduction, while decreased
1. Su, C. T., Ling, W. L., Lua, W. H.,
chains. The light chains were breast cancer, sold under affinity for Her2 explains why
Poh, J. J. & Gan, S. K. The role of
generally considered less the brand name Herceptin. the deletions also obstruct Antibody Vκ Framework 3 region
important, even though it Either deletion on its own, antibody performance. towards Antigen binding:
Effects on recombinant production
has been demonstrated that the researchers found, led to a “This study shows and Protein L binding.
they’re also involved in binding reduction in antibody secretion that the light chain and Scientific Reports 7, 3766 (2017).
An immune cell
involved in brain
IMMUNOLOGY defense, called a
microglia, made
from a stem cell–
derived macrophage.
USING A MOUSE
TO MAKE AN ‘IMAC’
A new method for making
specialized immune cells from stem
cells offers a tool for modeling
inflammatory diseases in the lab
A specific type of white blood These iMacs were genetically into a type of immune cells, characterized by macrophage
cell, considered the sentinel of and functionally similar to known as microglia, involved in dysregulation in different organ
the immune system, can now be early macrophages found in brain defense. systems. For example, the iMicros
made in almost limitless volumes the developing embryo. And could help scientists shed light
in the laboratory. by making iMacs from the These cells provide on the immune contributions
A two-step protocol, iPSCs of someone with Familial a tractable systen to neurodevelopmental
developed by A*STAR researchers, Mediterranean Fever, a rare for studying the disorders such as autism and
for turning reprogrammed stem inherited autoimmune disease, ways in which a neurodegenerative disorders such
cells into various types of tissue- they showed that these cells as Alzheimer’s disease.
genetic disease
specific white blood cells, known provide a tractable system for “[These cells] will provide
as macrophages, could help studying the ways in which
can cause immune insights into the mechanism
scientists design new medicines a genetic disease can cause
signalling to go of primitive macrophage
for inflammatory diseases of the immune signaling to go awry. awry. maturation into microglia,”
lungs, brain and other organs. Ginhoux’s team next coaxed says Ginhoux. “Furthermore,
The first step in the the iMacs to form the kinds of The researchers could also the co-culture model has the
process involves converting mature macrophages found in form these lab-made microglia potential to serve as an in vitro
© 2018 A*STAR Singapore Immunology Network
induced pluripotent stem different tissues of the adult — or iMicro cells, as they called drug screening system for the
cells into a kind of primordial body. In one experiment, the them — by implanting iMacs development of novel therapies
macrophage. Florent Ginhoux researchers mixed the iMacs in directly into the brains of against brain diseases.”
and his colleagues at the a lab dish with neurons that had newborn mice. Putting iMacs into
A*STAR Singapore Immunology also been made from the same the lungs of mice also resulted in 1. Takata, K., Kozaki, T., Lee, C. Z. W.,
Thion, M. S., Otsuka, M. et al. Induced-
Network devised a recipe for batch of iPSCs. After about a lung-specific macrophages. pluripotent-stem-cell-derived primi-
doing this with either mouse or week of co-culturing, the iMacs With the protocols all worked tive macrophages provide a platform
human cells, creating what they started to develop tentacle-like out, these kinds of tissue-resident for modeling tissue-resident mac-
called iPSC-derived primitive projections called dendrites, immune cells now provide a rophage differentiation and function.
Immunity 47, 183–198.e6 (2017).
macrophages — or simply iMacs. suggesting they had morphed valuable tool for studying diseases
GENETIC
DISEASE
OF MICE
AND MEN
A rare mutation
causes severe growth
A*STAR
retardation and spine researchers
malformation in have uncovered
a genetic mutation
humans and mice that causes severe growth
retardation in humans and mice.
Mutations in a gene associated growth retardation and some mice. A significant number of developed longer cilia than the
with cellular proliferation skeletal defects that resemble these genes are involved in lipid healthy controls. The functional
cause a newly described those observed in patients metabolism which suggests that consequences of Cdk10’s effect
disease characterized by severe with CDK10 mutations, or the impaired conversion of fats on cilia, however, remain to be
growth retardation, spine what has been termed Al Kaissi into energy may underlie the investigated.
malformation, dysmorphic Syndrome. “The mouse model growth retardation observed This study is a great example
facial features and intellectual provides compelling data that in mice and humans bearing of how mouse models contribute
disabilities, according to an CDK10 is the gene causing CDK10 mutations. This raises the to our understanding of human
international study led by disease, and confirms the potential for mitigating some of developmental disorders.
A*STAR researchers. human genetic data” said the features associated with Al “Without the mouse model that
The team found that nine Philipp Kaldis, at the A*STAR Kaissi Syndrome through dietary recapitulates some of the features
individuals from five unrelated Institute of Molecular and Cell interventions. of Al Kaissi Syndrome we would
families in Turkey, Algeria, Biology and lead author of not have uncovered a new role
Tunisia and Saudi Arabia with the study. “Without the for CDK10 in cilia growth and
identical clinical features all Despite Cdk10 being mouse model we metabolism” explains Kaldis.
carry mutations that inactivate an essential gene for mouse would not have Identifying the genetic causes
the cyclin-dependent kinase 10 development, fibroblast cells of rare conditions not only helps
uncovered a new
(CDK10) gene. Mutations are from Cdk10-deficient mice and physicians with diagnoses, but
role for CDK10 in
rare in CDK genes, which encode from patients divided normally offers researchers a starting point
proteins that regulate cell growth when isolated and grown in the
cilia growth and for developing new treatments.
and division and are carefully lab. However, analyses of various metabolism.”
kept in check to prevent tumor organs revealed multiple defects 1. Windpassinger, C., Piard, J., Bonnard,
C., Alfadhel, M., Lim, S. et al. CDK10
formation. in the mice lacking Cdk10. In the The expression of genes mutations in humans and mice
To investigate the effects of affected organs (which included involved in the formation of cause severe growth retardation,
© rubberball/Getty
losing the function of CDK10, kidneys, lungs, brain, intestine tiny hair-like, sensory cellular spine malformations and develop-
the researchers generated and muscle) more than 600 protrusions called cilia was mental delays. The American Journal
of Human Genetics 101, 391–403
mice lacking the Cdk10 gene. genes were expressed differently affected in organs of Cdk10- (2017).
These mice displayed severe compared with healthy control deficient mice — their fibroblasts
Persistent inflammation
in the liver in chronic viral
hepatitis has been only
partially explained, but
these findings show that
gut bacteria causes pro-
inflammatory immune cells
to accumulate in the liver.
1. Tan-Garcia, A., Wai, L. E., 1. Kong, L., Zhao, Y., Dasgupta, B., Ren,
Zheng, D., Ceccarello, E., Jo, Y., Kedar, H. et al. Minimizing isolate
J. et al. Intrahepatic CD206+ catalyst motion in metal-assisted
macrophages contribute to chemical etching for deep trenching
inflammation in advanced viral- of silicon nanohole array. ACS Applied
related liver disease. Journal of Materials & Interfaces 9, 20981–
Hepatology 67, 490–500 (2017). 20990 (2017).
CELLS NAÏVE
which are involved in regulating allowing ESCs to perpetuate
gene expression and modifying the stem cell pool and mature
the structure of chromatin, into any cell type — but that
Two proteins maintain embryonic stem cell the material that forms they did this through different
pluripotency through different means chromosomes. mechanisms.
© xxxxxxxxxxxxxx
PRDM14 helps keep stem ‘‘Our findings could details of what happens within Guccione and his colleagues
cells naïve by turning off a group be incorporated embryonic stem cells when three are now collaborating with
of genes, called DNMTs, which into the routine different signaling pathways are geneticists to investigate whether
code for a family of enzymes screening switched on and off, but much mutations in PRDM15 lead
that add methyl groups to DNA. strategies for remained unknown about the to developmental defects in
PRDM15, however, was not ‘upstream’ factors, including those humans. “We think our findings
families showing
involved in DNA methylation. discussed in this study, that affect could be incorporated into the
developmental
The team found that PRDM15 these pathways. Understanding routine screening strategies for
conserved the naïve state of ESCs
defects.’’ these signaling pathways is families showing developmental
by turning on genes involved important for determining defects,” he says.
in regulating two signaling distinct targets, have evolved optimal culturing conditions
pathways that communicate how to regulate similar pathways, for mouse ESCs, understanding 1. Mzoughi, S., Zhang, J., Hequet, D.,
Teo, S. X., Fang, H. et al. PRDM15
the cell should function. in a non-redundant fashion, to the cues that regulate normal
safeguards naïve pluripotency by
“I found it interesting, from prevent embryonic stem cell embryonic development in living
transcriptionally regulating WNT
an evolutionary standpoint, that differentiation,” says Guccione. organisms, and finding ways to and MAPK-ERK signaling. Nature
different members of the same Previous studies had reprogram the body’s cells to Genetics 49, 1354–1363 (2017).
family, which bind to completely determined ‘downstream’ regenerate other tissue types.
© Fotosearch/Getty
www.research.a-star.edu.sg
www.research.a-star.edu.sg A*STAR RESEARCH 23
CONTENTS | F E AT U R E S | RESEARCH HIGHLIGHTS | NEXT ISSUE
demonstrations show that Research explained that many 1. Dai, Z., Sufatrio, Chua, T-W.,
Balakrishnan, D. K., & Thing, V. L. L.
chat-app designers should messaging apps use ‘end-to- Chat-app decryption key extraction
end’ encryption — only the through information flow analysis.
improve the ways they protect sender and receiver can read Cryptology and Information Security
users’ personal data messages and they are encrypted Series 15, 3–18 (2017).
NEUROSCIENCE
WHAT A
HUNGRY FLY
CAN TELL US
ABOUT OBESITY
A*STAR researchers
have used brain cell
silencing technology
Understanding how to open new insights
into the role played by
a fly modulates its the brain in feeding
behavior.
feeding behavior could
help fight obesity
Turning various neural circuits “When we started this systems in genetically oxygen intake — which should
on and off in the brain of the project, I expected to find a lot of manipulated vinegar flies, have mirrored food intake —
vinegar fly could help A*STAR studies in this important area, but Drosophila melanogaster. actually decreased while food
researchers develop new was surprised to find just three “We used transgenes that intake increased.
treatments for obesity, diabetes, papers with five experiments. combine the fly’s own gene switch The group’s original
and heart disease1. Our study more than doubles with a protein that silences hypothesis was that
In changing external the available information.” electrical activity in neurons. disrupting neuromodulators
environments, animals, This way, we can shut off specific would have coordinated
including humans, maintain ‘‘We can shut modulator circuits and examine effects on feeding and other
a steady physiological energy off specific the effect this has on feeding.” aspects of physiology, but
state by altering both their modulator circuits The insects were then this was refuted — an outcome
internal metabolism and feeding assessed by monitoring that Claridge-Chang says
and examine the
behavior. If energy supplies 11 parameters: activity; could lead to important new
are low, for example, the brain
effect this has on climbing ability; individual insights. “The dissociation
produces hunger signals to
feeding.’’ feeding; group feeding; food of phenotypes implies that
drive food-seeking behavior to discovery; both fed and starved different modulatory circuits
replenish the animal’s reserves. “We wanted to know, if we respiration; fed and starved have disconnected or even
In a recent study, Adam turn off these different circuits, lipid content; and fed/starved oppositional effects on different
Claridge-Chang, and colleagues what will happen to the feeding body weight. physiological functions. We
© PLASTICBOYSTUDIO/Moment/Getty
from A*STAR’s Institute of behavior,” Claridge-Chang says. Claridge-Chang says the will test this hypothesis in
Molecular and Cell Biology “If we see a dramatic impact on results from these experiments future experiments.”
and the Singapore Institute of feeding, could that be a way of indicate that individual
Manufacturing Technology looked treating the compulsive eating neuromodulatory system effects 1. Eriksson, A., Raczkowska, M.,
Navawongse, R. Choudhury, D.,
at how inhibiting neuromodulator related to obesity?” on feeding behavior, motor
Stewart, J. C. et al. Neuromodulatory
cells that release dopamine and To find out, the activity and metabolism are circuit effects on Drosophila
serotonin would affect feeding and research team silenced five not related to each other. As an feeding behaviour and metabolism,
metabolic functions1. different neuromodulator example, in one experiment, Scientific Reports 7, 8839 (2017).
PRECISION
MACHINING
A microfluidic chip
injection mold.
A SMOOTHER
FINISH ALLOWS
FLUIDS TO FLOW
A magnetic method for
polishing metals enables
mold templates with
microscale features
are small and portable, easy to Injection molding involves known as magnetic field-assisted polishing. The polish reduced
use without expert knowledge, shaping a material while in finishing. Two magnetic rollers the roughness of the surface by a
and disposable because they a molten state using a metal rotating in opposite directions factor of four, leaving a mirror-
are cheap to produce. But template. It is cheap, fast, and on either side of the mold create like finish. “The next step will
this disposability means that useful for creating microfluidic a magnetic field. This field be to use the polished mold
microfluidic chips need to be chips. However, engineering a controlled a magnetic abrasive template for actual injection
quickly mass produced. mold with precise micrometer- made of carbonyl iron powder molding,” says Guo.
Now, Jiang Guo and his scale features and smooth and alumina particles bound
colleagues from the A*STAR surfaces is challenging as burrs together by oil, which removed 1. Guo, J., Liu, K., Wang, Z. & Tnay, G. L.
Magnetic field-assisted finishing of a
Singapore Institute of and tool marks create defects. A any unwanted material and mold insert with curved microstruc-
Manufacturing Technology post-polishing process can fix smoothed the surface. tures for injection molding of micro-
have developed a method for some of these imperfections, but The researchers compared fluidic chips. Tribology International
fabricating molds that can it is difficult for polishing tools their template before and after 114, 306–314 (2017).
it’s known that liver cells the cells’ defenses against HBV
contain factors that facilitate infection so that they can be
HBV replication, Ko and her used to test the efficacy of new
team found that the cells also drugs. “The reason for the very
VIROLOGY lack functional levels of the successful development of
proteins Slug and SOX7. These antiviral drugs for hepatitis C
proteins are found in most was the availability of robust,
other human tissues, where cell-based screening assays.
they bind to the HBV genome Hepatitis B has always been
and block the binding of the lacking in this area,” says Ren.
cells’ proteins that initiate and “When we introduce HBV into
HEPATITIS B promote viral replication. these Slug-deficient cell lines,
In the absence of
protective proteins
Slug and SOX7,
hepatitis B infection
thrives in liver cells,
© 2018 A*STAR Singapore Immunology Network
indicated by green
staining in this
image.
Reproduced from Ref. 1 and licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) © 2017 J. He et al.
memory of IgE responses. the memory of IgE responses.
The team injected mice with In a secondary allergic
one of two antigens, eliciting reaction, allergens bind to
a primary allergic immune IgE attached to the surface of
response. They then isolated a another type of white blood
type of immune cell from the cells, called mast cells, which
mice’s serum, called memory B then release chemicals to
cell, specific to IgG1. They found cause anaphylaxis. The team
three subsets of this memory hypothesize that low affinity IgE
B cell: double positive (DP), compete with high affinity IgE
single positive (SP) and double for space on the surface of mast
negative (DN) depending on cells, and may help limit severe
the types of receptors on their allergic reactions.
surface. These cells were then “This is an early phase
injected into mice that hadn’t study for this aspect of IgE
been previously exposed to and allergy,” says Poidinger.
the antigens; one of the two “Knowing how IgE memory is
antigens was administered, and generated, we can ask questions
a secondary allergic immune about drugs and preventative
response occurred. treatments.”
The researchers found that
Previously unexposed mice were first injected in their right ears with DP IgG1 memory B cells from 1. He, J. Subramaniam, S., Narang, V.,
DP or DN IgG1 B cells and then they were intravenously injected with an Srinivasan, K., Saudners, S. P. et
the donor mice — those that
antigen. Those injected with DP, on the left, showed a local anaphylactic al. IgG1 memory B cells keep the
reaction in their ear (blue). Those injected with DN, on the right, did not. held the memory for either of memory of IgE responses. Nature
This demonstrates that only the DP cells are producing high affinity IgE. the two antigens — produced, as Communications 8, 641 (2017).
CANCER
GENETICS
CLASSIFY
AND
CONQUER
Molecular dissection of
bile duct cancer reveals A schematic of the di-
gestive system including
subtypes with different the stomach (orange),
origins and varying liver (brown), gallbladder
(green), and the bile duct
potential treatments (green tubes).
Researchers have discovered that the team investigated the Centre Singapore, one of the in the methylation patterns
cholangiocarcinoma (CCA), a genomic sequences of the tumors study’s senior authors. offer clues about the processes
form of liver cancer also known as and their epigenomic and gene One of the clusters was acting in each cluster. “Based on
bile duct cancer, consists of several expression profiles. They divided characterized by changes in molecular data, we can speculate
molecular subtypes with distinct the cancers into four groups with genes associated with immune about the different mechanisms
potential therapies and prognoses. different patterns of mutations response, suggesting that leading to different DNA changes
An international and other genetic defects, two it might be a candidate for in the development of CCA. You
collaboration led by Patrick of which were associated with immunotherapy treatment. really can’t see that from just the
Tan of A*STAR’s Biomedical liver-fluke infection. “The Likewise, the characteristics of anatomical information,” says
Research Council, analyzed current way of classifying CCAs some of the tumors indicated that co-lead author Chern Han Yong.
tumors collected from almost is by their anatomical subtype. they might respond to therapeutic These findings demonstrate
500 bile duct cancer patients Our data shows that if you look interventions currently in use that distinct molecular subtypes
in 10 countries, in a study that at molecular data, you get more or under development. “We’ve can result from different
is part of the International clinically relevant subtypes that shown that about a third of the cancer triggers. Learning
Cancer Genome Consortium. have different potential therapies patients can be treated using more about these subtypes and
By examining a large, diverse and prognoses,” says Bin Tean existing therapies, if experimental how they link with various
group, the researchers were able Teh of the National Cancer drugs were included it would carcinogenic processes may
to uncover patterns missed in be even more”, says lead author, reveal the mechanisms behind
earlier investigations, such as Apinya Jusakul. Currently, these cancers and guide the
‘‘About a third
one that included only North surgery is the only treatment for development of therapeutic
American patients, all of whom
of patients can bile duct cancer. interventions.
were free of the liver-fluke be treated using The molecular clusters
© Stocktrek Images/Getty
infection that is a common existing therapies, can also guide researchers in 1. Jusakul, A., Cutcutache, I., Yong, C. H.,
frequency’ (ENF) of power member Lilei Zheng. “As Singapore Police Force.
leaving unique fingerprints
in audio files that can help
grids is centered around 50 a consequence, recordings
© xxxxxxxxxxxxxx
or 60 Hertz, and is picked captured in different places at 1. Zheng, L., Zhang, Y., Lee, C. E. & Thing,
investigators identify the
V. L. L. Time-of-recording estimation
time of recording. up in audio recordings as a the same time will have ENF for audio recordings. Digital
background hum. The ENF fingerprints showing the Investigation 22, S115-S126 (2017).
shifts up and down randomly, same fluctuations.”
NEUROSCIENCE
DIVERTING
DISTRACTION
To avoid getting sidetracked
by distractions, neurons in the
brain’s short-term memory center
Electrical signals in the brain’s short-term memory center (as shown above), located in
reorganize their activity patterns the prefrontal cortex, morph when faced with distracting stimuli.
The ability to remember schizophrenia and dementia, were shown a grid on a screen This was not the case in
something like a grocery list or all of which involve memory and trained to remember the the frontal eye field, however.
telephone number even under deficits. location of a red square that There was no evidence of
bombardment from loud noises, The brain’s center for flashed briefly, without getting code-morphing ability in this
incoming text messages or other short-term memory storage sits thrown off by the subsequent visual part of the brain. This
distractions requires an intricate behind the forehead in the lateral flash of a green square. told the researchers that there
shape-shifting act in the brain. prefrontal cortex. The neurons Each monkey had a suite was something special about
A Singaporean team has there were once thought to be of electrodes implanted in the short-term memory retention
found that the neuronal response unaffected by disruptions, but brain, both in the prefrontal in the prefrontal cortex. They
patterns responsible for retaining Libedinsky’s team has shown cortex and in the frontal eye traced this cognitive capacity to
short-term memories reorganize otherwise. field, a nearby region involved a unique set of neurons with the
into a different configuration in in controlling visual attention ability to multitask.
the face of distracting stimuli There is and eye movements. This “These results will be
— a process dubbed ‘code- something allowed the researchers to track of interest to researchers
morphing’. special about neuronal activity as the monkeys in a number of fields,” says
“This code-morphing short-term performed the memory test. Aishwarya Parthasarathy, a
capability may be an important The team found that neurons postdoctoral research fellow at
memory
factor underlying cognitive in the prefrontal cortex became A-STAR and the study’s first
flexibility,” says Camilo
retention in activated following the initial author, noting that all areas of
the prefrontal
© 2018 A*STAR Institute of Molecular and Cell Biology
GETTING TO
THE ROOT OF
HAIR LOSS
The age-old search for
a cure for hair loss may
be close to an end
Understanding the energy In particular Dawson’s hair — only a small change in The team also uncovered a
it takes to grow a strand of hair team is examining the role that metabolism makes a noticeable previously unknown region in
could hold the key to ensuring mitochondrial metabolism and difference.” the hair shaft which they called
women, in particular, end their its by-product, reactive oxygen, Hair growth is an energy- the ‘ring of fire’ because it is a
lives with a wonderful bouffant. play in the bioenergetics of the intensive process, Dawson says, major source of reactive oxygen
Recent research by A*STAR hair follicle. with an average human growing species.
scientist Thomas Dawson and almost two meters of hair over Dawson says this study
his team, in collaboration with their body per hour. shows that hair follicles and
“People who
researchers from the Medical “It takes about 670 kilojoules growth are more complex
University of South Carolina
go on crash of energy to grow one gram of than previously thought, and
Pharmacy School Department diets, students hair, which is the equivalent of that quelling the formation of
of Drug Discovery, suggests that undertaking six minutes of intense exercise reactive oxygen species and
the slowing of the metabolism exams, all will using both arms and legs,” maintaining mitochondrial
as we age could be a driver of lose hair — only Dawson points out. metabolism could be key to
‘chronogenetic alopecia’ or age- a small change He believes the cells that improving hair quality as we age.
related hair loss, a condition that in metabolism create the hair multiply and “If we use materials such
predominantly affects women. makes a synthesize biomass so quickly as leave-on creams or lotions
Dawson, from A*STAR’s noticeable that they burn enormous that alter metabolism you can
Institute of Medical Biology, says difference.” amounts of energy much like change the way hair grows and
that the majority of hair research “driving a car with both feet make follicles survive longer and
© 2018 A*STAR Institute of Medical Biology
to date has focused on balding down hard on the gas”. produce better hair.”
men — even medical books “As we age mitochondrial “The motor is running
from Cleopatra’s reign contained energy production slows, so we absolutely flat out and as a 1. Lemasters, J, Ramshesh, V. K.,
Lovelace, G. L., Lim, J., Wright, G.
formulas to cure hair loss. end up with a reduced ability to result there is excess reactive D., Harland, D. & Dawson, T. L. Jr.
His latest study uses cutting- make good hair,” he says. “Any oxygen generation in the hair Compartmentation of mitochondrial
edge laser microscopy on plucked time there is a screw up in your follicle that actually damages the and oxidative metabolism in growing
human and bovine hair to better metabolism you lose hair. People structure. The follicle then loses hair follicles: A ring of fire. Journal
of Investigative Dermatology 137,
understand hair growth at a who go on crash diets, students its ability to continue to operate 1434–1444 (2017).
molecular and metabolic level. undertaking exams, all will lose at full form over time.”
a 10μm
1 3
2 4
PHOTONICS
b
TE, 1520nm
A SIMPLER PATH
A fresh design approach greatly
simplifies a key component of TE, 1570nm
photonic circuits by optimizing
the coupling of straight and
curved light paths
TE, 1620nm
An electron micrograph of the fabricated coupler (a), and -10 -5 0 5 10
the optical energy in the two waveguides (b). μm
A core element of circuits A broadband “However, it has been very Ong’s team came up with
handling optical signals can now coupler that difficult to try to make them a design methodology based
Modified from Ref. 1 and licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) © 2017 G. Chen et al.
be made smaller and simpler, and provides reliable compact, with low power loss on a mathematical ‘transfer
with functionality over a wider performance over and broadband operability, using matrix method’ to determine the
range of wavelengths, because of a wide range of standard processes.” coupler section lengths, radii,
a mathematical model developed useful wavelengths A coupler works by running and waveguide cross-sections
by A*STAR researchers1. The a second optical path, known that would give the desired
is something
new design methodology is as a waveguide, alongside the operation with low wavelength
expected to have widespread use
of a holy grail signal path. The optical signal sensitivity. Using this approach,
in photonic integrated circuits
for photonics induces a secondary signal in the the team designed and fabricated
and contribute to more compact engineers. adjacent waveguide, passing with a 50/50 power splitter with a
photonic devices. it some of the signal’s energy. wide bandwidth and length of
Optical signals, such as To overcome this obstacle to However, the ratio of power just 20 micrometers.
those transmitted over optical photonic circuit miniaturization, splitting changes depending on “We were able to improve
fiber, require photonic elements Jun Rong Ong and colleagues the wavelength of the signal, so a the broadband performance
and circuits to be useful. One from the A*STAR Institute of broadband coupler that provides of the photonic power splitter
of the most important photonic High Performance Computing, reliable performance over a wide through a simple modification
functions is ‘coupling’, which in collaboration with researchers range of useful wavelengths is of existing designs, and have
allows the signal to be split into from the Singapore University something of a holy grail for achieved a balanced 50/50
two different paths or used to of Technology and Design, went photonics engineers. output which is difficult by
drive other dependent circuits. back to the drawing board to find “We distilled the key other designs,” Ong says.
Coupling, however, is generally a simpler approach to designing ingredient that makes a
only reliable over a narrow these critical coupling elements directional coupler a broadband 1. Chen, G., Ong, J.R., Ang, T.Y.L., Lim,
S.T., Png, C.E., & Tan, D.T.H. Broadband
band of wavelengths, for broadband operation. splitter – a combination of silicon-on-insulator directional cou-
demanding a complicated “Couplers are the basic straight and bent waveguides plers using a combination of straight
design and fabrication process building blocks of photonic – and thoroughly explored and and curved waveguide sections.
and bulkier circuits. circuits,” explains Ong. exploited it,” says Ong. Scientific Reports 7, 7246 (2017).
could shed light on the for potential threats and pass found one very significant
immunological mechanisms that information to the T cells difference; fetal dendritic
underlying fetal-maternal and B cells to ward off those cells over-express an enzyme
health problems such as pre- threats. called arginase-2,
eclampsia. which is known
“People thought that to block the T
“People thought
the fetal immune system cell secretion
was defective because it
that the fetal of a key
was not mature, but we’ve immune system inflammatory
discovered that it’s highly was defective signaling
dynamic, highly functional, because it was not molecule
and in fact represents another mature, but we’ve called TNF-
specialization,” says Florent discovered that it’s
Ginhoux, from the Singapore highly dynamic,
Immunology Network at functional and
A*STAR, who co-led the represents another
study with Jerry Kok Yen specialization.”
Chan from the KK Women’s
ESCAPING SILICON
SEMICONDUCTOR An alternative fabrication scheme for microscale
LASERS
semiconductor lasers could expand the applications
of on-chip lasers beyond conventional silicon
at the A*STAR Data Storage “We needed to develop a They do this by taking light performance in terms of facet
Institute have been working generic integration scheme that produced by a stack of ultrathin reflectivity, minimum lasing
on as a next-generation data would allow us to fabricate laser layers of a light-emitting current, emission efficiency and
storage technology. HAMR devices on different substrates, semiconductor (in this case output power.
uses integrated lasers for fast not just silicon,” says Lee. “For aluminum-gallium-indium- “We expect our results to
and precise micro-spot heating this, a facet reflector structure arsenide), and multiplying light serve as benchmark for research
of a magnetic medium, but is very useful, but low facet at the target wavelength using a and development on etched facet
requires the laser to be formed reflectivity is a problem, and resonant cavity formed between lasers with different reflectors,”
on aluminum-titanium-carbide using different reflectors usually two reflectors. says Lee.
(AlTiC) rather than silicon. This means a more complicated By designing a faceted laser
presented Chee-Wei Lee and fabrication process and greater structure considering process 1. Lee, C.-W., Ng, D. K.-T., Ren, M. Fu,
Y.-H., Kay, A. Y. S. et al. Comparison
his colleagues with a significant chance of device failure.” integration, Lee and his team of III-V/Si on-chip lasers with etched
problem, since the silicon The lasers used in such developed a fabrication scheme facet reflectors. Applied Optics 56,
substrate plays in integral role in applications turn electrical that can accommodate different 5086–5091 (2017).
Computer-generated imagery of an
abnormal growth in the colon. A*STAR
scientists have now provided compelling
evidence that metformin might be
a useful clinical agent to treat such
© xxxxxxxxxxxxxx
life-threatening malignancies.
Biological Resource Centre, high glucose, insulin, and explain this. Further clinical
and the Genome Institute of growth factor levels are needed trials are now needed.”
Singapore, with collaborators to establish cell cultures for
from hospitals across Singapore, injection. Tan’s group suspects 1. Suhaimi, N-A. M., Phyo, W. M.,
Yap, H. Y., Choy, S. H. Y., Wei, X.
have now tested metformin’s that this artificial environment
et al. Metformin inhibits cellular
cancer-fighting abilities on a meant previous studies needed
proliferation and bioenergetics in
model of colorectal cancer that higher levels of metformin colorectal cancer patient-derived
is more representative of how the to stunt tumor growth as, in xenografts. Molecular Cancer
disease appears in humans. this study, they were able to Therapeutics 16, 2035–2044 (2017).
and female mice that each adulthood and became hormone, it could be developed eclampsia and those with normal
carried only one copy of the pregnant, they showed high into a drug as is insulin for blood pressure.
ELA-coding gene to produce blood pressure and protein in diabetes,” Reversade says.
‘knockout’ mice. Around half their urine, classic signs of pre- This discovery also opens up 1. Ho, L., van Dijk, M., Tan Jian Chye, S.,
Messerschmidt, D. M., Chng, S. C. et
of these knockout mice showed eclampsia, while their fetuses the possibility of using ELA, or al. ELABELA deficiency promotes
severe embryonic cardiovascular also had the lower birth weight more specifically the observation pre-eclampsia and cardiovascular
malformations and did not typical of babies born to of lower ELA levels, to enable malformations in mice. Science 357,
survive to birth. Despite their mothers with the condition. early diagnosis of pre-eclampsia, 707–713 (2017) .
NANOPARTICLES
Unlocking the molecule- the nanoparticles inside the in positioning. For example, equilateral to right-angled
detecting capabilities of templates pushing them to their elongated liquid ‘fingers’ triangles revealed the potential
gold nanoparticles often target locations. within square templates forced of asymmetrical patterns — up
requires positioning techniques Mohamed Asbahi from the nanoparticles to move to to three nanoparticles could
that are beyond the limits of Institute of Materials Research corners where the solvent be trapped and positioned at
conventional lithography. and Engineering at A*STAR volume is the largest. various nanoscale separations in
An A*STAR team now recalls trying to control self- right-angled templates.
demonstrates that a combination assembly within square-shaped “We were Further experiments
of topographical templates templates when he and his surprised by this demonstrated that particular
and localized traps left by co-workers made an intriguing liquids can have different
effect before we
evaporating liquids can fabricate discovery. “We were increasing impacts on nanoscale patterns.
understood the
arrays of nanoparticles with cavity sizes in the templates, While toluene tends to ‘pin’
controllable separations below and expected to see more
physics behind it.” to the template structure and
five nanometers1. nanoparticles inside trying to trap nanoparticles at lower-
Left alone, nanoparticles optimize their arrangement,” “We were surprised by than-normal densities, hexane
tend to agglomerate due to he says. “But with toluene as the this effect before we understood solvents produce fully-packed
their high entropy. Because solvent, only four nanoparticles the physics behind it,” says surfaces. Asbahi notes that
© 2018 A*STAR Institute of Materials Research and Engineering
keeping gold nanospheres set were trapped at each corner of Asbahi. “But after we predicted the control offered by this
distances apart is critical for a square — no matter how large irregular cavities were technique could be sufficient
applications, including optical the cavity.” more successful at directing for integration into prefabricated
bioimaging, researchers are To explain this behavior, nanoparticles than equilateral circuits and plasmonic
developing ways to fabricate the researchers developed ones, we chose to validate nanostructures.
hundreds of thousands of these a virtual model to simulate our explanations with
objects automatically. One interactions between the triangular templates.” 1. Asbahi, M., Dong, Z., Wang, F.,
Saifullah, M. S. M., Yang, J. K. W. &
promising route, known as deposited nanoparticles and Working with state- Chong, K. S. L. Second order
directed self-assembly, deposits solvent within confined cavities. of-the-art electron beam directed positioning of nanoparticles
liquid suspensions of reagents These computations showed that lithography, the researchers induced by the main terminal
on to substrates with predefined after the liquid begins drying fabricated templates containing meniscus shape in irregular
template cavities. Nanoscale 9,
small-scale patterns. Liquid out, the shape of the retreating thousands of triangles just a few 9886–9882 (2017).
capillary action then draws interface played a key role nanometers in scale. Comparing
ADVANCED
MATERIALS
PICKING
WINNERS FROM
MILLIONS OF
POSSIBILITIES
A clever simulation scheme
helps identify the most
promising compositions of
two-dimensional materials
A high-throughput scan arrangements of transition are huge. So we developed a alloy structures,” says Tan.
of possible compositions for a metals (like molybdenum or high-throughput computational The scan, conducted in
new class of materials known titanium), carbon and nitrogen. method to predict the probable collaboration with Drexel
as MXenes gives researchers These characteristics are reflected structures and stable phases of University in the US, revealed
invaluable direction for picking in the name ‘MXene’ — the ‘M’ different MXene alloys across that molybdenum-based MXenes
the best candidate from the represents metal atoms, the ‘X’ all compositional ranges and mixed with vanadium, tantalum,
millions of possible material denotes carbon and nitrogen, temperatures.” niobium or titanium, appear to
recipes1. The simulation study while the ‘ene’ suffix signals the Although there are form the most stable ordered
by researchers from the A*STAR materials’ 2D atomic structure. many possible MXene alloy structures. Titanium however
Institute of High Performance compositions, most will not be tends to form stable ‘asymmetric’
Computing is a significant “Our approach stable. The challenge faced by ordered structures that were
advancement in the field of enables quick material scientists has been how previously not considered viable.
MXenes, which have exciting evaluation of the to efficiently sweep through “Our scan allows us to predict
potential in next-generation the huge number of alloy the structures of MXene alloys
formation energies
energy storage applications. configurations to identify those that are yet to be fabricated
Two-dimensional (2D)
of millions of MXene with the lowest formation energy and estimate the likelihood
materials are a relatively new
alloy structures.” and hence highest stability. of their fabrication from a
class of materials that display a Conventional ‘first principles’ thermodynamics viewpoint. And
wide range of unusual properties “Since MXenes are new, calculation approaches are too for known MXene alloys, our
associated with their ability there’s still much to be learned computationally intensive for predicted structures are consistent
to constrain the movement about their structure and such a scan to be feasible. with experimental results.”
of electrons and energy in a properties,” says Teck Leong Tan “Our approach uses what’s
©onurdongel/E+/Getty
2D plane. The MXene alloys from A*STAR. “As MXene alloys called a cluster expansion method 1. Tan, T.L., Jin, H.M., Sullivan, M.B.,
Anasori, B., & Gogotsi, Y. High-
are a very recently discovered are formed by mixing different to ‘learn’ the effective interactions throughput survey of ordering
class of 2D materials, which types of transition elements between atoms, thus enabling configurations in MXene alloys across
could conceivably consist of at different compositions, the quick evaluation of the formation compositions and temperatures. ACS
any of millions of possible alloying possibilities in MXenes energies of millions of MXene Nano 11, 4407–4418 (2017).
ENGINEERING
Flexure
MAKING LIGHT
WORK OF Fine Stage
NANOPOSITIONING
An integrated design strategy
Interferometer
lowers the mass and costs of
motors that move objects nano- An integrated nanopositioning device can achieve high precision with a simpler and less expensive
meters at a time design than typically used.
Probing intricate cells or This type of configuration, can be controlled with the same applied force ‘ripples’ through
high-tech microchip components known as serially-actuated electromagnetic machinery the nanopositioner and impacts
requires ‘nanopositioners’ dual-stage design, has inherent used to drive the coarse motor small-scale movements.
that can scan large areas with problems according to Daniel — eliminating the weight and Fabrication of an
extremely small steps. Normally, Tat Joo Teo from the Singapore expense of troublesome cables. experimental prototype revealed
these positioners have separate Institute of Manufacturing the potential of the researchers’
fine- and coarse-movement Technology (SIMTech) at A*STAR. “The parallel- integrated positioner and
stages, but A*STAR researchers “In a traditional serially-actuated actuated dual- analytical model. As measured by
have introduced a parallel- design, power cables are linked to stage design gives a laser interferometer, the device
actuated system that integrates the fine-motion stage to energize could move in 20 nanometer
reasonably good
the two units for improved the actuators. These cables cause steps without being sensitive
performance even
energy efficiency1. substantial disturbance, and limit to millimeter-scale coarse
When engineers design the performance of the entire
with a low-cost movements — findings that may
bearings for guiding moving motion system.” coarse stage.” usher in a new era of inexpensive
parts, they typically work with Teo and his collaborators nanopositioning devices.
tolerances of a few micrometers. from SIMTech and the National The challenge with this “The parallel-actuated dual-
Nanopositioning devices, University of Singapore integrated design, notes Teo, lies stage design gives reasonably
however, need precision considered a different approach in finding the right combination good performance even with
© 2017 IEEE. Reprinted, with permission, from Ref 1.
standards up to a thousand times to constructing nanopositioners. of mechanical characteristics a low-cost coarse stage,” says
greater. To achieve this kind of Instead of conventional such as stiffness and damping. Teo. “We plan to commercialize
precision motion, piezoelectric piezoelectric actuators, they While conventional positioners the system to benefit our
crystals that slightly expand or chose a magnetic linear motor can analyze the properties manufacturing industry.”
contract with voltage stimulation as a means to establish fine of controllers, actuators, and
are usually combined with an motion. Then, they coupled this mechanical stages independently, 1. Zhu, H., Pang, C. K. & Teo, T. J. A
flexure-based parallel actuation
active feedback sensor. Then, the motor with hinge-like flexure the team had to find a way to
dual-stage system for large-stroke
fine-motion crystal is mounted bearings attached to the coarse optimize these three elements
nanopositioning. IEEE Transactions
on to the moving part of a translator. The flexure system concurrently. To do so, they on Industrial Electronics 64, 5553–
linear actuator capable of large offers nanometer-scale movement established an analytical model 5563 (2017).
displacements in a single stroke. without dry friction and critically, capable of predicting how
FLAT-PACKED
OPTICAL COMPONENTS
OPTICS
Nanostructured thin-films that can bend light by large angles
could be a replacement for bulky glass optical components
chosen properties. This can, “Our new approach goes beyond that the wavelength of the small objects or features.”
for example, be used to bend the standard design, which is to incident light. With this novel
the incoming beam into a use phase mapping,” explains approach they were able to bend 1. Khaidarov, E., Hao, H., Paniagua-
Domínguez, R., Yu, Y. F., Fu, Y. H.,
new direction. However, the Paniagua-Domínguez. “We more than 50 per cent of the Valuckas, V., Yap, S. L. K., Toh, Y. T., Ng,
efficiency with which the light foresee that these metasurfaces energy of an incoming beam J. S. K. & Kuznetsov, A. I. Asymmetric
is redistributed into the correct may out-perform traditional of green light at an angle of up nanoantennas for ultrahigh angle
direction decreases sharply bulk optics not only in terms of to 73 degrees. Moreover, and broadband visible light bending.
Nano Letters 17, 6267–6272 (2017).
for increasing angles, making efficiency, but also functionality.” contrary to previous approaches,
new questions. centrosomes, when they noticed of microtubules in the cells and a in that cell and in the sister cell
“This was a chance discovery. that neighboring cells were change in cell shape. Destroying connected to it?”
It’s not something we or others connected by microtubule the MTOC in other cells has
could have hypothesized based bridges. Microtubule bridges similar consequences, suggesting 1. Zenker, J. White, M. D., Templin, R. M.,
Parton, R. G., Thorn-Seshold, O. et
on previous work,” says Nicolas usually form between dividing to the team that the bridges may al. A microtubule-organizing center
Plachta of A*STAR’s Institute cells during mitosis, but substitute for the MTOC in the directing intracellular transport in
of Molecular and Cell Biology, they are normally broken early embryo. the early mouse embryo. Science
who led the study. A structure down afterwards. “But these Further observation revealed 357, 925–928 (2017).
HIGH-
RESOLUTION
PRINTING
N4 te
Si 3 s tra
b
Su
Si
FLOATING
NANOSTRUCTURES 20 µm
FOR BETTER COLOR
(above) A schematic of the surface
the team created featuring tiny silicon
nanostructures.
Extremely high-resolution color images are
(left) The team’s reproduction of
produced using silicon nanostructures that Kandinsky’s Murnau Street with Women.
The detail in color images is five years, and now we have 70-nanometer silicon nitride nanodisks, as well as nanorings,
limited by the size of pixel that solved the problem of limited layer. The nitride acts as an ‘anti- on their substrate, until they
can be printed. Recent advances color saturation,” says Yang. reflective’ coating, effectively were able to achieve high-
in nanotechnology have opened Unlike previous efforts with tricking the incident light into resolution images with over
the possibility of printing at nanostructures made from behaving as if it is not there and 120 per cent of the sRGB color
incredible resolutions of around precious metals such as silver the nanodisks are floating in free palette — the best quality
100,000 dots per inch, by using and gold, the team used space. color from any nanostructure
metallic nanostructures that silicon, which is cheap, readily “An important requirement system of this resolution. They
resonate in response to incident compatible with existing for ideal color reflection is to demonstrated the system by
light. However, the colors that electronics, and has useful meet Kerker conditions, where accurately reproducing a print
these systems produce are optical properties. incident light excites magnetic of Wassily Kandinsky’s
limited, and cannot fill the and electric dipoles in a silicon famous painting Murnau
standard Red Green Blue (sRGB) “We have been particle in such a way that the Street with Women.
palette used in most devices and working on ultra- particle scatters light entirely Yang and Dong are hopeful
the Internet. high resolution in one direction,” explains that their new design for
© 2018 A*STAR Institute of Materials Research and Engineering
Now, a team including Joel color printing for Yang. “In free space, the nanostructure printing could
Yang, Arseniy Kuznetsov and uniform surroundings of eventually be accessible to
the past five years,
Zhaogang Dong at the A*STAR the particle allow Kerker everyone via a desktop device,
and now we have
Institute of Materials Research conditions to be met. A and could also have applications
and Engineering (IMRE), and
solved the problem substrate will generally in miniaturized displays, data
Data Storage Institute (DSI) have of limited color break spatial symmetry, but storage and security prints for
produced a new printing system saturation.” if the substrate does not reflect, identifying counterfeits.
with nanostructures made from the situation is equivalent to
silicon, achieving a spread of The researchers used light propagating through 1. Dong, Z., Ho, J., Yu, Y. F., Fu, Y. H.,
Paniagua-Dominguez, R. et al.
colors even wider than sRGB1. electron-beam lithography free space.” Printing beyond sRGB color gamut
“We have been working and reactive-ion etching to Yang, Dong and co-workers by mimicking silicon nanostructures
on ultra-high resolution produce tiny silicon disks, experimented with several in free-space. Nano Letters 17,
color printing for the past 130 nanometers high, on a different sizes and spacings of 7620–7628 (2017).
© Image Source/Getty; © 2018 A*STAR Institute of Medical Biology; Reprinted from X. Fan et al., Polymer Chemistry 8, 5611 (2017) with permission of The Royal Society of Chemistry; © RICHARD KAIL/Science Photo Library/Getty
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