Professional Documents
Culture Documents
SUPERBUGS
MEET THEIR NEMESIS
Polymer could avert global
antibiotics crisis
page 8
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E D ITO R IA L
3 Notes from the editors
FE ATU R E S &
I N N OVATI O N S
4 Charging forward with the battery
revolution
COVER STORY
8 Beating bacteria
– looking beyond antibiotics
R E S E A RCH
H IG H LIG HT S
12 Spin memory: Dynamic solution
for accurate reading
14 Obesity: High-fat diet linked to
4 F E AT U R E S &
I N N O VAT I O N S skin conditions
15 Cancer: The stomach’s ‘chief’
source of stem cells
16 Immunology: Newly identified cells
in liver protection role
17 Materials: Nature inspires light,
robust lattice structures
COVER STORY
18 Cells: Glaring lessons on skin aging
19 Microbiome: Gut bacteria affect
the brain, even in the womb
20 Laser spectroscopy: Measurements
through entanglement
20
tool empowers the people
30 Cancer treatments: Understanding
individual immune responses
R E S E A RCH
H IG H LIG HT S
31 Printing: Tiny droplets for
big color impact
32 Therapeutics: Engineering a safer
antibody drug
33 Cancer: A sustainable source of
natural killers
34 Lithography: A bright idea for
on-demand nanopatterns
35 Immunology: Monocytes in the mix
36 Cancer: Relocated enzymes make
cancer more mobile
38 Drug delivery: Reach for the stars
39 Cancer research: A blood test for
cancer recurrence
40 Ultrafast lasers: New approach to
generating ultrashort pulses
41 Photonics: Light-bending
nano-patterns for LEDs
42 UV protection: Lignin’s strengths in
smaller packages
43 Laser: Pulses of light with a tilt and
32 a twist
44 Cancer therapeutics: Targeting
the root of the problem
46 Rehabilitation: An adaptive
approach to stroke recovery
47 Genetics: Mutation linked to rare
skin disease
48 Proteomics: Turning up the heat
on protein interactions
46 COVER STORY
49 Oncology: Cloned tumors used for
a cancer crystal ball
50 Cancer biology: The molecular
path to better oral cancer care
51 Catalysis: Porous silica protects
nickel catalyst
NEXT ISSUE
52 A sneak peek of Issue 12
36 48
2 A*STAR RESEARCH Issue 11 | April – June 2018
CONTENTS | F E AT U R E S | RESEARCH HIGHLIGHTS | NEXT ISSUE
A
ntibiotic resistance has We also have many more stories BIG DATA
emerged as one of the biggest from diverse areas of research, such as: • A fully automatic web-based system has
threats to global health, as been developed that empowers non-
bacteria acquire resistance STEM CELLS experts to analyze big data (page 28).
faster than new antibiotics can be • A subpopulation of chief cells that can • Another team have devised a novel
developed. Scientists have recently become stem cells in response to injury approach to predict cancer drivers with
developed a polymer that can kill has been identified, shedding light on improved accuracy, and made their
bacteria effectively without triggering how the stomach lining renews itself, tool freely available online (page 22).
the evolution of resistance, which could and how gastric cancer begins (page 15).
be the key to averting the antibiotic • Researchers have found a way to NANOSTRUCTURES
resistance crisis (page 8). generate large numbers of ‘universal’ • Scientists have found a way to assemble
Our second feature looks at solving natural killer cells from induced quantum dots into nanoscale grids
a very different problem that plagues pluripotent stem cells, for applications using focused electron beams, for
us on a daily basis – that of battery such as immunotherapies (page 33). applications ranging from biosensors
capacity. Lithium-ion batteries essentially to solar panels (page 41).
power our daily lives – from mobile CANCER TREATMENTS • A new printing technique based on sil-
phones to electric cars, and even entire • A single-base mutation has been icon nanostructures has been invented,
homes in some cases – but they are fast discovered that can strongly predict which could achieve resolutions of up
approaching their physical limits. Two whether an oral cancer patient will to 100,000 dpi (page 31).
award-winning A*STAR researchers are respond to specific treatments (page 50).
exploring an alternative – lithium-sulfur • Scientists have also devised a method For our latest stories, please visit
batteries, a 50-year old technology that to grow miniatures of patients’ tumors us at https://research.a-star.edu.sg/ or
can potentially provide energy densities in the lab, which could help doctors follow us on Twitter at: @astar_research.
up to five times that of lithium-ion choose the most effective treatments We hope you will enjoy reading the rest
batteries (page 4). for individual patients (page 49). of this magazine.
Lithium-sulfur
batteries could
outperform
lithium-ion batte-
ries. [page 4]
SUPERBUGS
MEET THEIR NEMESIS
Polymer could avert global
antibiotics crisis
page 8
COVER IMAGE
Antimicrobial resistance is
© Andrey Suslov/Getty
CHARGING
FORWARD
WITH THE BATTERY REVOLUTION
Imagine energy densities five times that of lithium-ion
batteries. An A*STAR team is leading the race to bring
lithium-sulfur batteries to the masses
T
he desire to super-charge
increasingly smart, portable
electronic devices using
more efficient, large-capacity
batteries is palpable. “We hear
very sensational reports. For example, that
(Bottom) © boonchai wedmakawand/Getty Images
theoretically do, we are exploring Like all batteries, lithium-ion materials. A lithium-ion battery’s the need for ions to be inserted
drastically different, revolutionary and lithium-sulfur batteries store anode is generally made from into electrode materials means
battery technologies.” energy in the form of chemical graphite, and the cathode from that the theoretical energy
energy, which is converted a mix of expensive metal oxides density of a sulfur-lithium
are competing to develop cheaper, but have two to four BATTERIES materials. But we hope to start
prototypes of lithium-sulfur times greater charge capacity. CAN’T making coin cells over the next
batteries, Zheng last year set Using these materials could also HANDLE, 5–10 years and then build bigger
up a company called Coulomb help avoid the issue of dendritic SUCH AS GRID cells that can really impact
Innovation in Singapore with deposits, which are caused by our lives.”
a friend to commercialize the reactivity of lithium metal
STORAGE FOR
lithium-sulfur technology, with and eat away at the effectiveness SOLAR AND For references, visit the online
a focus on material production. and lifetime of the batteries. WIND ENERGY version of this article at:
www.research.a-star.edu.sg/
Zheng is now preparing to However, magnesium and STORAGE. feature-and-innovation/7886
BEATING
BACTERIA
– LOOKING
BEYOND
ANTIBIOTICS
Genome specialists and bioengineers
have come up with a polymer to
fight superbugs, which could help solve
the world’s antibiotics crisis
T
he standard SERENDIPITY: HOW introduced to the bloodstream,
treatment for a COMPUTER HARDWARE LED while leaving human cells alone.
serious bacterial TO INFECTION TREATMENTS Today, Hedrick, the lead scientist
infection is a Last year, the World Health for IBM Research’s advanced
dose of antibiotics, Organization (WHO) released organic materials group, is one of
which slow or halt the a list of 12 of the world’s most Yang’s main collaborators.
infection by hindering critical dangerous superbugs — a move Since then, Yang and a
cellular processes within intended to underline them as the handful of other researchers have
the bacteria. However, some highest priorities for antibiotic looked at various polymers, but
bacteria have evolved devious research. Marie-Paule Kieny, each new iteration encountered
mechanisms to protect the WHO’s assistant director- problems. Biodegradability is one
themselves against antibiotics, general for health systems, was — without a route for excretion,
for instance by producing pointed in a WHO communiqué: non-biodegradable polymers
enzymes that can destroy “If we leave it to market forces could build up in a patient’s body,
the antibiotic molecules, or alone, the new antibiotics we potentially causing problems.
by making themselves less most urgently need are not going Yang’s new polymer is broken
permeable to the antibiotic. to be developed in time […] down via a chemical reaction
The most resilient become The pipeline is practically dry.” with water, the products of which
better at this every time they’re However, a treatment that kills are excreted within days, meaning
exposed to the drugs. The class bacteria and doesn’t stimulate it’s a much more promising
of multi-drug resistant bacteria resistance could represent candidate for drug development.
that have become the most a new chapter in the fight In 2016, a University of
difficult, or, even impossible to against superbugs. Melbourne study published in
treat, are known as superbugs. Yang was aware of the Nature Microbiology attracted
Last year, a UK government problem when her team attention when it found a similar
report suggested that, by started their polymer work, but lack of drug resistance in their
2050, drug-resistant infections superbugs also just pique her polymer. Newspapers put a
could kill one person every curiosity. Bacteria, she says, are positive spin on the fact that it
three seconds. not unlike our own mammalian “ripped the bacteria apart”. But
In March 2018, a team cells in their ability to develop Yang says that, actually, this is
working under Yi Yan Yang, and learn. “They’re very smart.” not really a good thing. “With
a bioengineer from the If bacteria were in a classroom polymers that break down the
Institute of Bioengineering studying survival, superbugs bacteria cell membrane, you
and Nanotechnology (IBN), would be top students, she says. worry that a lot of endotoxins will
published a paper that could Yang, who is also interested be released from the bacteria cells,
signal a break in the spiraling in using nanotechnology for and those endotoxins may cause
battle between antibiotics drug delivery, seeks and attracts sepsis.” In other words, they could
and superbugs. It looks at the interesting collaborators. The be toxic. This was exactly what
properties of an infection- development of the most recent stopped Yang from proceeding
fighting synthetic polymer, the polymer began with multinational with drug trials for a polymer she
most eye-catching element of tech company IBM. While at a published about in 2011 in Nature
Harmful strains of
which is that the polymer doesn’t conference in Australia in 2007, Chemistry. In large quantities,
Escherichia coli bacteria appear to set off an adaptive Yang heard IBM’s James Hedrick endotoxins – toxins present in
can cause infections response in bacteria at all. talk about a unique, positively the membranes of many types
that lead to abdominal
cramps, bloody diarrhea
In their study, Yang and her charged synthetic polymer his of Gram-negative bacteria – can
and vomiting. E. coli team showed that the polymer team had accidentally made cause severe diarrhea, septic
is commonly found in is biodegradable, non-toxic while working on creating shock, and even death. Smaller
the large intestines of
and can kill the Acinetobacter silicon wafers for computer amounts may cause fever, chills,
© MedicalRF.com/Getty Images
cell surfaces, moving through In the first stage of testing With imipenem Yang next looked to
‘‘STT-MRAM
is the leading
A voltage sensing scheme fast, high-density, low-power
candidate
developed by researchers alternative to existing charge-
from Singapore could based memories.
for future
improve the accuracy of “STT-MRAM is the non-volatile,
reading data from spin- leading candidate for future universal memory
based memory systems with non-volatile, universal technology.’’
only minimal modifications. memory technology,” says
The scheme responds Trinh. “It could serve in The team’s simulations
dynamically to voltage changes consumer devices, corporate suggest that their dynamic
in the system, so that it can data centers, and even high- reference scheme could be
better discern whether it is end critical applications such incorporated into existing STT-
reading a binary on (1) or as unmanned vehicles, aircraft, MRAM systems with minimal
off (0) state. and military.” modifications, and would
The cutting-edge data In STT-MRAM systems, reduce read errors by two orders
storage technology, called data bits are stored as either of magnitude.
spin-transfer torque magnetic 1s or 0s by flipping the “We look forward to
random-access memory orientation of magnetized exploiting the synergy between
(STT-MRAM), encodes data ‘bitcells’. To read a bitcell, our dynamic reference scheme
using the intrinsic angular the system compares its own and existing circuits,” says
© RICHARD KAIL/Science Photo Library/Getty
momentum of electrons reference voltage to the ‘bitline’ Trinh. “We are also working
— their spin, instead of voltage across the bitcell — the on solutions to reduce the
their charge. Quang-Kien 1 or 0 state is then identified energy consumption and
Trinh, Sergio Ruocco from based on the difference between design complexity.”
the A*STAR Data Storage the two voltages, called the
Institute and Massimo Alioto read margin. 1. Trinh, Q.-K., Ruocco, S. &
© xxxxxxxxxxxxxx
A high-fat diet could aggravate symptoms than the mice on the suggested that it was in fact
skin diseases such as psoriasis normal diet. the high-fat diet, and not the
OBESITY
by increasing the level of To understand this, the resulting obesity, that was
inflammatory cytokines in team took a closer look at contributing to higher levels of
the skin, an A*STAR-led what was happening to the skin inflammation.
study finds. immune cells in the skin of the While most people know
Previous research has obese mice. They discovered that a high-fat diet is associated
suggested that obesity is that the cells lining the blood with heart disease and diabetes,
HIGH-FAT a trigger for psoriasis, a vessels in the skin were putting not many would think about its
DIET LINKED disease characterized by
scaly, itches patches on the
out chemical signals that
caused an increase in a type
potential to cause skin disease,
says Satoshi Nakamizo, from
TO SKIN skin, thought to be associated of immune cell called a T cell. the Singapore Immunology
CONDITIONS with the immune system. So
researchers from A*STAR, and
This T cell produced another
chemical messenger called
Network and Institute of
Medical Biology at A*STAR.
A high-fat diet may colleagues in Japan, set out to IL-17, which is associated with “A high-fat diet acts on a
explore the cause underlying increased inflammation. large blood vessel such as the
worsen inflammatory the link between obesity But the researchers heart, causing arteriosclerosis,
skin conditions and psoriasis. still weren’t sure whether but it also acts on small
such as psoriasis Their study compared it was the obesity itself, or blood vessels of the skin and
obese mice which had been the high-fat diet that was causes skin inflammation,”
fed a high-fat diet and lean responsible for the immune Nakamizo says. “Diet and
mice on a normal diet. Both changes in the mice’s weight management are
groups of mice were treated skin. To answer this, they important not only for systemic
with a drug called imiquimod repeated the treatment on diseases but also for preventing
that can induce a psoriasis-like mice that were genetically skin diseases.”
skin condition. engineered to be obese even
After five days of without the input of a high- 1. Nakamizo, S. Honda, T. Adachi, A.
Nagatake, T. Kunisawa, J. et al.
imiquimod treatment, they fat diet. They found that
High fat diet exacerbates murine
noticed that the obese mice these mice responded to the
psoriatic dermatitis by increasing
that had been fed the high-fat imiquimod treatment in a the number of IL-17-producing
diet exhibited significantly manner similar to that of γδ T cells. Scientific Reports 7,
greater psoriasis-like lean, normal diet mice, which 14076 (2017).
A high-fat
diet makes
inflammatory
skin disease
© 2018 A*STAR Institute of Medical Biology
worse in mice.
CANCER
THE STOMACH’S
‘CHIEF’ SOURCE OF
STEM CELLS The study
revealed that
Stem cell reserves found Lgr5-expressing
chief cells in the
in the stomach have corpus glands
implications for the genesis can become
gastric cancer
of gastric cancer precursors.
A team of researchers at where these stem cells reside In addition, the team helping to clarify the
A*STAR has found that — at the bottom of small has implicated these ongoing debate.”
certain cells in the stomach, pits in the stomach known cells in the genesis of In the future, the
called chief cells, become as corpus glands. They gastric cancer — the fourth team intends to explore
stem cells in response to discovered in a mouse model leading cause of cancer exactly what causes
injury, providing a source of that certain cells in this globally, according to the the cells to become stem
new cells1. As well as being World Health Organization. cells. “We are interested
significant for understanding They discovered that in better understanding
Reprinted by permission from Ref. 1 © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
how the stomach lining ‘‘The theory that when these cells undergo the mechanism
renews itself, the finding chief cells can a mutation, they become responsible for converting
sheds light on how gastric be activated a major source of tumors the normally quiescent,
cancer can begin. to serve as the at the base of the corpus differentiated chief
The stomach wall is a precursor to glands (see image above). cells into proliferative,
hostile place for cells, as they gastric cancer “The theory that multipotent stem cells,”
are constantly subjected under damage chief cells can be activated says Barker. He notes
to mechanical stress and conditions is to serve as the precursor that the same mechanism
high acidity and must be to gastric cancer under could be at play when the
controversial.’’
continually replaced. The damage conditions is cells become cancerous.
most likely source of such controversial,” says “We hope that these
reinforcements is adult stem location express the gene Barker. “Indeed, a recent findings will contribute
cells, but identifying these Lgr5, a marker of stem cells study concluded that to translatable clinical
cells has been challenging. in various organs, including other cells are the true outcomes,” he adds.
“The identity of the the intestine and skin. The precursors of cancer,
gastric stem cells has been researchers also found not chief cells. In this 1. Leushacke, M., Tan, S.
H., Wong, A., Swathi, Y.,
contentious,” says Nick that these cells are not study, we conclusively Hajamohideen, A. et al.
Barker of the A*STAR normally stem cells; rather, identified Lgr5+ cells as Lgr5-expressing chief cells
Institute of Medical Biology. they become stem cells in a source of spasmolytic drive epithelial regeneration
and cancer in the oxyntic
Now, Barker and response to damage to the polypeptide-expressing stomach. Nature Cell Biology
his co-workers have located stomach wall. metaplasia (SPEM), 19, 774−786 (2017).
in the peritoneal cavity that lies liver’s tissue that protects it from
NEWLY IDENTIFIED between the abdominal wall bacteria circulating in the blood.
CELLS IN LIVER and the membrane covering
abdominal organs.
The combination of molecules on
their surface distinguished them
PROTECTION ROLE Researchers had observed from other types of immune
immune cells in the liver’s cells, including Kupffer cells.
A subset of immune capsule almost 30 years ago, When the team analyzed the
cells in the liver shields it but had not agreed on what cells’ gene expression, they found
from bacteria in the gut type they were. Scientists from it similar to — and so classified
A*STAR’s Singapore Immunology them as — macrophages, a type
Network, in collaboration with of white blood cell that engulfs
NATURE
These newly identified cells industries. Conventional and human bones.”
have branches, or dendrites, manufacturing techniques The researchers
that extend toward bacteria and INSPIRES like casting and machining, determined the principal lines
LIGHT,
other foreign substances. They however, limit the designs of stress, called isostatic lines,
are also involved in recruiting that can be fabricated as they in the lattice using a method
another type of immune ROBUST are prone to inaccuracies that combines topology
LATTICE
cell, neutrophils, to the liver. and struggle to achieve the and size optimization. This
Neutrophils crawl along the liver best results. approach allows the size,
capsular macrophages’ dendrites
to reach the liver capsule and
STRUCTURES Now, scientists at
A*STAR have invented a
shape and orientation of
each cell in the structure
provide additional immune New technique for method that uses additive to be tailored, significantly
protection against infection. creating lightweight manufacturing techniques reducing the stress between
“This study represents how to create lightweight neighboring lattice cells.
two-photon microscopy can
materials that are stiffer lattice structures with The researchers compared
contribute to the discovery and stronger than greatly improved stiffness the performance of their
of new immune cell subsets,” previously possible and strength1, paving the graded lattice structure with
says A*STAR immunologist way for new materials a uniform lattice core and
Lai Guan Ng, one of the for use in a wide range of found that their optimized
study’s co-authors. “Our study applications including impact design had increased stiffness
discovered that liver capsular absorbent materials and by 172 per cent and strength
macrophages serve as sensors sandwich structures. by 100 per cent.
for peritoneal bacteria and The design and “Our technique
recruit neutrophils to fight optimization of lightweight can create lightweight,
infection. This study shows cellular and lattice structures functionally graded lattices
that the liver has two separate is an emerging field made that greatly improve the
and non-overlapping niches possible by advances in stiffness and strength of
occupied by distinct resident metal and polymer additive additively manufactured
macrophage populations: manufacturing, such as the sandwich structures without
Kupffer cells in the liver for ability to accurately print increasing their mass,” says
mediating protection against highly complex geometries. Daynes. “These structures
systemic bacterial infection, By mimicking structures are particularly well suited
and liver capsular macrophages occurring in nature, Stephen to additive manufacturing
for protection against Daynes and colleagues processes since they are
Reproduced, with permission, from Ref. 1 © 2017 Elsevier
CELLS
GLARING LESSONS
ON SKIN AGING
A protein can be used to
measure the aging effect of
sun exposure on skin cells
Dreesen, from the A*STAR UVB light daily for ten days. to measure sun damage of skin pathological and cosmetic
Institute of Medical Biology. “In our experiment, UVB light cells, lamin B1 levels could also changes that occur in aging
Researchers decided to use only affected the epidermis, the help in the study of age-related skin,” Dreesen says.
this knowledge to look at the top layer of the skin, and it didn’t skin problems such as actinic
effects of ultraviolet light on skin seem to affect the dermis, which is keratosis, which is caused by 1. Wang, A. S. Ong, P. F. Chojnowski,
A. Clavel, C. Dreesen, O. Loss
cell aging. To begin with, they the lower part,” Dreesen says. sun exposure. It could also help
of lamin B1 is a biomarker to
exposed human skin cells in a The researchers also explore the impact of other quantify cellular senescence in
petri dish to the same amount noticed that once the mice’s environmental conditions, such photoaged skin. Scientific Reports 7,
of ultraviolet B light that might skin recovered from the as pollution, on skin aging. 15678 (2017).
MEASUREMENTS
LASER
SPECTROSCOPY THROUGH
ENTANGLEMENT
The extremely short relaxation times of
atoms can be measured by using quantum-
entangled photons
© Stockbyte/Getty
ConsensusDriver is
a new computational
method that integrates
the results from
multiple analyses to
improve prediction of
cancer drivers.
consistently outperformed
the individual methods. In BUILDING A BETTER
addition, ConsensusDriver can
determine whether unfamiliar
CHEMISTRY ION CHANNEL
mutations are cancer drivers. A synthetic channel with a strong preference
“Most groups approach
for potassium ions offers rapid transport
the question from a basic
cancer biology perspective through an artificial membrane
of finding key cancer genes.
Our interest has always been
to go beyond this and see Artificial ion channels developed developed to mimic and based ‘tail’. These molecules
how far we can move towards by A*STAR researchers could eventually surpass the functions can self-assemble so that the
personalized medicine,” says pave the way for new kinds exhibited by naturally-occurring crown ether rings line up to
Nagarajan. “If methods like of antibacterial agents and protein channels.” However, it form a tube, which acts as an
ConsensusDriver were used for biomedical sensors1. has been difficult to develop ion channel.
precision oncology, it would Ion channels are biochemical artificial channels that have a The researchers created
double the number of patients superhighways that enable ions strong selectivity for potassium a library of molecules using
for whom we would be able of metals such as potassium and over sodium ions. various amino acids, different
to recommend treatments,” sodium to zoom in and out of Zeng and colleagues have lengths of alkyl chains, and
though he adds that precision cells. Crucially, the channels are now developed ion channels crown ethers that contained
oncology remains a distant typically very selective, allowing that offer rapid potassium ion five or six oxygen atoms. Then
goal requiring extensive only one type of ion through transport with a selectivity that they formed membranes from
clinical validation. and barring others. For example, is among the highest reported the stacked channels, and tested
The team has made the naturally-occurring KcsA for any artificial ion channel. their ion transport properties.
their research tools freely potassium ion channel can The channel is formed from a The most selective channel
available online, providing transport 100 million ions per series of identical molecules they studied contained a crown
the community with a second, and only lets one sodium that stack on one another. ether with five oxygen atoms,
convenient toolbox to run the ion through for every 10,000 Each molecule contains three a phenylalanine amino acid,
18 predictions methods as potassium ions. components. At one end is a and an alkyl chain containing
well as ConsensusDriver. With “But protein-based ion crown ether, a large ring of eight carbon atoms. This could
improved predictions from channels are costly and carbon and oxygen atoms; in the transport 30 million ions per
consensus-based methods, difficult to manipulate,” says middle is an amino acid, which second, and was about ten times
researchers may be able to find Huaqiang Zeng at the A*STAR contains chemical groups that more selective for potassium ion
new drug targets by identifying Institute of Bioengineering and allow the molecules to stack in than sodium ions. This offers a
genes which are frequently Nanotechnology. “Synthetic a specific pattern; and at the much better performance than
drivers across different versions are therefore being other end is a long, carbon- previous artificial potassium ion
Reprinted with permission from Ref. 1. Copyright (2017) American Chemical Society
CANCER
TREATMENT
PHOTOTHERMAL
THERAPY BLOOMS
Flower-shaped gold
nanocrystals are too hot
to handle for tumor cells
Gold nanocrystals
grown in star
fruit juice formed
flower-shaped
structures.
100nm
Gold nanoflowers grown in chemicals called capping agents all the time in tropical infrared laser light was shone on
starfruit juice are promising can be added to direct the areas, and because starfruit cells mixed with nanoflowers, 30
agents for photothermal crystals’ growth. is rich in vitamin C, which seconds of illumination killed
cancer therapy. When injected “Capping agents will serves as the reducing every cell within the laser spot. In
into a tumor and irradiated attach to different facets agent, and polyphenolic tests with mice, photothermally-
with near-infrared laser of the nanocrystal nuclei,” antioxidants,” says Ye. As treated animals’ tumors gradually
light, the nanoflowers heat says Ye. “They regulate the the team had predicted, the disappeared — whereas in
up and kill the cancer cells crystal’s growth and stabilize vitamin C initiated and animals given either laser
around them. the final nanocrystals.” directed nanocrystal growth, irradiation only, or nanoflower
Although photothermal However, conventional capping and the polyphenolic injection alone, the tumor
therapy is an established agents are not biocompatible, compounds acted as continued its rapid growth.
idea, the agents developed so they need to be eliminated capping agents, coating the The team now plans
so far have had drawbacks, before the nanocrystals are to take the research in two
explains Enyi Ye from the used for therapy. Removal, ‘‘We will directions, says Ye. “We
A*STAR Institute of Materials however, can be difficult and will continue to develop Reprinted from Ref. 1 with permission of The Royal Society of Chemistry
continue to
Research and Engineering, may damage the nanocrystal’s develop green green methods to prepare
who co-led the current work. shape, impairing its multifunctional nanocrystals.
methods
The challenge is to achieve light absorption. We would also like to
high efficacy, stability and Ye and his colleagues tried
to prepare further exploit the practical
biocompatibility in the same an alternative ‘green’ approach,
multifunctional applications of the gold
nanocrystal, which all relate using a natural material they nanocrystals.’’ nanoflowers in areas such as
to the way the nanocrystals hoped would contain the wound healing and bacterial
are grown. biological equivalent of capping flower-shaped nanocrystals infection control,” he says.
A nanomaterial’s shape agents. This would negate the with a stabilizing,
1. Yang, D.-P., Liu, X., Teng, C. P., Owh, C.,
dictates its light capturing need to remove the compounds biocompatible surface.
Win, K. Y. et al. Unexpected
ability. During the synthesis of before nanocrystal injection into The gold nanoflowers showed formation of gold nanoflowers
nanocrystals, when gold ions the patient. strong near-infrared light by a green synthesis method as
agents for a safe and effective
are mixed with a reducing agent “I selected starfruit absorption, and were non-toxic to photothermal therapy. Nanoscale 9,
to precipitate crystal formation, juice because it is available cells. When 808 nanometer near- 15753–15759 (2017).
3D structured illumination
microscopy image of microtu-
bule regrowth at the nuclear
envelope following microtubule
degradation in a differentiated
myoblast cell. Microtubules are in
green, a microtubule organizing
center protein is in red, and the
outer nuclear envelope protein
Nesprin-1 is in blue.
Reprinted with permission from Ref. 1 Copyright (2017) by the American Physical Society.
to identify genes involved
in microtubule nucleation
at the nuclear envelope. An exotic state of matter that
“The only candidate they is dazzling scientists with
came up with was Nesprin-1,” its electrical properties, can
says Burke. The teams also exhibit unusual optical
decided to collaborate to solve properties, as shown in a
the mystery. theoretical study by researchers
Lee engineered cells at A*STAR.
lacking either Nesprin-1 Atomically thin materials,
or its LINC partners. such as graphene, derive some
In these cells, three of the of their properties from the
four centrosomal proteins fact that electrons are confined
remained in the cytoplasm to traveling in just two-
rather than accumulating dimensions. Similar phenomena
at the nuclear envelope. are also seen in some three-
The same mislocalization dimensional materials, in which
The upper and lower electron bands in a semimetal touch at places known as
was apparent in cells from electrons confined to the surface Dirac points.
patients with a congenital behave very differently from
muscular dystrophy caused those within the bulk — for properties from those of and predicted the strength
by a Nesprin-1 mutation. example, topological insulators, the more conventional with which incident radiation
By depleting each of whose surface electrons conduct topological insulators. induces electron transitions from
the three centrosomal electricity even though their To prove this, Li-kun Shi and the lower band to the upper
proteins individually, the bulk electrons do not. Recently, Justin Song from the A*STAR one. They found that surface
team discovered which another exciting class of Institute of High Performance absorption depends heavily on
protein was required for materials has been identified: Computing used an ‘effective the polarization of light, being
microtubule formation at the the topological semimetal. Hamiltonian’ approximation to 100 to 1,000 times stronger when
nuclear envelope. The difference in insulator show that the two-dimensional light is polarized perpendicular
In muscle cells with a and conductor electrical surface states in semimetals, — rather than parallel — to the
missing or defective copy of properties is down to the known as Fermi arcs, possess a crystal’s rotational axis. This
Nesprin-1, the nuclei clumped bandgap: a gap between the light–matter interaction much strong anisotropy offers a way
together rather than spreading ranges, or bands, of energy that stronger than that found in of optically investigating and
out. Understanding how an electron traveling through other gapless two-dimensional probing the topological surfaces
Nesprin-1 and centrosomal the material can assume. In an systems, such as graphene. states of Dirac semimetals.
proteins position the nuclei insulator, the lower band is full “Typically, the bulk “Our goal is to identify more
of muscle cells may help of electrons and the bandgap is dominates material absorption,” unconventional optics that arise
clarify the development of too large to enable a current to explains Song. “But we show that due to Fermi arcs,” says Song.
muscular dystrophies. flow. In a semimetal, the lower Dirac semimetals are unusual in “Topological semimetals could
band is also full but the lower that they possess a very optically host unusual opto-electronic
1. Gimpel, P., Lee, Y. L., Sobota, and upper bands touch at some active surface due to these behavior that goes beyond
R. M., Calvi, A., Koullourou, V.,
et al. Nesprin-1a-dependent
points, enabling the flow of a peculiar Fermi arc states.” conventional materials.”
microtubule nucleation form small current. Shi and Song analyzed a
the nuclear envelope via This lack of a full bandgap proto-typical semimetal with a 1. Shi, L.-K. & Song, J. C. W. Large
Akap450 is necessary for optical conductivity of Dirac
means that topological symmetric band structure where
nuclear positioning in muscle semimetal Fermi arc surface
cells. Current Biology 27, semimetals should theoretically the electronic bands touch at two states. Physical Review B 96,
2999–3009 (2017). exhibit very different places, known as Dirac points, 081410 (2017).
CANCER
TREATMENTS
t-SNE dimension-2
UNDERSTANDING
INDIVIDUAL
IMMUNE
RESPONSES
t-SNE dimension-1
A technique that identifies and
characterizes different immune A plot of all the different possible phenotypes of T cells without (left) vs. with (right) immune
checkpoint blockade immunotherapy. The colored dots represent T cells that are tumor
cell groups in individual neoantigen specific and colored by which tissue they were derived from: (red) tumor, (green)
patients could revolutionize dLN (draining lymphnode - the lymph-node closest to the tumor - peripheral immune tissue),
(blue) ndLN (non-draining lymphnode - peripheral immune tissue) and (orange) spleen (peripheral
cancer treatments immune tissue).
A pioneering technique at Washington University in St Newell’s team hypothesized 81 possible tumor antigens.
developed by A*STAR Louis, USA, have developed an that patients who were receptive They identified T cells
researchers can identify approach that can efficiently to effective immunotherapy specifically associated with
and profile specific groups identify and characterize would have tumor-specific T two neoantigens in spleens,
of immune cells that target neoantigen-specific CD8+ T cells with specific characteristics. tumors and lymph nodes.
cancer cells in individual cells in mice. Their technique The team’s technique combines Depending on the type of
patients. This approach could may help determine whether mass cytometry with heavy metal immunotherapy used, the
open the door to personalized a tumor will respond to staining to simultaneously screen neoantigen-specific T cells
cancer treatments. specific immunotherapies. and profile the multiplicity of such displayed different phenotypes
Cancer cells produce cells in blood and tumor samples. during treatment, whereas
many antigens that trigger ‘‘Our technique “Other approaches other T cell populations were
immune responses from could also identify require that you stimulate mostly unaffected.
the body. One group of the T cells with their specific “It’s possible we could
relevant antigens
immune cells called CD8+ antigens to identify them,” identify tumor-specific T cells
cytotoxic T cells recognize
to develop says Newell. “Instead, we used that could either be expanded
and bind to antigens attached
personalized isolated proteins from the and re-infused into patients to
to the surface of cancerous cancer vaccines.’’ antigens called peptide-MHCs boost their immune response,
cells. Often, mutations (major histocompatibility or used as biomarkers to
unique to individual patients “In theory, we might predict complex), which the T cell predict responses to any
create mutant antigens, or how someone will respond to receptors bind to. In addition given immunotherapy,” says
‘neoantigens’, which lead to certain immunotherapies by to formulating the proteins Newell. “Our technique could
© 2018 A*STAR Singapore Immunology Network
a tumor-specific immune looking at the characteristics carefully to promote stable also identify relevant tumor
response. Scientists hope to of the immune cells that are interactions, we labelled them antigens to develop personalized
harness these responses to create circulating in the patient’s with heavy metals so that cancer vaccines.”
personalized cancer treatments, blood,” explains Newell. they were detectable in high-
and possibly neoantigen-based “However, this is challenging, throughput mass cytometry.” 1. Fehlings, M., Simoni, Y., Penny,
H. L., Becht, E., Loh, C. Y. et al.
cancer vaccines. because there are huge In experiments on mice Checkpoint blockade therapy
Now, Evan Newell and numbers of circulating cells with sarcoma tumors that reshapes the high-dimensional
co-workers at A*STAR’s and only a tiny proportion of responded well to particular phenotypic heterogeneity of murine
intratumoural neoantigen-specific
Singapore Immunology them are neoantigen-specific immunotherapies, the team CD8 + T cells. Nature Communications
Network, along with scientists CD8+ T cells.” analyzed T cells targeting 8, 562 (2017).
Cylindrical silicon
nanoparticles of
different sizes reflect
light across a wide
gamut of colors.
THERAPEUTICS
ENGINEERING
A SAFER
ANTIBODY DRUG
By taking advantage of the
body’s natural diversity,
antibody drugs can be made
less toxic by having a more
localized effect
An innovative approach to be undertaken,” says Samuel isotypes that may have greater IgD versions of the antibody
protein engineering could Gan, head of the Antibody and tissue precision. drugs proved inferior, both
help make antibody-based Product Development group at Their finding lays the in terms of yield and HER2-
drug therapies less toxic and the Bioinformatics Institute and groundwork for future antibody targeting, but IgE and IgA
more effective. the p53 Laboratory at A*STAR. therapies that can be safer for versions both generally retained
Working with two antibody patients without compromising the effectiveness of the original
drugs taken by thousands of yield or potency. therapies — which raises
‘‘There is a
women with breast cancer The researchers worked with the possibility of developing
whole range of
each year, A*STAR researchers trastuzumab and pertuzumab, two safer versions of trastuzumab
have shown the possibility of
possibilities to using antibody drugs marketed under and pertuzumab based on
transforming these agents — more localized the brand names Herceptin® these alternate isotypes. Most
which normally circulate in antibodies as and Perjeta®, that selectively interestingly, the findings also
© ALFRED PASIEKA/SCIENCE PHOTO LIBRARY/Getty
the bloodstream, but can also prophylactics.’’ bind to different parts of human show that constant regions in
harm healthy heart tissue — into epidermal growth factor receptor antibodies can influence in
alternative forms that may have Antibodies are also known 2 (HER2), a protein that is the antibody’s ability to bind,
more localized tissue distribution. as immunoglobulins, and they implicated in approximately 20 a finding that is often not
This tweak should result in fewer come in five main ‘isotypes’: IgA, per cent of all breast cancer cases. noticed and often neglected in
side-effects, while potentially IgD, IgE, IgG and IgM. Most They transformed these IgG antibody research.
reducing the dosage needed, therapeutic antibody drugs are of antibodies into all five human As Gan points out, both IgE
which could help lower the cost the IgG isotype that circulate in isotypes and the four subtypes, and IgA antibodies are likely
of treatment. the bloodstream, but Gan’s team and examined what impact that to be more active in the ductal
“It’s proof-of-concept that showed they could remodel IgG change had on drug production tissues of the breast, where
such antibody modification can antibodies into some of the other and binding to the HER2 target. HER2-expressing tumor cells
A SUSTAINABLE SOURCE
CANCER OF NATURAL KILLERS
Generating large numbers of universal immune
cells could transform cancer immunotherapy
A scalable method of generating cells. This can limit the use of body, including NK cells. This is
universal ‘off-the-shelf ’ natural therapies considerably,” says the first time peripheral blood
killer (NK) cells for cancer Shu Wang at the A*STAR cell-derived iPSCs have been
immunotherapies has been Institute of Bioengineering used to generate NK cells.
devised by A*STAR researchers. and Nanotechnology, who Wang’s team designed a
Their technique could ensure led the study. “We wanted new protocol to derive NK cells
that future NK cell-based cancer to devise a new method of from iPSCs, with a focus on
treatments can be used for generating large numbers of robustness and scalability. They
most patients. pure, universally-suitable NK co-cultured iPSCs with bone
NK cells are a group of cells that could widen the use of marrow connective tissue cells
small white blood cells from such immunotherapies.” — these activate the signaling
the innate immune system that processes needed for cell
help kill virus-infected cells differentiation and commitment
‘‘We may now
and malignant cancer cells. to a specific cell type, which
Scientists can harvest NK cells
have an invaluable resulted in large yields of
Changing the
isotype of and use them to directly target
cell source for NK cells.
Immunoglobulin cancer cells. However, existing a wider group “An unexpected bonus of
can make it easier
techniques generate limited of patients.’’ our protocol was that most
to target specific
parts of the body. numbers of NK cells from derived NK cells were free of a
selected donors that are suitable The team needed a readily particular group of inhibitory
for specific patients only. available, sustainable and non- receptor proteins that can
“Current donor-dependent controversial source of stem limit universal application in
are also found, and they could NK cell harvesting methods cells from which they could patients,” says Jieming Zeng, the
be combined with low doses of carry the risk of graft-versus- derive massive numbers of NK first author of the study. “This
blood-targeting IgG antibodies host disease, because traces cells. So they used peripheral means that we may now have
to guard against circulating of other cells and molecules blood cells to generate induced an invaluable cell source for a
metastatic cells while lowering from donors that are mixed human pluripotent stem cells, wider group of patients.”
the risk of other side-effects such in with the NK cells can iPSCs, which can differentiate Scaling up the manufacture
as cardiac toxicity. react to patients’ normal into every type of cell in the of NK cells will require
Additionally, Gan suggests considerable further investment,
that immunotherapies could particularly with its reliance
be developed with IgA and on the connective tissue cell
© 2018 A*STAR Institute of Bioengineering and Nanotechnology
Reprinted with permission from Ref. 1. Copyright (2017) American Chemical Society
Carving shapes into Defect states on the nanocrystal
~6nm
semiconductor surfaces smaller surfaces were pinpointed as the
than 10 nanometers is a particular cause of the new optical behavior.
expertise of M. S. M. Saifullah “The nice thing about
6nm
from the A*STAR Institute photoluminescent ZnS
6nm of Materials Research and nanocrystals is they can be
Engineering, and colleagues. They arranged into practically any
direct high-powered electron shape,” says Saifullah. “In
beams on to special thin films the future, we would like to
called ‘resists’. Areas of the resist combine these nanostructures
exposed to the focused beams with plasmonics.”
7nm undergo chemical changes that
enable tiny features to stay in place 1. Lu, X., Denver, D., Chandar, J., Chen, Y. &
Lou, J. An overlapping domain decom-
50nm while the surrounding film is
position based near-far field coupling
washed away by solvents. method for wave structure interaction
Light-emitting ZnS nanostructures can be patterned into nearly any shape, In most electron-beam simulations. Coastal Engineering 126,
including grids as above, using a multipurpose photoresist. lithography techniques, the 37–50 (2017).
Relocation of N-acetylga-
lactosaminyltransferases
from the Golgi apparatus to
the endoplasmic reticulum
makes cancer cells more
invasive. (above) Illustration
of cancer cells breaking
through tissue.
“yet it is involved in virtually active at the ER in liver tumor 1. Nguyen, A. T., Chia, J., Ros, M.,
Hui, K. M., Saltel, F. et al. Organelle
every aspect of human biology cells from mice and humans,
specific O-glycosylation drives
and it has long been known rather than being active at the MMP14 activation, tumor growth,
that glycosylation is altered Golgi apparatus as they are and metastasis. Cancer Cell 32,
in cancer.” in healthy cells. Furthermore, 639–653.e6 (2017).
CANCER
RESEARCH
A BLOOD TEST
FOR CANCER
RECURRENCE
A greater understanding
Assay for genetic quirk can provide of biomarkers will yield
a wealth of information on patient more accessible ways
to screen, monitor, and
disease status and prognosis treat conditions such as
breast cancer.
Despite great advances in and surgery, these cells can allows clinicians to inform in discussions to start a clinical
medicine, cancer remains survive, regrow, and cause patients of the increased risk trial with the drug pacritinib,
a death sentence for many. recurrence,” says Goh. The team, of breast cancer recurrence, as using our biomarker to guide
“Patients are still dying from led by A*STAR’s Qiang Yu, found well as monitor the progress of treatment,” explains Goh.
breast cancer relapse,” says Jian that TICs possess an abnormally treatment and the emergence “Pacritinib is not yet approved
Yuan Goh, of A*STAR’s Genome high number of copies of a of tumor resistance to therapy, for use in breast cancer, so we
Institute of Singapore. The specific section of DNA. This based on the changing levels of first need to see whether tumors
researcher and his colleagues, ‘copy number amplification’ the biomarker. The researchers respond to this treatment.”
a team from Singapore, China, results in an overproduction of also found the amplification to be “What we’re trying to
the United States, and Denmark, the proteins coded for by that correlated to cancer metastasis. do is provide a cost-effective
have recently identified section of genetic material. TIC presence might signal way for clinicians to track
a genetic aberration in a a bleak prognosis for patients breast cancer recurrence. The
particularly aggressive subtype if it didn’t also offer a unique alternative — genetic sequencing
‘‘What we’re trying
of breast cancer cells that, when avenue of treatment. With an — is comprehensive, but very
quantified, can provide insights
to do is provide a abnormally high number of expensive. You can’t imagine a
into a patient’s cancer status,
cost-effective way a specific set of genes, TICs patient coming in every month
chances of relapse, and treatment for clinicians to overproduce the S100A family to be sequenced for 3,000
progress. This discovery paves track breast cancer of proteins. As these proteins dollars, but, if we develop this
the way for an alternative recurrence.’’ provide TICs with their assay, testing will be a lot more
to invasive and expensive chemo-resistant properties, affordable,” says Goh.
biopsy testing. Goh and his colleagues have the researchers are now
© Image Source/Getty
One model of cancer’s produced a ‘liquid biopsy’ assay investigating pharmacological 1. Goh, J. Y., Feng, M., Wang, W., Oguz, G.,
Yatim, S. M. J. M. et al. Chromosome
proliferation involves the that detects this genetic quirk interventions that might block
1q21.3 amplification is a trackable
presence of chemotherapy- within circulating fragments of this pathway and provide a biomarker and actionable target for
resistant tumor-initiating cells tumor DNA found in blood. A lifeline in otherwise incurable breast cancer recurrence. Nature
(TICs). “Even after chemotherapy presence of TIC-linked DNA cases of breast cancer. “We’re Medicine 23, 1319–1330 (2017).
© Sophie Laidlaw/EyeEm/Getty
IN SMALLER PACKAGES
UV rays, helping to protect care products is limited by
the plant’s more delicate two key factors, explains
cellulose structures from Balamurugan Ramalingam
Adapted polymer offers sun damage. Researchers at from the A*STAR
plant-based protection from A*STAR have found a way Institute of Chemical and
the Sun’s harmful rays to make short-chain lignin- Engineering Sciences,
like structures that retain who led the current work.
the parent molecule’s UV High molecular weight
natural lignin polymers
are inherently insoluble in
common solvents, and disperse
poorly into mixtures of other
materials, making it difficult to
work with.
‘‘We were
particularly
pleased by the
broader UV
blocking ability
and higher molar
absorptivity
exhibited by the
oligomers.’’
Reprinted from Ref 1. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
component small molecule
monomers to improve
workability, but this
removes natural lignin’s
UV-absorbing characteristics.
Ramalingam and his
coworkers suspected that the
sweet spot for making UV
blockers might be to form
lignin-like ‘oligomers’, short-
chain structures rather than
the long-chain polymers of
natural lignin.
The team showed they
could form lignin-like
A lignin-like short chain oligomer (right) absorbs UV light far more effectively than its component monomers (left). oligomers either by chemically
or penetrate the skin when just a few femtoseconds — one A*STAR’s Singapore Institute or slower than the speed of
used in sunscreens. quadrillionth of a second — to of Manufacturing Technology light, and even backwards,”
“We are currently excite atoms and molecules and (SIMTech). “However, it says Wong.
evaluating the possibility observe how they respond. is notoriously challenging
of incorporating lignin- One of the methods used to obtain exact analytical 1. Wong, L. J. & Kaminer, I.
Ultrashort tilted-pulse-
like oligomers into commercial to enhance the interaction solutions for realistic pulses.”
front pulses and nonparaxial
sunscreens, towards between a laser pulse and the Wong and collaborator, tilted‑phase‑front beams. ACS
developing nature-inspired target atom or molecule is to Ido Kaminer, from MIT Photonics 4, 2257−2264 (2017).
personal care products,”
Ramalingam says. 1
10
1. Lim, J., Sana, B., Krishnan, R.,
Seayad, J., Ghadessy, F. J. et al.
Laccase-catalyzed synthesis 0 0 A progression
of low-molecular-weight lignin-
of femtosecond
like oligomers and their application
-10 tilted-pulse-
as UV-blocking materials.
front pulses.
Chemistry — An Asian Journal 13, -1
284 (2018). -20 -10 0 -10 -20
A*STAR researchers
have developed an
RNA-based anticancer
therapy that targets a
metabolic pathway in
tumor-initiating cells.
Dave Wee from the Institute of synthetic RNA sequences decarboxylase transcripts as an
High Performance Computing. (steric hindrance antisense anticancer therapeutic strategy
for non-small-cell lung carcinoma.
Targeting TIC metabolism is oligonucleotides, or shAONs) Molecular Therapy Nucleic Acids 9,
emerging as a promising strategy that supressed the production of 263-273 (2017).
MUTATION
that task.
This strategy helps correct
for brain differences between LINKED TO RARE
SKIN DISEASE
individuals, and avoids the
hassle of multiple preparative
sessions. However, it doesn’t
account for the fact that Impaired melanin production
individuals themselves can differ underlies an inherited A patient with hypo- and hyper-pigmented macules (white and black
in their brain activity associated pigmentation disorder arrowheads, respectively) and atopic eczema (open arrowhead).
with a motor imagery exercise
from one rehab appointment to
the next.
It is this gap that is filled by A genetic mutation that affects that their form of the disease colleagues identified a mutation
the newest adaptive strategy. the production of the skin requires two copies of the in a different region of the
It works much the same as pigment melanin is associated altered gene and thus, ENPP1 protein. As Reversade
the machine-learning model, with a previously unknown follows a recessive pattern explains: “We found a mutation
but it doesn’t stop at just one form of Cole disease — a rare of inheritance. that affects the SMB1 domain
calibration session. It keeps condition characterized by The team found that of ENPP1 and interferes with
updating its model of how the unusually light-colored and the eight patients had a the protein’s ability to pair
patient’s EEG patterns match dark-colored skin areas as well common mutation in the with itself ”.
motor imagery exercises as as spots of thickened skin on gene encoding ectonucleotide Further examination
new information comes in after the palms of the hands and the pyrophosphatase/ of the skin from a patient
each and every session, thereby soles of the feet. phosphodiesterase 1 (ENPP1), and their unaffected sibling
correcting for day-to-day A team led by Bruno a protein that regulates the revealed that in the patient’s
changes in neural connectivity. Reversade at the A*STAR production of extracellular skin there was an upregulation
Ang and Guan have Institute of Medical Biology inorganic pyrophosphate (PPi). of melanin production in the
retrospectively applied the analyzed the DNA of eight PPi prevents the accumulation darker skin regions and a
adaptive model to the clinical patients from three unrelated of calcium in the body and has downregulation in the lighter
data from their earlier trial. families in Sousse, Tunisia, a key role in bone development colored areas compared with
As they report in their new presenting the clinical features and the formation of abnormal normal skin, indicating that
paper, this would have of Cole disease. All patients calcium deposits in soft tissues, the SMB1 mutation impairs
significantly improved motor developed the symptoms including skin. melanin production.
imagery detection in the within the first three months Interestingly, the identified “The association of
Reprinted from Ref. 1, Copyright 2017, with permission from Elsevier
patients. The researchers of life and went on to mutation differs from others different ENPP1 mutations
have also tested the adaptive develop eczema. in the same gene that have with Cole disease suggests that
strategy on 11 additional Until now Cole disease been associated with the there is a spectrum of skin
stroke patients in another has been reported to follow dominant form of Cole pigmentation anomalies that
clinical trial last year. “We are a dominant pattern of disease. Previous studies share some clinical features,
now analyzing the results and inheritance, which means have shown that mutations but have different patterns
will be reporting the findings one copy of an altered affecting the SMB2 domain of inheritance and severity”
soon,” Ang says. gene in each cell is enough of ENPP1 protein disrupt the Reversade concludes.
to cause pigmentation transport of melanin from the
1. Chourabi, M., Liew, M. S., Lim, S.,
1. Ang, K. K. & Guan, C. EEG-based abnormalities. However, cells in which it is produced
strategies to detect motor imagery H’mida-Ben Brahim, D. &
parents and siblings of (melanocytes) to epidermal Boussofara, L. et al. ENPP1
for control and rehabilitation. IEEE
Transactions on Neural Systems
these eight patients carrying cells in response to insulin. mutation causes recessive Cole
disease by altering melanogen-
and Rehabilitation Engineering 25, one copy of an altered gene With the help of L’Oréal esis. The Journal of Investigative
392–401 (2017). were unaffected, indicating Research, Reversade and Dermatology 138, 291–300 (2018).
Interacting proteins
have similar protein
solubility across
different denaturing
temperatures.
TURNING UP THE
disrupted in disease states. increasing temperature causes
An international study led them to precipitate out of solution.
HEAT ON PROTEIN by Chris Soon Heng Tan at the Thermal proximity coaggregation
INTERACTIONS
A*STAR Institute of Molecular (TPCA) is based on the idea that
and Cell Biology describes a new proteins that are part of a stable
technique that uses powerful protein complex will coprecipitate,
Deep data analytics drive the data analytics to infer protein- by virtue of close proximity, and
© Brandy Arivett/EyeEm/Getty
development of a technique that protein interaction dynamics have a similar precipitation profile
sheds light on drug action by from the melting behavior of across different temperatures (or
protein complexes inside cells1. melting curve).
monitoring the dynamics of thousands
Methods to capture In isolation, different
of protein complexes simultaneously snapshots of protein-protein proteins are likely to have
within intact cells interaction networks in cells different melting curves, but
CANCER
BIOLOGY
THE MOLECULAR
PATH TO
BETTER ORAL
CANCER CARE
A better understanding of
how genetics influences
responses to mouth
cancer drugs could lead to
improved treatment
characterized by the worked well in two the G/G genotype cells to increased significantly.
uncontrolled growth of patients with two copies of become G/A at the same They also found
thin, scale-like squamous the EGFR coding gene with location increased their that the tumors of seven
cells in the outer layer of an adenine (A) nucleobase sensitivity to the drugs patients with the A/A
the mouth. Only around in place of the more 70-fold. “We were pretty genotype shrank following
50 per cent of patients who common guanine (G) at a surprised it had such a treatment with EGFR-
are treated through surgery particular location. dramatic effect,” says Iyer. inhibiting drugs.
or radiotherapy are cured, More recently, tests by The genetic mutation While the mechanism
and the average duration Gopal Iyer, also at NCCS, occurs in a section of DNA underlying this effect is not
of survival of those with and Tan showed that OSCC that modulates the stability fully understood, the group
that could provide for and it is typically supported on by mixing particles of nickel catalyst stabilized in porous SiO 2
matrix for substituted natural gas
improved targeting of another material such as alumina hydroxide with tetraethyl production. Catalysis Today 299,
existing treatments. or silica. But the catalyst can orthosilicate. After further 193–200 (2018).
Transmission electron microscopy images of (left, center) nickel-silica catalyst and (right) a commercial catalyst.
© aaaaimages/Moment/Getty; ©KATERYNA KON/SCIENCE PHOTO LIBRARY/Getty; Reproduced from Scientific Reports 7, 16599 (2017) and
licensed under CC-BY-4.0 (https://creativecommons.org/licenses/by/4.0) © T. Hirata et al.; © 2018 A*STAR Institute for Infocomm Research
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