KERNEL Issue 3, 2021 CAN A COMPUTER THINK - IISc
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Research Newsletter of
the Indian Institute of Science Issue 3, 2021
KERNEL
Editorial
CAN A COMPUTER THINK
LIKE A BRAIN?
Building devices that mimic
the human brain is the ‘holy
grail’ of computing. In this
issue of Kernel, learn more
about how IISc researchers
are working on developing
brain-inspired systems that
can lead to smarter and
faster computers.
This issue also spotlights
research on a key protein
An integrated chip designed at the NeurRonICS lab to implement a neuromorphic circuit for edge computing (Photo: NeuRonICS lab)
that helps HIV fuse with the INSPIRED BY THE HUMAN BRAIN, RESEARCHERS AT IISc AND ELSEWHERE
host cell, and hitchhiking ARE TRYING TO MAKE SMARTER AND FASTER COMPUTING DEVICES
worms that live in fig trees.
Consider a child playing on a swing, one of these tasks. Our brains clearly
while licking on a candy, waving to her outsmart computers. Heck, even chicken
We also feature the work mom, and joining the other kids in a brains outsmart our best computers.
of an IISc researcher who song from their favourite cartoon show. The realisation of such limits has led to
It may not seem extraordinary, but look the rise of ‘neuromorphic’ computing. At
is working towards the
closely and you will see that a four-year its core lies inspiration from biological
ambitious goal of making old is carrying out complex coordinated systems because the “nervous system
biology more predictive. body movements, visual search, social is the most sophisticated system that
engagement and memory recall, all at engineers can learn from, which is …
the same time. The best of our robots, in developed over billions of years of
contrast, can only do a half-decent job at evolutionary process,” says Chetan
Continued on page 2
Neurons growing on the multi-electrode array. Black dots are electrodes that pick up signals from neurons and carry to trace pads for recording (Photo: Grace Mathew Abraham)
Continued from page 1
Singh Thakur, Assistant Professor at can act as an efficient pre-processing the network did not go into overdrive,
IISc’s Department of Electronic Systems unit for speech-based machine learning and remained stable – a condition called
Engineering (DESE). The features that make applications (FPGA or Field-programmable global homeostasis. This work might lead
our brains super-efficient, he explains, are gate array is an integrated circuit that can to better understanding of learning and
the ‘PPA’ – power, performance and area be programmed after manufacturing for memory, which require persistent input-
metrics – a term routinely used by circuit different applications). driven changes in neuronal networks while
designers. maintaining stability. In collaboration with
Moving up from such sensors, the lab Thakur’s lab, the group is also currently
Weighing just 1.5 kg, the human brain has also successfully modelled a network working on interfacing a neuromorphic
is compact, highly efficient and power- of grid cells and place cells – types of cochlea with a live neuronal culture to
thrifty (the calories in a banana can keep neurons that help us track where we understand how a neuronal network
it energised. Contrast that with a desktop are. This recent work is a collaboration distinguishes sound signals.
computer which uses up to 250 watts – the with Rishikesh Narayanan, Associate
equivalent of 2,000 bananas an hour). In Professor at MBU. This spatial navigation Neuromorphic computing is a young but
addition, our brains are fault-tolerant, as model could be used by robots to move rapidly growing field, with huge challenges
they can adapt to neuron loss, and are self- intelligently in novel environments. Such ahead. How one neuron can have thousands
learning. Neuromorphic engineering aims ‘biomimetic’ systems can be built on of synapses in a miniscule space is a
to marry these features, essentially etching silicon chips, another area of focus in the ‘routing’ problem yet to be solved in
brain architecture on to solid state devices. NeuRonICS lab. Towards this goal, they silicon, as denser connections can lead to
have used novel devices to model neuronal dissipated currents, wrecking the whole
Neuromorphic computing combines diverse interconnections (synapses). enterprise. Another challenging area is
disciplines – biology, electrophysiology, communication. Neurons compute on a
signal processing and circuit design, to In contrast to Thakur’s approach, gradation of inputs, but send a spike as
name a few. In 2015, such interdisciplinary Bharadwaj Amrutur, Chair of the Robert output – hence banking on both continuous
exchange at IISc led to the formation of Bosch Centre for Cyber Physical Systems and discrete signals. Neuromorphic
the Brain, Computation and Data Science and Sujit K Sikdar, Professor at MBU, have design too will have to incorporate mixed
initiative, supported by the Pratiksha been working on developing neuro-electric signal processing, to perform efficient
Trust. The group brings together labs from hybrid devices by using neurons grown communication along with computation.
DESE, Centre for Neuroscience (CNS), in the lab rather than recreating them Better neuromorphic designs can lead
Molecular Biophysics Unit (MBU), Electrical in silicon. This brain-in-a-dish approach to developing large-scale neural chips
Communication Engineering (ECE) and harnesses the parallel computing capacity to simulate brain areas, and ask “better
other departments. An interdisciplinary and power efficiency of neurons as well questions” about the brain – something
PhD programme has been launched under as the accessibility of well-developed Thakur looks forward to doing. He sees this
its umbrella, along with three Distinguished hardware and software. In an earlier study, as coming full circle with the two goals that
Chair positions. they connected input devices (sensors) to early neuromorphic researchers had – the
a live neuronal culture which was specially engineering goal of building neuro-inspired
One of the groups under this initiative is grown on metal contacts called electrodes. systems, and the scientific goal of using
the NeuRonICS lab, headed by Thakur, The electrodes conducted appropriate them to study brains. Successfully building
where research spans diverse levels. On one signals from sensors to neurons to compute a brain-like network in silicon could result
end, they work on algorithms for “event- a solution for an obstacle avoidance in a computing resource for neuroscientists,
based sensors”, which are sensory devices problem. The resulting activity of the enabling them to perform some experiments
modelled on biological systems. An example neurons was used to control a navigating without having to use animals.
of this is a neuromorphic camera, which robot seamlessly in real time. As we navigate these technical challenges,
can be more data- and power-efficient than neuromorphic computing raises new
conventional cameras. Its speedy tracking In another project, they used similar questions in the fields of science policy,
makes it useful in applications such as neuronal cultures to demonstrate law and ethics. And at the other end of such
recognising high-speed activity and detecting memory traces. They trained the network challenges is Thakur’s question: “Can we
anomalies. The lab is also developing using a “barrage of inputs” so that build something that is useful?”
algorithms for a ‘silicon cochlea’, an FPGA- specific connections developed between
based model of the cochlear system that neurons. Despite these disturbances, - Sidrat Tasawoor Kanth
KERNEL | ISSUE 3, 2021 | Pg 2
HIV-1 vesicle and human bilayer are tethered by gp41 trimer in the presence of explicit water models (pink dots) (Image: Biswajit Gorai)
MODELLING HIV FUSION
UNDERSTANDING HOW THE VIRUS FUSES WITH HOST CELLS CAN POINT SCIENTISTS TO BETTER
ANTIVIRAL STRATEGIES
An interdisciplinary team of researchers and Chair of the Department of Physics In another first, the team built models of HIV
at IISc has used robust computer and the corresponding author. and host membranes with lipid compositions
simulations to understand how the Human nearly identical to biological membranes.
Immunodeficiency Virus (HIV) – which The HIV envelope protein assembles into Using different membrane models, the
causes AIDS – fuses with the host cell a three-part structure such that each unit authors showed that only the membranes
membrane. Published in the Journal of comprises one gp41 protein. At the time with such identical lipid composition fused
Chemical Information and Modeling, the of fusion, gp41 appears to fold into a six- successfully, while the rest did not, indicating
study focuses on a process called gp41 helix bundle structure, which is thought that the lipid composition of the membranes
mediated membrane fusion. to be necessary for membrane fusion. is critical for fusion.
Maiti elaborates, “There were a lot of
Gp41, a core component of the HIV envelope hints from experimental work which The researchers also analysed the nature of
protein (Env), is essential for the viral showed that gp41 forms a six helical lipid transfer during fusion and found that
membrane to fuse with the cell membrane bundle in the post-fusion step. That the trio of gp41 units drives changes to the
of a type of immune cell in the host called prompted us to test the hypothesis that structure and arrangement of lipids at the
T cell. This step is critical for HIV to invade gp41 could actually help in fusion, which site of fusion. Finally, using mathematical
and subsequently replicate within the can eventually help virus invasion.” calculations, the team found that the
host cell. “If gp41 fusion is blocked, then presence of gp41 reduces the energy required
the whole invasion can be blocked there,” The team first built computational for fusion by about four-fold, thereby making
explains Biswajit Gorai, a former postdoc at models of HIV and host cell membranes, this process more favourable.
IISc and first author of the study. Therefore, and then simulated the fusion process.
understanding the membrane fusion process “Initially we started with millions of Currently, the team is working on identifying
may help researchers in developing effective atoms and it was very slow … but then mutations that can be introduced in gp41 to
antiviral strategies. we turned to a coarse-grained model, block the fusion step. They are also hoping
so now we can have microsecond to develop antibodies that can prevent
Although a lot is known about the simulations,” explains Gorai. Starting infection. “Together with my colleague,
molecular details of viral entry, the optimal with no gp41 on the HIV membrane as Narendra M Dixit [Professor, Department
stoichiometry – the balance of components the baseline, the authors incrementally of Chemical Engineering], we are trying to
– required for infection has remained added gp41 units to their simulation. On pursue this line of a neutralising antibody
uncertain. “We wanted to see … how many doing so, they found that at least three system,” says Maiti.
gp41 units are required to achieve this gp41 units act cooperatively and are
process,” explains Prabal K Maiti, Professor necessary for fusion. - Sukriti Kapoor
KERNEL | ISSUE 3, 2021 | Pg 3
Pollinator wasp on a fig fruit (Photo: Nikhil More)
HOW HITCHHIKING WORMS
CHOOSE THEIR VEHICLES
EVEN TINY ORGANISMS LIKE WORMS ARE CAPABLE OF MAKING COMPLEX DECISIONS, NEW STUDY FINDS
Tiny worms that live inside fig trees use to get on to an overcrowded bus unless worms selected the former.
the fig wasp as a “vehicle” to hitch rides there was no other bus available.”
from one tree to another, by crawling into Although the worms could distinguish
the wasp’s gut without harming it. This The fig tree shares a win-win relationship between wasps carrying different
relationship has existed for millions of with the fig wasp – the wasp helps in numbers of their own species,
years. But how do these worms – called pollination and the tree provides food. surprisingly, they could not recognise
nematodes – choose their wasp vehicles? The tree also hosts three different types of members of a different species, and
What cues do they use to check for co- worms. These worms rely entirely on the treated those wasps carrying them as
passengers? A new study from the Centre wasps, which ferry young worms from one empty vehicles.
for Ecological Sciences (CES) at IISc fig tree to another, where the worms then
provides some answers. mature, mate and give birth. The team also found that herbivorous and
carnivorous worms – which are different
It shows that the worms generally tend to In an earlier study, the researchers used species – used different factors to decide
choose wasps that have less crowded guts, controlled experiments to show that if on their vehicle. The herbivores preferred
and are already carrying other worms there are too many worms boarding a wasp, empty vehicles but liked to board them
of their own species. Travelling with they turn into parasites and affect not just in pairs so that they had a guaranteed
members of their own species can boost the wasp but also the tree they reach. “But mating partner when they reached their
their chances of finding a mate when they in a natural scenario, you will find that the destination. The carnivores, on the other
reach their destination. Wasps carrying nematode numbers will always be low,” hand, preferred those vehicles that
fewer worms also have a greater chance of says Satyajeet Gupta, Research Associate already carried a few members of their
reaching the destination safely. at CES and first author of the study. species.
“The main take-home message is that The new study shows that, to avoid “We’ve just scratched the surface,”
even very tiny organisms such as overcrowding, the worms do tend to select says Gupta. “This is a preliminary study
nematodes have complex decision- wasps with fewer passengers. They check towards [answering] the bigger question
making processes,” says Renee Borges, for this using chemical cues – they sniff of how nematodes really make decisions
Professor at CES and senior author of the out volatile compounds that the wasps when they are selecting a host … or a
paper published in the Journal of Animal emit by standing on their tails and waving vehicle.”
Ecology. “This kind of decision-making is their heads around. When the researchers
exactly what we humans may do when we offered the worms a choice between - Ranjini Raghunath
are making choices about which mode of compounds emitted by a wasp carrying
transport we may use. We wouldn’t want either fewer or more passengers, the
KERNEL | ISSUE 3, 2021 | Pg 4
Image: Dharma Pally
DIFFERENCES IN SUGAR LEVELS DRIVE
BREAST CANCER INVASION
Malignant tumors are increasingly higher levels of the sugar stick less recombined them. Cells with higher 2,6-
being understood as heterogenous – a strongly to their surroundings and are less Sial levels moved slowly and formed the
patchwork of cells that look and behave likely to invade through them, while those tumoroid’s central bulk, while those with
differently, and cooperate or compete with with moderate levels stick strongly and moderate levels moved fast and formed the
each other as the cancer spreads. invade more efficiently. invading front.
A recent study led by Ramray Bhat in the Using an in-house 3D culture technique, Using computer models, the team also
Department of Molecular Reproduction, the researchers reconstructed the tumor showed that having a slow-moving central
Development and Genetics shows that a microenvironment on a dish to film the bulk boosts the efficiency with which fast
specific sugar called 2,6-Sial is expressed tumoroid – cluster of cancer cells – as moving cancer cells can ‘unjam’ and spread
to different levels on the surface of it grew. Then, they separated cells with outwards in a circular fashion, thereby
different breast cancer cells. Cells with differing 2,6-Sial levels, labeled and justifying the need for heterogeneity.
Image courtesy: Vinod Ganapathy lab
ENABLING PRIVACY-COMPLIANT
DELIVERY DRONES
Delivery drones are typically equipped complex, a university campus, or a city Privaros incorporates new mechanisms
with various sensors such as cameras, municipality to ensure that “guest” into the drone software stack that
microphones, GPS, and Lidar. A malicious delivery drones visiting the airspace are allow such host-specified policies on
drone fleet service operator could misuse privacy-compliant. The host airspace board the drone. Trusted hardware
these sensors to turn delivery drones into decides what privacy policies it wishes on board can be used to prove to the
flying spies. to enforce. For example, an apartment host airspace that the guest drone is in
complex could require that all images compliance with its policies.
Researchers in the Department of of residents appearing in the video feed
Computer Science and Automation led captured by the drone be blurred out This work also shows how Privaros can
by Vinod Ganapathy have now developed before the video feed leaves the drone. be integrated with upcoming policy
“Privaros”, a set of enhancements to Or, a city municipality may require that frameworks, such as India’s Digital Sky
the drone software stack, which allows a drone only moves along certain pre- framework.
“host airspaces” such as an apartment specified drone lanes.
KERNEL | ISSUE 3, 2021 | Pg 5
Image: Aditi Jain
NANOFIBER PLATFORM TO STUDY
MUSCLE DISORDERS
Skeletal muscles are formed by the fusion is mainly because of the lack of suitable Experiments showed that the lab-grown
of parent muscle cells called myoblasts. lab-made muscle models that can replicate muscle fibers retain their alignment
These muscles are usually tethered to behaviour akin to that of skeletal muscles when grown on such polymeric
the bones by tendons. Skeletal muscle inside the body. Researchers at the Centre substrates and could reproduce critical
disorders accompany loss in muscle for BioSystems Science and Engineering, properties of skeletal muscles, such as
fibers, which often causes difficulty in Department of Materials Engineering stress-induced muscle degeneration. The
movement, pain, and stiffness upon stress and Department of Microbiology and Cell nanofiber mesh offers a robust platform
and aging. Biology have recently addressed this issue. to not only study muscle disorders, but
They used nanofibers of polycaprolactone also to test the effectiveness of drugs to
Despite extensive research in the lab, (PCL), a biodegradable polyester, to treat them.
current treatments for such disorders create a mesh-like structure on which they
are often ineffective. This gap, in taking cultured myoblasts in the lab and allowed - Debraj Manna
knowledge from the bench to the bedside, the cells to grow into muscle fibers.
Image courtesy: Sanjiv Sambandan
SELF-HEALING CIRCUITS
Flexible electronic devices such as foldable and the Department of Engineering, In flexible TFTs, silver particles of a
display screens, wearable sensors, and University of Cambridge, have specific size, embedded in insulating
self-powered, portable energy devices are collaborated to develop such circuits. silicone oil at an optimum density, were
made up of millions of circuits composed found to be ideal for healing gaps arising
of thin-film transistors (TFTs). These They packaged particles that can from electric failure or mechanical
devices are prone to open-circuit failures conduct electricity in the TFT circuit stretching.
due to mechanical stress from bending or such that when gaps are generated,
stretching, electric stress from electrostatic the open current induces the particles The authors also describe a strategy for
discharge arising from human contact or to align and form a conductive bridge, efficiently packaging these particles in
corrosion from moisture or sweat. Could thereby completing the circuit and TFT circuits for large-scale manufacturing.
their durability be enhanced by employing “healing” it. Such particles can This could potentially widen the scope of
self-healing TFT circuits? only align in the presence of an applications of flexible electronic devices.
open current, and otherwise remain
Researchers from the Department of dispersed and insulated in the circuit. - Sukriti Kapoor
Instrumentation and Applied Physics, IISc,
KERNEL | ISSUE 3, 2021 | Pg 6
Photo courtesy: Satyaghosh Maurya
BIOLOGY THROUGH AN
ENGINEER’S EYE
RAHUL ROY’S LAB AIMS TO ENGINEER NOVEL SOLUTIONS FOR BIOLOGICAL PROBLEMS
Nine years ago, when Rahul Roy was these steps and develop more effective and collaborative studies, the group found that
applying to IISc for a faculty position, he safer treatments in a shorter time. subunits of this toxin assemble into the
gave presentations at several departments, ring in any random sequence and that the
because he wasn’t sure where he would Biologists with an engineering background assembly is reversible — when incomplete
fit in best. Although he was interested like Rahul are using a combination of structures are formed, some previously
in both engineering and science, he traditional biological techniques and new built structures can break up and release
didn’t foresee working in an engineering computational approaches to address such bits that join and complete the partial
department. Eventually, however, he joined challenges. His lab is currently developing structures.
the Department of Chemical Engineering as general “rules” that will help decrypt
an Assistant Professor, where he has been biological diversity at the molecular A third area of interest is understanding
pursuing diverse projects at the intersection level and perhaps develop treatments how viruses like the novel coronavirus,
of engineering and biology. without running clinical trials. “[While] we SARS-CoV-2, mutate. In just the past
understand that there’s still going to be few months, new SARS-CoV-2 variants
Rahul’s lab, in his own words, is working a large heterogeneity, we’ll still come up have emerged. As the virus replicates,
towards the ambitious goal of making biology with rules which will explain the overall mutations arise and eventually accumulate
more “predictive”. Biological systems are behaviour,” he says. in its genome. Errors during replication
inherently complex and heterogeneous. Take happen because RNA polymerase – the
for instance the human body. Scientists still Towards this goal, Rahul’s lab is interested enzyme that creates copies of the virus – is
don’t know enough about how the different in using single-molecule imaging to study inefficient. “Now, every time it [the virus]
parts of our body work. This is because within how different copies of the same molecule is making a copy of itself, it is actually
each part, different cells behave differently. carry out the same function differently. Take creating a variant,” Rahul explains. This
And within each cell, different molecules the rate at which an enzyme catalyses a leads to the accumulation of multiple
behave differently. This heterogeneity is a biological reaction, for instance. The value variants of the same virus inside a host
major problem in biology research; we cannot that scientists assign to it is merely the cell, which requires the use of antivirals
tell when a molecule will act differently. average of the rates for multiple copies of that can simultaneously act on all of them.
the same enzyme. Even little modifications to
This is also an issue when it comes to the enzyme’s structure can affect its catalytic Using a technique called single virus
developing drugs and vaccines, which is activity drastically. sequencing, Rahul’s group has been able
now a painfully long process. Even after a to discern the exact number of variants
molecule with therapeutic properties has Another direction of his lab’s work is on the present in a blood sample. In another
been discovered, scientists need to test it first self-assembly of viruses and bacterial pore- project, they have developed a method
on cells in the lab, and then on animals, and forming toxins. Understanding how these to count the number of RNA molecules
finally perform clinical trials on humans to toxins assemble can help scientists find that correspond to a particular gene in
understand if they are safe and effective. But ways to block the bacteria from entering our individual cells, by trapping a cell in
if researchers are able to better predict how cells and causing infections. A toxin found a drop of a water-in-oil emulsion. This
our bodies would react to such treatments, it in some bacteria, called Cytolysin A, forms a approach has helped them understand
would be easier for them to bypass some of 12-sided ring-like structure. In one of their the exact concentration of a specific RNA
KERNEL | ISSUE 3, 2021 | Pg 7
Artistic rendition of the pore-forming toxin action on cell membranes (Image courtesy: Satyaghosh Maurya)
molecule in each cell. Adding microfluidics to In recent months, Rahul’s lab has also postdocs, which has often resulted in him
this approach allows them to study many cells been working on projects related to pursuing areas that he never anticipated he
simultaneously. COVID-19. They have developed a rapid would be working on, like microfluidics.
antibody test for COVID-19. A home-based
Yet another interest of Rahul’s lab involves test kit is also in the making, which aims He says that his motivation to pursue
building tools for sensing and lab-on-chip to use antibody fragments to enrich research comes from the sheer joy of
devices. His team has recently developed and detect the virus concentration in finding out something for the first time.
a smartphone-based antibiotic sensing easily available biofluids like saliva. It Seeing the eyes of budding young scientists
approach, where sensors made up of DNA can further intensify the signal using an light up with joy when they understand
molecules, called DNA aptamers, are used to isothermal amplification technique at a new concept also keeps him going.
detect the presence of an antibiotic. When the 37°C. This kit can display results within Students, being “naive”, often bring a
sensor detects the antibiotic, dyes attached to 20 to 30 minutes and can be used without unique perspective to a research problem
it exhibit a change in either the fluorescence professional assistance by anyone who is because they do not carry the burden of
colour or intensity that can be easily detected not able to visit a pathology lab. preconceived notions, he says. “And that’s
by a smartphone camera. Such sensors why we always want not one person, but
can be designed to detect other kinds of Exploring multiple projects can be hard. hundreds of people approaching the same
chemicals as well. Rahul believes that, in the Rahul explains that the reason why he problem from different angles.”
future, pluggable adapters for smartphones ended up pursuing so many diverse
might help convert them into point-of-care projects is that he designs these with - Debraj Manna
diagnostic devices. major inputs from his students and
Snapshot of a section of the single-molecule imaging set up in the Nanobiology Lab (Photo courtesy: Satyaghosh Maurya)
Office of Communications (OoC) EDITORIAL TEAM DESIGN
Indian Institute of Science (IISc) Deepika S TheFool.in
Karthik Ramaswamy
Bengaluru - 560012
Ranjini Raghunath (Coordinator)
kernel.ooc@iisc.ac.in | office.ooc@iisc.ac.in Samira Agnihotri
Vaishalli Chandra
KERNEL | ISSUE 3, 2021 | Pg 8
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