–Akash Kalita

From left to right; Abhilash Vijay Nair, Anmol Singh, Dipshikha Chakravortty
(Credit: DC Lab/IISc)

Food-borne diseases like typhoid, caused by Salmonella Typhimurium, are a severe threat to public health, especially in India. The indiscriminate use of antibiotics has allowed this bacterium to become resistant, posing a major hurdle in treating infections.   
“Salmonella’s strategies to survive are par excellence. With an increase in antimicrobial resistance in Salmonella, it is just impossible to eradicate,” says Dipshikha Chakravortty, Professor in the Department of Microbiology and Cell Biology (MCB), Indian Institute of Science (IISc).   

In a recent study published in Redox Biology, she and her team have pinpointed how the bacterium uses a key molecule called spermidine to shield itself from the onslaught of the host’s defence machinery. They also find that an existing FDA-approved drug can reduce spermidine production, weakening the bacterium's ability to cause infection.  

When Salmonella infects a host, it is engulfed by macrophages, cells that are part of the host’s immune system. After engulfment, macrophages start increasing the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) inside themselves. This creates a hostile environment for the bacteria to survive.   

One of the key molecules that Salmonella seems to depend on is a polyamine called spermidine. Not only does the bacteria synthesise its own spermidine, but also hijacks the host machinery to produce more of the molecule.   

In the current study, the researchers found that spermidine is crucial for Salmonella to protect itself from oxidative stress inside the macrophages. Spermidine specifically regulates the expression of an enzyme called GspSA, which causes spermidine to bind strongly to a protein called Glutathionyl (GSH). This conjugate forms chemical bonds with various bacterial proteins, strengthening and shielding them during oxidative stress. Mice infected with mutant Salmonella lacking the ability to import and produce spermidine showed higher survival rates compared to the ones infected with normal Salmonella.  

“Spermidine from both bacteria and the host acts like a robust weapon for Salmonella to safeguard against reactive oxygen species,” explains Chakravortty.   

With this revelation, the team began looking for drugs that could deplete spermidine levels in the host.   

The team focused on D, L-alpha-difluoromethylornithine (DFMO), an FDA-approved drug used widely for treating human African trypanosomiasis. They found that DFMO irreversibly blocks ornithine decarboxylase, an enzyme involved in a key step of the spermidine biosynthesis pathway in the host, reducing its levels and making the bacteria more vulnerable. Mice which were administered the drug showed better survival rates.    

“Since we are targeting the host machinery, and not targeting the bacteria, it will not evolve genetically,” explains Abhilash Vijay Nair, a former PhD student at MCB and the first author of the paper.   

DFMO also acts on another enzyme called arginase, which is responsible for ensuring that an amino acid called arginine is available for spermidine synthesis. When arginase is blocked, less spermidine is synthesised, again making the bacteria more susceptible to oxidative stress. DFMO is, therefore, a promising candidate for treating salmonellosis, the researchers say. In future studies, they seek to pinpoint other players that might be involved in controlling spermidine synthesis.    

REFERENCE:  
Nair AV, Singh A, Rajmani RS, Chakravortty D, Salmonella Typhimurium employs spermidine to exert protection against ROS-mediated cytotoxicity and rewires host polyamine metabolism to ameliorate its survival in macrophages, Redox Biology (2024).  
https://linkinghub.elsevier.com/retrieve/pii/S2213231724001277
  
CONTACT:
Dipshikha Chakravortty   
Professor  
Department of Microbiology and Cell Biology (MCB)  
Indian Institute of Science (IISc)  
Email: dipa@iisc.ac.in  
Phone: 080-2293 2842  
Lab website: https://mcbl.iisc.ac.in/dclab/  

NOTE TO JOURNALISTS:  
a) If any of the text in this release is reproduced verbatim, please credit the IISc press release. 
b) For any queries about IISc press releases, please write to news@iisc.ac.in or pro@iisc.ac.in.   
Attendee panel closed

21 March 2024
– Sandeep Menon

A new approach by researchers at the Indian Institute of Science (IISc) seeks to use multiple swarms of drones to tackle natural disasters like forest fires.

Forest fires are becoming increasingly catastrophic across the world, accelerated by climate change.

“A swarm of drones could be the solution,” says Suresh Sundaram, Professor in the Department of Aerospace Engineering, IISc. Although they have not yet been used in India, the use of drones is not entirely new. But in a new study, Sundaram’s team proposes taking the technology a step further: Coordinated multi-swarm drones swooping in to quell forest fires.

“By the time somebody identifies and reports a fire, it has already started spreading and cannot be put out with one drone,” says Sundaram. “You need to have a swarm of drones. A swarm that can communicate with each other.”

The solution was to design a special kind of algorithm that would allow the swarm to communicate with each other as well as make independent decisions. In a hypothetical scenario, when an alarm is raised about a potential fire, the swarms can be sent in, each drone armed with cameras, thermal and infrared sensors, and temperature detectors, to spot the fires. Once the fire is discovered, the drone closest to it becomes the centre of the swarm and attracts others towards it. Interestingly, each drone will also have autonomy to calculate the fire’s size and potential spread, and decide how many drones are needed to quench the fire.

“These decisions are made by the drones,” says Sundaram. “They figure out which cluster of fire is going to spread faster, and allocate the required number of drones to put out that fire while the others look for other fire clusters.”

Multiple swarms of drones for testing the proposed approach for disaster management. The image depicts search and mitigation for two targets illustrated as white circles by three swarms of drones (Photo: Artificial Intelligence and Robotics Laboratory, Department of Aerospace Engineering, Indian Institute of Science)

The swarm-based search algorithm developed by the team is key to controlling the drones’ behaviour. Searching for fire cannot be random as the area to explore would be too large. To address this, the researchers took inspiration from the foraging behaviour of a marine predator, a flagellum called Oxyrrhis marina.

“When foraging, it firsts take longer steps to explore the area. Once it feels like it is closer to the food source, it will reduce the step length and then start exploring the area in more detail,” explains Josy John, PhD student at the Department of Aerospace Engineering, and lead author of the study published in IEEE Transactions on Systems, Man, and Cybernetics: Systems. The team decided to incorporate this behaviour into their algorithm. “The temperature sensors in the drones look for a minimum [threshold] value. When that is reached, the drones reduce their search step, because the fire is near,” John adds.

The advantage of using drones, Sundaram points out, is that the decision-making is decentralised, based on data, and aimed at maximum efficiency. No more than the required number of drones will be assigned to a fire cluster, allowing others to fan out in search of other clusters.

The researchers have tested specific components of the approach, such as the AI-enabled fire detection using thermal cameras, and accurate payload drop mechanism for fire extinguisher deployment. Full-scale search and mitigation by the swarm is yet to undergo field-testing. Going forward, they plan to combine such drone swarms with unmanned ground vehicles that can carry resources and serve as refuelling stations.

Such drone swarms can also be helpful during other natural disasters like floods and earthquakes, to locate survivors, deliver water, food and medicines; and boost communication.

REFERENCE:

John J, Harikumar K, Senthilnath J, Sundaram S, An Efficient Approach With Dynamic Multiswarm of UAVs for Forest Firefighting, IEEE Transactions on Systems, Man, and Cybernetics: Systems (2024).

CONTACT:

Suresh Sundaram
Professor
Department of Aerospace Engineering
Indian Institute of Science (IISc)
Email: vssuresh@iisc.ac.in
Phone: +91-80-22932755
Website: https://aero.iisc.ac.in/people/suresh-sundaram/

NOTE TO JOURNALISTS:
a) If any of the text in this release is reproduced verbatim, please credit the IISc press release.
b) For any queries about IISc press releases, please write to news@iisc.ac.in or pro@iisc.ac.in.

19 March 2024
– Sankeerthana Avasarala

Sample exhibiting colour change from blue to yellow on bending, by virtue of changing gallium nanostructures (Photo: Mark Vailshery)

Researchers at the Indian Institute of Science (IISc) have developed flexible films that exhibit bright colours purely by virtue of their physical structure, without the need for any pigment. When stretched, the films exhibit a change in colour as a response to the mechanical deformation.

To design these films, the team devised a novel cost-effective and scalable single-step technique that involves evaporating gallium metal to form nano-sized particles on a flexible substrate. Their method allows the simultaneous fabrication of multiple structural colours responsive to mechanical stimuli.

The team has also shown how these films can be used for a variety of applications, from smart bandages and movement sensors to reflective displays.

“This is the first time that a liquid metal like gallium has been used for photonics,” says Tapajyoti Das Gupta, Assistant Professor in the Department of Instrumentation and Applied Physics (IAP), and corresponding author of the study published in Nature Nanotechnology.

Some natural objects like gemstones, mollusc shells or peacock feathers are inherently colourful. Their colours emerge from the interaction of light with micro- or nano-structures arranged periodically, such as tiny silica spheres in opal, calcium carbonate-based platelets in mollusc shells, and segmented ribbons atop cylindrical structures in peacock feathers.

Nature-inspired structurally coloured materials have found broad applications in displays, wearable electronics, visual sensors, and anti-counterfeiting tags. In recent years, scientists have been trying to design materials which can change colour in response to an external mechanical stimulus.

Sample exhibiting colour change from pink to green on local application of force with a tweezer tip (Photo: Alwar Samy Ramasamy)

The IISc team began experimenting with gallium, which has not been explored for such applications because its high surface tension hinders the formation of nanoparticles. Gallium is a liquid metal at room temperature and its nanoparticles have been shown to have strong interactions with electromagnetic radiation. The process developed by the team achieves the feat of overcoming the barrier of surface tension to create gallium nanoparticles, by cleverly using the properties of a substrate called polydimethylsiloxane (PDMS), a biocompatible polymer.

When the substrate was stretched, the researchers noticed something unusual. The material started showing different colours depending on the strain. The researchers theorised that the array of deposited gallium nanoparticles interacts with light in specific ways to generate the colours.

To understand the role of the substrate in colour generation, the team developed a mathematical model.

PDMS is a polymer made by mixing two liquid-like components – an oligomer and a cross-linker – which react with each other to form a solid polymer. What the researchers found is that the unreacted portion of oligomer, which is still in a liquid state, played a crucial role in stabilising the formation of gallium nanoparticles on the substrate. When this substrate is then stretched, the liquid-like oligomers seep into the gaps between the nanoparticles, changing the gap size and their interaction with light, resulting in the observed change in colouration. Experiments carried out in the lab confirmed the model’s predictions. By tuning the ratio of the oligomer content to the cross-linker, the researchers obtained a gamut of colours.

“We show that the PDMS substrate not only holds the structure, but also plays an active role in determining the structure of gallium nanoparticles and resulting colouration,” says Renu Raman Sahu, PhD student in IAP and lead author. Even after 80,000 cycles of stretching, the material was able to show a repeatable colour change, indicating its reliability.

From left to right: Tapajyoti Das Gupta, Renu Raman Sahu, Mark Vailshery and Alwar Samy Ramasamy (Photo: Renu Raman Sahu)

Conventional techniques such as lithography used to fabricate such materials involve many steps and are costly to scale up. To circumvent this, the team devised a single-step physical vapour deposition technique to evaporate the liquid gallium metal and deposit it on the PDMS substrate. This allowed them to fabricate flexible, structurally coloured films measuring about half the size of a palm.

There are various applications possible for such films. The team demonstrated one such application: a body movement sensor. A strip of the film, when attached to the finger, changed colour when the finger was bent, helping to sense movement in real time. Sahu says, “In the future, these materials could be used for energy harvesting applications as well.”

REFERENCES:
Sahu RR, Ramasamy AS, Bhonsle S, Vailshery M, Archana S, Kumar H, Das Gupta T, Single-step fabrication of liquid gallium nanoparticles via capillary interaction for dynamic structural colours, Nature Nanotechnology (2024).

Sahu RR, Das Gupta T, Fabrication of mechanochromic gallium nanostructures by capillary interactions, Nature Nanotechnology (2024).

Sahu RR, Ramasamy AS, Gap-plasmonic tuneable structural colors by capillary interactions.

CONTACT:
Tapajyoti Das Gupta
Assistant Professor
Department of Instrumentation and Applied Physics (IAP)
Indian Institute of Science (IISc)
Email: tapajyoti@iisc.ac.in
Phone: +91-80-2293-2349
Website: http://iap.iisc.ac.in/~tapajyoti/

NOTE TO JOURNALISTS:
a) If any of the text in this release is reproduced verbatim, please credit the IISc press release.
b) For any queries about IISc press releases, please write
to news@iisc.ac.in or pro@iisc.ac.in.

2

Exploring the link between attention and eye movements (Image courtesy: Priyanka Gupta/Pixabay).

Two new studies from the Centre for Neuroscience (CNS), Indian Institute of Science (IISc) explore how closely attention and eye movements are linked, and unveil how the brain coordinates the two processes.

Attention is a unique phenomenon that allows us to focus on a specific object in our visual world, and ignore distractions. When we pay attention to an object, we tend to gaze towards it. Therefore, scientists have long suspected that attention is tightly coupled to rapid eye movements, called saccades. In fact, even before our eyes move towards an object, our attention focuses on it, allowing us to perceive it more clearly – a well-known phenomenon called pre-saccadic attention.

However, in a new study published in PLOS Biology, the researchers at CNS show that this perceptual advantage is lost when the object changes suddenly, a split second before our gaze falls upon it, making it harder for us to process what changed.

“Our study provides an interesting counterpoint to many previous studies which suggested that pre-saccadic attention is always beneficial,” explains Devarajan Sridharan, Associate Professor at CNS and corresponding author of the study.

In the PLOS Biology study, Priyanka Gupta, a PhD student in Sridharan’s lab, trained human volunteers to covertly monitor gratings (line patterns) presented on a screen, without directly looking at them, and to report when one tilted slightly. “Importantly, the participants did this task just before their eyes moved, in the pre-saccadic window. So, we were able to study the relationship between pre-saccadic attention and the detection of changes in the visual environment,” explains Gupta. A tracker was used to monitor their eye movements before, during and after their gaze fell on the object. “To our surprise, participants found it harder to detect the changes in the pre-saccadic window,” Gupta adds.

In a follow-up experiment, they made the participants monitor two gratings presented one after the other quickly, again, just before their eyes moved. What the team found was that if the orientation of the second grating suddenly changed during this time, the participants tended to mix up the orientations of the two gratings – explaining the loss of the attentional advantage.

“This is essentially a basic science study,” says Sridharan. But such insights, he adds, can be useful for how we track multiple objects in rapidly changing environments – in driving or flight simulators, for example.

In the other study published in Science Advances, carried out with collaborators at Stanford University, the researchers used an unusual experiment – this time, to decouple attention from eye movements – in monkeys. Their goal was to tease out what is happening in the brain while these processes play out.

The monkeys had been trained on a counter-intuitive task called an “anti-saccade” task. Like the human study, the monkeys covertly monitored several gratings on a computer screen without directly looking at them. But when any one grating tilted slightly, the monkeys had to look away from it instead of focusing more sharply on it. This helped the researchers delink the location of the monkey’s attention, from the location where its gaze ultimately fell.

Using a special kind of electrode called a “U-probe”, they also recorded signals from hundreds of neurons across different layers of a specific region in the monkey’s brain called the visual cortex area V4. What they found was that neurons in the more superficial layers of the cortex generated attention signals, while neurons in deeper layers produced eye movement signals.

Interestingly, these neurons also showed different activity patterns. “The superficial neurons increased their firing rates, to signal the object that needs to be attended to and prioritised for decision-making,” says Adithya Narayan Chandrasekaran, first author of the Science Advances study and a former research assistant in Sridharan’s lab at CNS. On the other hand, the deep neurons were tuning down their “noise”, possibly to allow the animal to perceive the object better.

The researchers believe that uncovering such brain signatures can eventually point to what fails in attention disorders. Sridharan says, “Discovering such mechanisms is vital for developing therapies for disorders like ADHD.”

REFERENCES:

Gupta P, Sridharan D, Presaccadic attention does not facilitate the detection of changes in the visual field, PLOS Biology (2024)

Chandrasekaran AN, Vermani A, Gupta P, Steinmetz N, Moore T, Sridharan D, Dissociable components of attention exhibit distinct neuronal signatures in primate visual cortex, Science Advances (2024)

CONTACT:

Devarajan Sridharan
Associate Professor
Centre for Neuroscience (CNS)
Indian Institute of Science (IISc)
Email: sridhar@iisc.ac.in
Phone: 080-22933434/22933431
Website: https://cns.iisc.ac.in/sridhar/

NOTE TO JOURNALISTS:

a) If any of the text in this release is reproduced verbatim, please credit the IISc press release.
b) For any queries about IISc press releases, please write to news@iisc.ac.in or pro@iisc.ac.in.

22 February 2024

An Indian spectacled cobra (a member of the Elapidae family of snakes) on the IISc campus (Photo: Kartik Sunagar)

Scientists at the Scripps Research Institute and the Evolutionary Venomics Lab (EVL) at the Centre for Ecological Sciences (CES), Indian Institute of Science (IISc) have developed a synthetic human antibody that can neutralise a potent neurotoxin produced by the Elapidae family of highly toxic snakes, which includes the cobra, king cobra, krait and black mamba.

The team adapted an approach used earlier to screen for antibodies against HIV and COVID-19 in order to synthesise the new venom-neutralising antibody. “This is the first time that this particular strategy is being applied to develop antibodies for snakebite treatment,” says Senji Laxme RR, PhD student at EVL, CES and co-first author of the study published in Science Translational Medicine.

The researchers say that this development takes us one step closer to a universal antibody solution that can offer broad protection against a variety of snake venoms.

Snakebites cause thousands of deaths every year, especially in India and sub-Saharan Africa. The current strategy for developing antivenoms involves injecting snake venom into equines like horses, ponies and mules, and collecting antibodies from their blood. But there are several problems.

“These animals get exposed to various bacteria and viruses during their lifetime,” explains Kartik Sunagar, Associate Professor at CES and joint corresponding author of the study. “As a result, antivenoms also include antibodies against microorganisms, which are therapeutically redundant. Research has shown that less than 10% of a vial of antivenom actually contains antibodies that are targeted towards snake venom toxins.”

The antibody developed by the team targets a conserved region found in the core of a major toxin called the three-finger toxin (3FTx) in the elapid venom. Although different species of elapids produce different 3FTxs, a handful of regions in the protein are similar. The team zeroed in on one such conserved region – a disulphide core. They designed a large library of artificial antibodies from humans, which were displayed on yeast cell surfaces. They then tested the antibodies’ ability to bind to 3FTxs from various elapid snakes around the world. After repeated screening, they narrowed down their choices to one antibody that could bind strongly to various 3FTxs. Among the 149 variants of 3FTxs in public repositories, this antibody could bind to 99.

The researchers then tested their antibody in animal models. In one set of experiments, they pre-mixed the synthetic antibody with a toxic 3FTx produced by the Taiwanese banded krait, and injected it into mice. Mice given just the toxin died within four hours. But those given the toxin-antibody mix survived past the 24-hour observation window and looked completely healthy.

The team also tested their antibody against the whole venom of the monocled cobra from Eastern India and the black mamba from sub-Saharan Africa, and found similar results. The efficacy of the antibody was found to be nearly 15 times that of the conventional product. Crucially, when they first injected the venom and then gave the antibody after a time delay – 0 minutes, 10 minutes and 20 minutes – the antibody was still able to save mice. The conventional product, however, only worked well when injected alongside the venom. A delay of even 10 minutes significantly reduced the potency of the conventional antivenom.

In addition, the team used cryo-EM to tease out the crystal structure of the toxin-antibody complex, and found that their binding was very similar to the binding between the toxin and receptors found in muscles and nerve cells. “Our antibody seems to mimic the toxin-binding site of the receptor in our body,” says Sunagar. “Venom toxins, therefore, are binding to our antibody instead of the receptor. Since our antibody neutralises venom even with delayed administration, it may suggest that it can displace toxins that are bound to receptors.”

The researchers used human-derived cell lines to produce the antibody, bypassing the need to inject the venom first into animals like horses. “Because the antibody is fully human, we don’t expect any off-target or allergic responses,” Laxme adds.

“This solves two problems at the same time,” says Sunagar. “First, it is an entirely human antibody and, hence, side-effects, including fatal anaphylaxis, occasionally observed in patients being treated with conventional antivenom, can be prevented. Secondly, this would mean that animals need not be harmed in future to produce this life-saving antidote.”

The same approach can be used to develop antibodies against other snake venoms too, which can then be combined into a single antivenom therapy. On taking this forward to clinical trials, Sunagar says, “At this stage, a clinician cannot rely on this single antibody for treatment as this is only effective against certain elapid snakes. We are in the process of discovering additional antibodies against other snake venom toxin targets. A universal antivenom in future would consist of a couple of such synthetic antibodies that would hopefully neutralise venoms of most snakes in various parts of the world. A universal product, or at least a cocktail of antibodies that work pan-India, could then be taken to human clinical trials.”

KANNADA VERSION OF PRESS RELEASE:

https://drive.google.com/file/d/10AMgopkeZO82jI_BsXuxJeEIdlNlklcX/view?usp=sharing

REFERENCE:

Khalek IS, Senji Laxme RR, Nguyen YTK, Khochare S, Patel RN, Woehl J, Smith JM, Saye-Francisco K, Kim Y, Mindrebo LM, Tran Q, Kędzior M, Boré E, Limbo O, Verma M, Stanfield RL, Menzies SK, Ainsworth S, Harrison RA, Burton DR, Sok D, Wilson IA, Casewell NR, Sunagar K, Jardine JG, Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins, Science Translational Medicine (2024).

CONTACT:

Kartik Sunagar
Associate Professor
Centre for Ecological Sciences (CES)
Indian Institute of Science (IISc)
Email: ksunagar@iisc.ac.in
Phone: 080-2293-2896
Website: https://www.venomicslab.com/

Joseph Jardine
Assistant Professor
Department of Immunology and Microbiology
Scripps Research
Email: jardine@scripps.edu
Phone: (858) 784-8135
Website: https://www.scripps.edu/faculty/jardine/

NOTE TO JOURNALISTS:

a) If any of the text in this release is reproduced verbatim, please credit the IISc press release.

b) For any queries about IISc press releases, please write to news@iisc.ac.in or pro@iisc.ac.in.

15 February 2024

– Sandeep Menon

A paper-based platform developed by researchers at the Indian Institute of Science (IISc) and Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) could help quickly detect the presence of antibiotic-resistant, disease-causing bacteria.

One of mankind’s greatest challenges has been the rise of disease-causing bacteria that are resistant to antibiotics. Their emergence has been fuelled by the misuse and overuse of antibiotics.

A handful of such bacteria – including E. coli and Staphylococcus aureus – have caused over a million deaths, and these numbers are projected to rise in the coming years, according to the World Health Organisation. Timely diagnosis can improve the efficiency of treatment.

“Generally, the doctor diagnoses the patient and gives them medicines. The patient then takes it for 2-3 days before realising that the medicine is not working and goes back to the doctor. Even diagnosing that the bacteria is antibiotic-resistant from blood or urine tests takes time. We wanted to reduce that time-to-diagnosis,” says Uday Maitra, Professor at the Department of Organic Chemistry, IISc.

In a paper published in ACS Sensors, Maitra’s lab and collaborators have addressed this challenge. They have developed a rapid diagnosis protocol that uses a luminescent paper-based platform to detect the presence of antibiotic-resistant bacteria.

Schematic depicting the detection/differentiation of antibiotic-resistance bacteria (Image: Arnab Dutta)

There are different ways by which a bacterium becomes resistant to antibiotics. In one, the bacterium evolves, and can recognise and eject the medicine out of its cell. In another, the bacterium produces an enzyme called β-lactamase, which hydrolyses the β-lactam ring – a key structural component of common antibiotics like penicillin and carbapenem – rendering the medication ineffective.

The approach developed by the IISc and JNCASR team involves incorporating biphenyl-4-carboxylic acid (BCA) within a supramolecular hydrogel matrix containing terbium cholate (TbCh). This hydrogel normally emits green fluorescence when UV light is shined on it.

“In the lab, we synthesised an enzyme-substrate by tethering BCA to the cyclic [β-lactam] ring that is a part of the antibiotic. When you mix this with TbCh hydrogel, there is no green emission as the sensitiser is ‘masked,’” explains Arnab Dutta, PhD student in the Department of Organic Chemistry, IISc, and lead author of the paper. “In the presence of β-lactamase enzyme, the gel will produce green emission. β-lactamase enzyme in the bacteria is the one that cuts open the drug, destroys, and unmasks the sensitiser BCA. So, the presence of β-lactamase is signalled by green emission.” The luminescence signals the presence of antibiotic-resistant bacteria, and the intensity of the luminescence indicates the bacterial load. For non-resistant bacteria, the green intensity was found to be extremely low, making it easier to distinguish them from resistant bacteria.

The next step was to find a way to make the technology inexpensive. Currently used diagnostics instruments are costly, which drives up the price for testing.

The team collaborated with a Tamil Nadu-based company called Adiuvo Diagnostics to design a customised, portable and miniature imaging device, named Illuminate Fluorescence Reader. Infusing the hydrogel in a sheet of paper as the medium reduced the cost significantly. The instrument is fitted with different LEDs that shine UV radiation as required. Green fluorescence from the enzyme is captured by a built-in camera, and a dedicated software app measures the intensity, which can help quantify the bacterial load.

Portable fluorescence reader device (Photo: Arnab Dutta)

The team from IISc tied up with Jayanta Haldar’s research group from JNCASR to check their approach on urine samples. “We used samples from healthy volunteers and added pathogenic bacteria to mimic Urinary Tract Infections. It successfully produced the outcome within two hours,” explains Maitra.

As the next step, the researchers plan to tie up with hospitals to test this technology with samples from patients.

REFERENCE:

Dutta A, Mukherjee S, Haldar J, Maitra U, Augmenting Antimicrobial Resistance Surveillance: Rapid Detection of β-Lactamase-Expressing Drug-Resistant Bacteria through Sensitized Luminescence on a Paper-Supported Hydrogel, ACS Sensors (2024).

CONTACT:

Uday Maitra
Honorary Professor
Department of Organic Chemistry
Indian Institute of Science (IISc)
Email: maitra@iisc.ac.in
Phone: +91-80-2293-2690
Lab website: https://orgchem.iisc.ac.in/uday-maitra/

Arnab Dutta
PhD student
Department Of Organic Chemistry
Indian Institute of Science (IISc)
Email: arnabdutta@iisc.ac.in

NOTE TO JOURNALISTS:

a) If any of the text in this release is reproduced verbatim, please credit the IISc press release.

b) For any queries about IISc press releases, please write to news@iisc.ac.in or pro@iisc.ac.in

12 February 2024

31 January 2024

The 42nd meeting of the Astronomical Society of India will be taking place this week at Indian Institute of Science (IISc), Bengaluru. The meeting is jointly organised by IISc, Indian Space Research Organisation (ISRO) and the JN Planetarium. There will be a press meet on January 31, 2024, at 6.30 pm at the JN Tata Complex, to discuss the upcoming astronomy initiatives and conference details. The formal inauguration of the event is set to take place at 9.30 am on February 1, 2024, at the JN Tata Main Auditorium, IISc.

Scientific discourses focussing on the sun, planets, black holes and beyond will be held from 31 January to 4 February, 2024. Popular events for citizens and school students will be offered throughout the week. About 750 astronomers are expected to be in attendance for the meeting.

Special attractions this year include the release of the Astronomy Vision – a document which includes the culmination of a nationwide exercise to imagine the future of cosmic exploration from India, a workshop on the recently launched AdityaL1 mission – India’s first space based solar observatory, plenary lectures highlighting India’s planetary exploration program and pulsar timing array initiatives. The ASI awards which will be given out during the inaugural function, recognises and honours the contributions of students, scientists and citizens to astronomy and astrophysics research as well as capacity building activities.

More details of the meeting are available at: https://astron-soc.in/asi2024.

A number of events have been separately planned for the common citizens and school students. The Public Outreach and Education Committee of the Astronomical Society of India is partnering with local organisers and astronomy industries to host popular lectures on themes ranging from space exploration to the role of astronomy in defining time and calendars. There are lectures planned on astrophotography, with a special showcase on the night skies of the Indian Himalayas and the need to preserve the heritage of the skies. Solar and night sky observation events have been organised and a star party is planned at the JN Planetarium.

A detailed agenda of events open to the public is available at: https://astron-soc.in/outreach/

CONTACT:

Local Organising Committee:
Banibrata Mukhopadhyay
Professor
Department of Physics
Indian Institute of Science (IISc)
Email: bm@iisc.ac.in

Astronomical Society of India (ASI): astron.soc.india@gmail.com

Office of Communications (OoC)
Indian Institute of Science (IISc)
Email: news@iisc.ac.in

NOTE TO JOURNALISTS:
a) If any of the text in this release is reproduced verbatim, please credit the IISc press release.
b) For any queries about IISc press releases, please write to news@iisc.ac.in or pro@iisc.ac.in.

16-01-2024

–Pratibha Gopalakrishna

Ovarian cancer is dangerous because it often goes undetected until it has spread beyond the ovaries, and the symptoms can also be attributed to other conditions. Scientists believe that ageing can increase the spread of ovarian and other cancers, but the underlying mechanisms are not fully clear. Now, researchers at the Indian Institute of Science (IISc) have found that ovarian cancer cells can spread more easily in tissues that are senescent or aged because these tissues secrete a unique extracellular matrix that attracts the spreading cancer.

Senescent mesothelial matrix attracts ovarian cancer cells, aiding their adhesion and spread (Credit: Ramray Bhat, created on Biorender)

The researchers used a chemotherapy-induced senescent model to study this phenomenon. They first extracted tissues found in the lining of body cavities from mice models and exposed half of these tissues to chemotherapeutics that are used to treat cancer, pushing them to senescence – a state in which the cells stop replicating but don’t die. “What you might call in a body ageing, in a cell or tissue you would call it senescence,” explains Ramray Bhat, Associate Professor at the Department of Developmental Biology and Genetics (DBG) and corresponding author of the study published in Cellular and Molecular Life Sciences.

The team then exposed both young and aged mouse tissues and human tissue-like cell sheets to ovarian cancer cells. They used time-lapse imaging to tag the normal and cancer cells with different fluorescent markers so that they could be studied under a microscope for extended periods of time. “It’s slightly harder to image tissues when compared to cell lines as the latter has only one particular cell type growing,” explains Bharat Thapa, first author and former biology undergraduate student at IISc, now pursuing a PhD at Vanderbilt University, USA.

What they found was that the cancer cells chose to settle down more on the aged tissues; moreover, they settled closer to the aged normal cells in the cell sheets.

To figure out what was drawing the cancer cells to the aged cells, the team first wondered if they were being attracted to signalling molecules that were being secreted by the aged cells and diffusing over long distances. They built computer models to explore the interactions between the cancer cells and the aged cells.

What they found was surprising: It was not the diffusing molecules that were luring the cancer cells. It was proteins secreted by aged cells that settle down as the extracellular matrix (ECM) – the base on which the cells adhere and grow – that were calling the cancer cells. “The extracellular matrix is what was bringing the cancer cells there and allowing them to better attach near the aged cells and spread faster,” says Bhat.

The team also carried out experiments on human cell lines to replicate the predictions of the computer simulations. They noticed that the cancer cells stuck strongly to the extracellular matrix around the aged cells, and eventually cleared the aged cells away. They also noticed that the aged ECM had higher levels of proteins such as fibronectin, laminin and hyaluronan compared to the young cells’ ECM, which allowed the cancer cells to bind more strongly.

Based on their findings, the researchers suggest that this could potentially be one of the reasons why aged populations typically tend to have worse outcomes in cancer than younger populations. “The fact is that chemotherapy also induces senescence, and that senescence can make things worse,” says Bhat. “Appropriate use of chemotherapy could be very important in getting good outcomes in ovarian cancer.”

One way forward, adds Bhat, could be to focus on finding probes that can identify some of these matrix proteins, which can help predict where the cancer cells would get deposited in the tissues. Thapa also hopes that future studies will build a strong case for using senolytics – drugs that kill senescent cells – as a combination therapy with chemotherapeutics to tackle cancer progression.

REFERENCE:

Thapa BV, Banerjee M, Glimm T, Saini DK, Bhat R, The senescent mesothelial matrix accentuates colonization by ovarian cancer cells, Cellular and Molecular Life Sciences (2024).

The research was funded by the India Alliance DBT Wellcome Trust and the John Templeton Foundation.

CONTACT:

Ramray Bhat
Associate Professor
Department of Developmental Biology and Genetics (DBG)
Indian Institute of Science (IISc)
Email: ramray@iisc.ac.in
Phone: +91-80-22932764
Website: https://morphogenesisiisc.wixsite.com/home

Bharat Vivan Thapa
Former UG (Master of Science) student, Indian Institute of Science (IISc)
PhD student, Vanderbilt University
Email: bharat.v.thapa@vanderbilt.edu

NOTE TO JOURNALISTS:

a) If any of the text in this release is reproduced verbatim, please credit the IISc press release.

b) For any queries about IISc press releases, please write to news@iisc.ac.in or pro@iisc.ac.in

10 January 2024

– Mohit Nikalje

Since the beginning of the COVID-19 pandemic, Raghavan Varadarajan, Professor at the Molecular Biophysics Unit (MBU), Indian Institute of Science (IISc), and collaborators have been working on developing a heat-tolerant vaccine that can offer protection against different strains of SARS-CoV-2 – both current and future variants.

In a study published in npj Vaccines, they report the design of a synthetic antigen that can be manufactured as a potential COVID-19 vaccine candidate. They show that their vaccine candidate is effective against all current strains of SARS-CoV-2 and can be quickly adapted for future variants as well.

While current vaccines are proven to be effective against most SARS-CoV-2 strains, their efficacy has declined due to the virus’ rapid mutation. After analysing various proteins found in the virus, the researchers selected two parts of SARS-CoV-2’s spike protein – the S2 subunit and the Receptor Binding Domain (RBD) – for designing their vaccine candidate. The S2 subunit is highly conserved – it mutates much less than the S1 subunit, which is the target of most current vaccines. Scientists have also known that the RBD can provoke a strong immune response in the host. Therefore, the team created a hybrid protein called RS2 by combining these two components.

RS2 sequence conservation and protective efficacy
Top panel: Sequence conservation mapped onto a model of the RS2 molecule
Bottom Panel: Lung tissue sections from mice demonstrate superior protection conferred by RS2 against viral challenge
Credit: Nidhi Mittal

The researchers used mammalian cell lines to study the expression of the hybrid protein. “The protein showed very high levels of expression, and I [initially] thought that the experiment was not working properly,” says Nidhi Mittal, PhD student at MBU and first author of the study. This means, she explains, it can potentially be produced in large quantities.

The team then tested the effects of the protein in both mice and hamster models. They found that the hybrid protein triggered a strong immune response and provided better protection when compared to vaccines containing the whole spike protein.

The RS2 antigen can also be stored at room temperature for a month without the need for cold storage, unlike many vaccines on the market which require mandatory cold storage. This would make the distribution and storage of these vaccine candidates much more economical.

Varadarajan explains that his team began working on the vaccine even before the pandemic became widespread in India. “At that time, the Bill and Melinda Gates Foundation provided us funding and support,” he adds. Since 2000, Varadarajan’s team has been working on designing several viral vaccines, including those against AIDS and influenza. They have leveraged this expertise to design their current RS2-based COVID-19 vaccine candidate in collaboration with the startup Mynvax, that was, until recently, incubated at IISc.

According to the team, the vaccine candidate can be tailored to incorporate the RBD region of any new variant of SARS-CoV-2 that might emerge. Its high levels of expression and stability at room temperature can greatly reduce production and distribution costs, making it well suited for combating COVID-19.

REFERENCE:

Mittal N, Kumar S, Rajmani RS, Singh R, Lemoine C, Jakob V, Sowrabha BJ, Jagannath N, Bhat M, Chakraborty D, Pandey S, Jory A, Soundarya SAS, Kleanthous H, Dubois P, Ringe RP, Varadarajan R, Enhanced protective efficacy of a thermostable RBD-S2 vaccine formulation against SARS-CoV-2 and its variants, npj vaccines (2023).

CONTACT:

Raghavan Varadarajan
Professor
Molecular Biophysics Unit (MBU)
Indian Institute of Science (IISc)
Email: varadar@iisc.ac.in
Phone: 080-2293 3373
Website: http://mbu.iisc.ac.in/~rvgrp/home.html

Nidhi Mittal
PhD student
Molecular Biophysics Unit (MBU)
Indian Institute of Science (IISc)
Email: nidhimittal@iisc.ac.in

NOTE TO JOURNALISTS:

a) If any of the text in this release is reproduced verbatim, please credit the IISc press release.
b) For any queries about IISc press releases, please write to news@iisc.ac.in or pro@iisc.ac.in