Revolutionising TB research with 3D hydrogel model of lungs

by Hansraj Agrawal | Jul 21, 2024 | Science

“It is a very old bug and has evolved with us quite a bit,” says Rachit Agarwal, Associate Professor at the Department of Bioengineering, Indian Institute of Science, referring to Mycobacterium tuberculosis, a pathogen that kills 1.3 million every year.

Microbes mutate and develop resistance to existing drugs. When you develop new drugs, you need to test them.

Clinicians culture the bacteria on glass plates or petri dishes, but these do not properly mimic the 3D microenvironment inside lungs. Vishal Gupta, a PhD student explains the situation thus: “In a tissue culture plate, there are no extracellular matrix (ECM) molecules, and even if a very thin layer of ECM is coated on these plates, the lung cells ‘see’ the ECM on one side at best.”

To give those who culture the bacteria an environment closer to reality, researchers from the Department of Bioengineering, IISc, Bengaluru, have designed a 3D hydrogel culture system that “mimics the mammalian lung environment,” says a press release.

Jelly genius

Hydrogel is a material produced by carefully removing the liquids from a jelly, leaving a porous structure that has advantages such as resistance to extreme heat.

The 3D hydrogel developed by IISc scientists is made of collagen, a key molecule present in the ECM of lung cells. Collagen is soluble in water at a slightly acidic pH. As the pH increases, the collagen forms fibrils which cross-link to form a gel-like 3D structure. At the time of gelling, the researchers added human macrophages (immune cells involved in fighting infection) along with the tuberculosis causing pathogen. This entrapped both the macrophages and the bacteria in the collagen allowing researchers to track how the microbe infects the macrophages, the IISc write-up says. Using this set up, the team tracked the progress of an infection over 2-3 weeks. They found that the mammalian cells stayed viable for three weeks. Contrast this with just about a week when they did it by conventional culture methods. Further, the researchers carried out RNS sequencing of the lung cells that grew in hydrogel. They found that the cells were very similar to actual human samples.

The team also tested the effect of pyrazinamide — one of the four most common drugs given to TB patients. They found that even a small amount (10 µg/ml) of the drug was quite effective in clearing out the TB pathogen in the hydrogel culture, says IISc.

Previously, scientists have had to use large doses of the drug — much higher compared to concentrations achieved in patients — to show that it is effective in tissue culture. “Nobody has shown that this drug works in clinically relevant doses in any culture systems… Our setup reinforces the fact that the 3D hydrogel mimics the infection better,” observes Rachit Agarwal.

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Conquering the skies with flying taxis

by Hansraj Agrawal | Jul 14, 2024 | Science

It’s a common sight to see small size drones with a carrying capacity of 5 to 10 kg in the sky spraying pesticides, or involved in surveillance of critical infrastructure or delivering drugs in to remote areas. But, the IIT Madras-incubated ePlane is trying to disrupt the sector with its eVTOLs (electric Vertical Take-off and Landing) — an electric drone that can carry both cargo and passengers. The 3X3 m sized muti-copter drone can carry 35 to 50 kg of cargo, travel at 400 ft and up to 50 km.

ePlane, which got a funding of $5-million for the project, is building India’s first and the world’s most compact flying electric taxi with a vision to make flying ubiquitous, says Satyanarayanan R Chakravarthy, Professor, Department of Aerospace Engineering, IIT-Madras, and Founder Director of ePlane.

If a car takes an hour to reach a destination, or a helicopter 27 minutes, eVTOL will take just 14 minutes, claims the ePlane team.

eVTOL will serve short haul mobility and urban mobility where there is a traffic congestion problem, says Prof Satyanarayanan, adding that electric aviation will disrupt the aviation sector in the foreseeable future.

From India, for the world

“What is good for India is good for the world. India should do it ahead of others. The country has UPI; the Aadhar stack and EVMs, then why not electric aviation,” he asks.

The five-year-old deep-tech start-up has developed a subscale prototype which it demonstrated last year. It is now working on a commercial version. “We are on the verge of flying that in the next few weeks, and then we will commercialise it. The subscale version is not meant for passenger travel but for cargo. We will tap the logistics players to adopt it. We have to go through a certification process for that as well,” he says.

“We are working on the passenger version, getting into the detailed design phase now. We will get into prototyping later this year. By early next year, we should have the first passenger prototype,” says Prof Satyanarayanan.

The company has built autonomous flight paths for collision avoidance. It will also set up autonomous Air Traffic Control with manual override for safe landing at various locations, he noted.

The subscale prototype will be governed by the drone rules. Although it can go at high altitudes of around 5,000 ft, it can be flown under 400 ft as well. There may not be much hindrance in India as most of the buildings are 50 m to 100 m tall, he explained.

The 50 kg payload could be the mid-mile segment for clients like logistics players and parcel delivering companies. “We are not going to replace all of the cargo movement. We feel that precious cargo, time critical cargo, medical supplies and organs between hospitals are a few examples where we can come in,” he said.

Spreading wings

Drone is a competitive space with different players deploying drones of different sizes and varieties. However, eVTOL flies with wings to cover longer distances. The key is to test the commercial prototype. “We are a few weeks away from its flight test of at least 100 hours. Then we will go through the certification process. We are a few months away from commercialisation,” he added.

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The future of robotics lies in our DNA

by Hansraj Agrawal | Jul 8, 2024 | Science

One doesn’t have to study DNA to only study genetics; Scientists are using its programmable nature to create autonomous molecular systems with robotic abilities. In a recent study, “Autonomous assembly and disassembly of gliding molecular robots regulated by a DNA-based molecular controller”, Ibuki Kawamata et al demonstrated how DNA can control molecular-level robots.

This is a significant step toward the future of bio-inspired robotics, with applications in medicine, environmental monitoring and nanotechnology. This research brings us closer to the reality of tiny robots — smaller than a human cell — carrying out complex tasks without human intervention.

Bio-inspired robotics

Living organisms exhibit remarkable autonomy, sensing and responding to their environment without external guidance. Inspired by this efficiency, researchers have been attempting to replicate such behaviour in artificial systems. Enter bio-inspired robotics, blending biology with engineering to create robots from biological molecules. These molecular robots, made from DNA and proteins, are designed to operate at the nanoscale, performing precise tasks within biological environments.

The researchers wanted to develop a system in which molecular robots could self-assemble and disassemble without external prompts. The molecular robots are a combination of a DNA-based molecular controller (specific DNA complexes and enzymes), microtubule (protein) structures and kinesin (protein) motors. These robots were programmed to autonomously form and break apart structures, mimicking natural cellular behaviours.

The molecular controller is designed to generate two different DNA strands that serve as assembly and disassembly signals for the DNA-functionalised microtubules. These DNA signals are designed to trigger specific interactions between the microtubules, leading to their assembly into bundle-like structures or disassembly into individual filaments.

The DNA controller operates through a series of strand displacement and enzymatic reactions. By carefully designing the DNA sequences and reaction cascades, the controller can autonomously perform three basic steps: signal synthesis, release of the linker, and dissociator synthesis.

Seeing is Believing

The researchers analysed the images of the performance by the fluorescent markers of the microtubules using Differential Dynamic Microscopy (DDM). This helped them understand the dynamics of the assembly and disassembly, ensuring that the system functioned as intended.

The DNA controller successfully programmed the microtubules to autonomously assemble into bundle-like structures and then disassemble into individual filaments. This autonomous behaviour was achieved without any external interference, demonstrating the controller’s effectiveness. The system maintained its autonomous function over a significant period, crucial for practical applications, ensuring that the molecular robots can perform their tasks reliably over time.

The Big Picture

The development of autonomous molecular robots is a significant leap forward in synthetic biology and robotics. These tiny machines offer unprecedented precision and control at the molecular level, opening new avenues for scientific and technological advancements.

Molecular robots can revolutionise drug delivery in healthcare and medicine. These tiny machines could be designed to deliver drugs directly to diseased cells, minimising side effects and improving treatment efficacy. By targeting specific cells, such as cancer cells, molecular robots could enhance the precision and effectiveness of treatments. Autonomous molecular robots can detect and respond to environmental pollutants and initiating clean-up processes.

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Fraunhofer’s semiconducting glass generates hydrogen from sunlight

by Hansraj Agrawal | Jul 8, 2024 | Science

While the concept of using sunlight to split water to produce hydrogen (and oxygen) without the interface of electricity (called photoelectrochemical process) is not entirely new, the German Fraunhofer Institute has come up with its own design, which uses semiconductors. Researchers from the institute have collaborated to create a modular solution that enables highly flexible hydrogen generation and supply solar energy for it.

At the heart of this technology is a tandem PEC module. It’s similar to its traditional photovoltaic counterpart, but with one crucial difference: the electricity is not generated for purposes of later electrolysis elsewhere. The entire process takes place in one unit. Caution is needed throughout — since the process results in hydrogen and oxygen, the structure must be designed to maintain a strict separation between the two elements during generation and after.

“To produce the tandem cell, experts coated standard commercially available float or plate glass with semiconducting materials on both sides,” notes a press release from the institute. When the sunlight hits the glass, one side of the module absorbs the short-wavelength light. Meanwhile, the long-wavelength light passes through the upper layer of glass and is absorbed on the reverse side. The module releases hydrogen on the reverse or cathode side and oxygen on the upper/anode side.

Over the project’s three-year term, the Fraunhofer scientists researched and developed high-purity semiconductor materials, which they apply using ultra-gentle coating methods. This allows them to increase the method’s hydrogen yield.

“We use the vapour phase to form layers that are just a few nanometres thick on the glass. The structures created in the process have a huge impact on reactor activity, in addition to the actual material properties, which we have also optimised,” explains Dr Arno Görne, group manager of Functional Materials for Hybrid Microsystems at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS. The photovoltaic elements linked in the module supply the system with additional voltage — that accelerates activity and boosts efficiency.

The result is a reactor with an active surface area of half a square metre. Separated from the oxygen, it generates hydrogen, which can be captured and quantified. Right now, a single module exposed to sunlight under European conditions can generate over 30 kilograms of hydrogen per year over 100 square metres.

“In terms of the dimensions of the tandem cell, we are limited by the fact that our module splits water directly. But it is also necessary for electricity to get from one side to the other to achieve this. As the module area increases, the rising resistance has an unfavourable effect on the system. Currently, the existing format has proven to be optimal. It is stable, robust and significantly larger than any comparable solution,” Görne notes. The compact elements can be connected as needed without any negative side effects, from a single module to large areas – a significant advantage, the release says.

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Ionic latch against cancer

by Hansraj Agrawal | Jul 7, 2024 | Science

Researchers at IISER, Kolkata, have discovered how a cell surface receptor, part of a group of enzymes that interact with growth factors to control cell functions like growth, survival and movement, can help prevent cancers.

This receptor, called VEGFR1, remains inactive when it doesn’t have a ligand (a molecule that binds to it, like a hormone). Cell surface receptors, like Receptor Tyrosine Kinases (RTKs), are crucial for converting signals from outside the cell (like growth factors) into responses within the cell. When a ligand binds to these receptors, it activates enzymes inside the cell, which then add phosphate groups to other molecules, helping to regulate various cell functions such as growth and immune response. When RTKs activate on their own, without ligands, it can cause diseases like cancer, diabetes and autoimmune disorders. Researchers are studying how cells keep these enzymes inactive and what causes them to become active in diseases.

Dr Rahul Das of IISER, Kolkata, studied VEGFR, a receptor that regulates blood vessel formation, wound healing and tumour growth. They noticed that its two receptors, VEGFR1 and VEGFR2, act differently. VEGFR2 can activate on its own, but VEGFR1 cannot, even when there is a lot of it in cells. VEGFR1 binds more strongly to its ligand, VEGF-A, than VEGFR2 does, but this binding only briefly activates VEGFR1.

Activation of VEGFR1 was found to be linked to cancer-related pain and the survival and movement of cancer cells. Das has discovered a unique “ionic latch” in VEGFR1 which keeps it inactive by holding part of the receptor in place. By studying this inactive state, researchers proposed that a cell enzyme called tyrosine phosphatase plays a key role in regulating VEGFR1 activity. Their research suggests that targeting this mechanism could help treat diseases where new blood vessels form abnormally, like in cancer.

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MAB for hydrogen storage

by Hansraj Agrawal | Jul 7, 2024 | Science

Researchers at IIT-Madras have synthesised a tough, ceramic material that can conduct electricity and heat, which could possibly be used for storing hydrogen too.

A crystal structure found in certain materials called ‘MAB Phase’ gives them special properties such as high strength. In this M stands for a transition metal, like zirconium, molybdenum or titanium; A for either aluminium or silicon; and B for Boron.

Prof Somnath Bhattacharyya of the Department of Metallurgical and Materials Engineering and his team have developed a MAB phase layered ceramic — using tungsten, aluminium and boron — called WAlB. While WAlB is not a new material, known to be useful in nuclear shielding, Bhattacharyya and his team have developed a new process for making it, in a medium of molten salt. The resultant material is also of very high purity — about 98 per cent.

Bhattacharyya explained to Quantum that the material is a layered ceramic, with 2D layers of tungsten and boron, with aluminium in between. WAlB has been synthesised earlier at temperatures of 1400o C, but Bhattacharyya could do it at 800oC, at ambient pressure.

Calling the work a “breakthrough”, Dr Varun Natu, scientist at National Chemical Laboratory, Pune, observes that synthesising WAlB has traditionally proven difficult, resulting in only small crystals with low yield. However, “Bhattacharyya’s team has demonstrated not only large-scale synthesis of WAlB but also a method that uses a molten salt as a sheath. This approach significantly reduces production costs and simplifies potential future scaling, making WAlB a much more viable candidate for real-world applications.”

This material could be used as a semiconductor or for hydrogen storage, he said. Asked if the industry could take up production of this MAB at scale, Bhattacharyya said it was possible, as repeated synthesis by his students got the same, high purity material.

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