11 July 2023

– Soumya Mishra

Scientists at the Department of Materials Engineering, Indian Institute of Science (IISc), have developed a super flexible, composite semiconductor material that can have possible applications in next-generation flexible or curved displays, foldable phones and wearable electronics.

Traditional semiconductor devices – such as transistors, the building blocks of most electronic circuits – used in display industries are either made of amorphous silicon or amorphous oxides, both of which are not flexible and strain tolerant at all. Adding polymers to the oxide semiconductors may increase their flexibility, but there is a limit to how much can be added without compromising the semiconductor’s performance.

In the current study, published in Advanced Materials Technologies, the researchers have found a way to fabricate a composite containing a significant amount of polymer – up to 40% of the material weight – using a solution-process technique, specifically inkjet printing. In contrast, previous studies have reported only up to 1-2% polymer addition. Interestingly, the approach enabled the semiconducting properties of the oxide semiconductor to remain unaltered with the polymer addition. The added large quantity of polymer also made the composite semiconductor highly flexible and foldable without deteriorating its performance.

The composite semiconductor is made up of two materials – a water-insoluble polymer such as ethyl cellulose that provides flexibility, and indium oxide, a semiconductor which brings in excellent electronic transport properties. To design the material, the researchers mixed the polymer with the oxide precursor in such a way that interconnected oxide nanoparticle channels are formed (around phase-separated polymer islands) through which electrons can move from one end of a transistor (source) to the other (drain), ensuring a steady current flow. The key to form these connected pathways, the researchers found, was the choice of the right kind of water-insoluble polymer that does not mix with the oxide lattice when the oxide semiconductor is being fabricated. “This ‘phase separation’ and the formation of polymer-rich islands helps in crack arrest, making it super flexible,” says Subho Dasgupta, Associate Professor in the Department of Materials Engineering, and corresponding author of the study.

The composite semiconductor-based transistors on flexible Kapton substrate and envisioned fully printed flexible display (Image: Jyoti Ranjan Pradhan)

Semiconductor materials are usually fabricated using deposition techniques such as sputtering. Instead, Dasgupta’s team uses inkjet printing to deposit their material onto various flexible substrates ranging from plastics to paper. In the present study, a polymer material called Kapton has been used. Just like words and images printed on paper, electronic components can be printed on any surface using special functional inks containing either electrically conducting, semiconducting or insulating materials. However, there are challenges. “Sometimes it is very difficult to get a continuous and homogeneous film. Therefore, we had to optimise certain protocols, for example, preheating the printed semiconductor layer on the Kapton substrate prior to high temperature annealing,” explains first author Mitta Divya, former PhD student at the Department of Materials Engineering and currently a postdoc at King Abdullah University of Science and Technology (KAUST), Saudi Arabia. Another challenge is ensuring the right environmental conditions under which the ink can be printed. “If the humidity is too low, you can’t print, because the ink dries up within the nozzle,” says Subho Dasgupta.

He adds that in the future, such printed semiconductors can be used to fabricate fully printed and flexible television screens, wearables, and large electronic billboards alongside printed organic light emitting diode (OLED) display front-ends. These printed semiconductors will be low-cost and easy to manufacture, which could potentially revolutionise the display industry. His team has obtained a patent for their material and plans to test its shelf-life and quality control from device to device before it can be scaled up for mass production. They also plan to look for other polymers that can help design such flexible semiconductors.

REFERENCE:
Divya M, Cherukupally N, Gogoi SK, Pradhan JR, Mondal SK, Jain M, Senyshyn A, Dasgupta S, Super Flexible and High Mobility Inorganic/Organic Composite Semiconductors for Printed Electronics on Polymer Substrates, Advanced Materials Technologies (2023).

CONTACT:
Subho Dasgupta
Associate Professor
Department of Materials Engineering
Indian Institute of Science (IISc)
Email: dasgupta@iisc.ac.in
Phone: +91-80-2293 2455
Website: https://materials.iisc.ac.in/~dasgupta/index.html

Mitta Divya
Former IISc PhD student
Post-Doctoral Researcher
IMPACT Lab, CEMSE Division
King Abdullah University of Science and Technology (KAUST), Saudi Arabia
Email: divya.mitta@kaust.edu.sa

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.

18 July 2023

– Malavika P Pillai

Picolinic acid, a natural compound produced by mammalian cells, can block several disease-causing viruses such as SARS-CoV-2 and influenza A viruses, according to a new study by researchers at the Indian Institute of Science (IISc) and collaborators.

Published in Cell Reports Medicine, the study describes the compound’s remarkable ability to disrupt the entry of enveloped viruses into the host’s cell and prevent infection. The team hopes to develop the compound into a broad-spectrum therapeutic that can help fight against a variety of viral diseases.

Picolinic acid is known to help in the absorption of zinc and other trace elements from our gut, but in its natural form, it stays inside the body only for a short duration and is usually excreted out quickly. In recent years, scientists have begun noticing that it may also exhibit antiviral activity.

A few years ago, the IISc team began investigating endocytosis, a cellular process often co-opted by viruses and bacteria to enter our cells. During their investigations, the researchers stumbled upon picolinic acid and realised that the compound could slow down viral entry into host cells. Therefore, they decided to test the compound’s antiviral potential. “Coincidentally, the pandemic emerged during the study. So, we extended our research to examine its impact on SARS-CoV-2 and found it to be even more potent in this context,” explains corresponding author Shashank Tripathi, Assistant Professor at the Department of Microbiology and Cell Biology (MCB) as well as the Centre for Infectious Diseases Research (CIDR), IISc.

Notably, picolinic acid displayed a preference for blocking enveloped viruses. In addition to the usual protein coat found in all viruses, these enveloped viruses also have an extra outer membrane made of lipids derived from the host. This envelope is crucial for virus entry into its target cell. Incidentally, a majority of human viruses with high prevalence and pandemic potential are enveloped viruses.

During their entry into host cells, the virus envelope and the host cell membrane fuse, creating a pore through which the virus’s genetic material enters the host cell and starts replicating. The researchers found that picolinic acid specifically blocks this fusion, which explains its effectiveness against a variety of enveloped viruses, including flaviviruses like the Zika virus and the Japanese encephalitis virus. The compound did not have much effect on non-enveloped viruses like rotavirus and coxsackievirus.

Picolinic acid is a broad-spectrum antiviral (Image: Rajesh Yadav)

Usually, antiviral drugs target either the virus directly – which can sometimes lead to drug resistance – or some part of the host cell – which may lead to negative side-effects. “This compound, on the contrary, stands out because it falls in between … it is targeting a host-derived component of the virus,” explains Tripathi. “Since the viruses borrow this component from the host, they don’t have the machinery to repair the damage to their envelope. So, with the same compound, you are damaging the virus permanently, while causing very transient minimal effect on the host cell with self-repair ability.”

When the compound was tested in SARS-CoV-2 and influenza animal models, it was found to protect the animals from infection. It was also found to reduce viral load in the lungs when given to infected animals. In addition, the researchers found that picolinic acid led to an increase in the number of immune cells in the animals.

Rohan Narayan, Research Associate in CIDR and first author of the paper, says, “Our current focus is on enhancing the compound’s efficacy, stability and absorption in the host body. We are seeking partnerships with pharmaceutical industries to facilitate its clinical development and use against present as well as impending viral outbreaks.”

REFERENCE:

Narayan R, Sharma M, Yadav R, Biji A, Khatun O, Kaur S, Kanojia A, Joy CM, Rajmani R, Sharma PR, Jeyasankar S, Rani P, Shandil RK, Narayanan S, Rao DC, Satchidanandam V, Das S, Agarwal R, Tripathi S, Picolinic acid is a broad-spectrum inhibitor of enveloped virus entry that restricts SARS-CoV-2 and influenza A virus in vivo, Cell Reports Medicine (2023).

CONTACT:

Rohan Narayan
Research Associate
Centre for Infectious Diseases Research (CIDR)
Indian Institute of Science (IISc)
Email: rohannarayan@iisc.ac.in

Shashank Tripathi
Assistant Professor
Department of Microbiology and Cell Biology (MCB)
Centre for Infectious Disease Research (CIDR)
Indian Institute of Science (IISc)
Email: shashankt@iisc.ac.in
Phone: +91-22932884
Website: https://cidr.iisc.ac.in/shashank/

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.

20 July 2023

– Ranjini Raghunath

Researchers at the Indian Institute of Science (IISc) have designed a short peptide capable of poisoning a key enzyme in disease-causing bacteria, including some of most deadly and antibiotic-resistant species.

Made from a short stretch of about 24 amino acids, the peptide mimics the action of a natural toxin which inhibits a class of enzymes called topoisomerases. These enzymes play a crucial role in unspooling and re-coiling bacterial DNA during replication and protein synthesis. They are an attractive target for antibiotics because the ones in bacteria are very different from those in humans.

Among the most widely used antibiotics are fluoroquinolones such as ciprofloxacin, which target these topoisomerases. However, overuse of these antibiotics around the world has led to the alarming rise of antibiotic-resistant bacteria, prompting scientists to pursue alternative strategies and molecules.

Topoisomerases form a covalent adduct – an intermediate complex – with the bacterial DNA, to coil or uncoil it. The peptide developed by the IISc team binds to this adduct and “traps” it in place, kicking off a cascade of events that lead to cell death, explains Raghavan Varadarajan, Professor at the Molecular Biophysics Unit (MBU), and one of the corresponding authors of the study published in EMBO Reports. This is similar to how a natural toxin called CcdB, produced by certain other bacteria and plasmids, works.

“The full length CcdB protein is large. It is not feasible to use it as a drug in its entirety,” says first author Jayantika Bhowmick, former PhD student at MBU and currently a postdoctoral researcher at the University of Cambridge. Instead, the team snipped out a small stretch from the tail end of this protein and added a few more amino acids that would allow the new peptide to enter bacterial cells. The peptide design was carried out by the lab of Jayanta Chatterjee, Professor in MBU.

Image: Jayantika Bhowmick

The team then tested the new peptide’s effect on the growth of several disease-causing bacterial species, including E. coli, Salmonella Typhimurium, Staphylococcus aureus and a multidrug resistant strain of Acinetobacter baumanii – both in cell culture as well as animal models, in collaboration with the lab of Dipshikha Chakravortty, Professor at the Department of Microbiology and Cell Biology (MCB). They also compared the effect of their peptide against clinical doses of ciprofloxacin. Depending on the species, the peptide was found to either block or “poison” a specific type of topoisomerase – an enzyme called DNA gyrase in many of them, explains Manish Nag, PhD student at MBU and another author. “It is [also] capable of disrupting most of the strains’ membranes,” he adds.

In animal models, the peptide was found to drastically reduce infection. “In most of the cases, we saw that the decline in the bacterial count in major organs following peptide treatment was higher than in the ciprofloxacin-treated group. That was pretty encouraging to us,” says Bhowmick. For example, in animals infected with antibiotic-resistant Acinetabacter baumannii, the peptide treatment caused an 18-fold reduction in bacterial load in the liver, compared to only a 3-fold reduction by ciprofloxacin. The peptide was also found to be relatively safe and did not cause toxic reactions in the animals.

Since the peptide binds to a different site on the bacterial enzyme than ciprofloxacin, the researchers believe that it provides leads for identification of drugs that can be used as a combination therapy with existing antibiotics. Varadarajan adds that the study also reinforces the importance of targeting topoisomerases as a valid approach to finding new antibiotics.

REFERENCE:

Bhowmick J, Nag M, Ghosh P, Rajmani RS, Chatterjee R, Karmakar K, Chandra K, Chatterjee J, Chakravortty D, Varadarajan R, A CcdB toxin-derived peptide acts as a broad-spectrum antibacterial therapeutic in infected mice, EMBO Reports (2023).

CONTACT:

Jayantika Bhowmick
Postdoctoral researcher, University of Cambridge
Former PhD student, Molecular Biophysics Unit, Indian Institute of Science (IISc)
Email: jay18nov@gmail.com

Manish Nag
PhD student
Molecular Biophysics Unit, Indian Institute of Science (IISc)
Email: manishnag@iisc.ac.in

Raghavan Varadarajan
Professor
Molecular Biophysics Unit, Indian Institute of Science (IISc)
Email: varadar@iisc.ac.in
Phone: +91-80-22932612
Website: http://mbu.iisc.ac.in/~rvgrp/home.html

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.

27 July 2023

– Sandeep Menon

High up in the Himalayas, scientists at the Indian Institute of Science (IISc) and Niigata University, Japan, have discovered droplets of water trapped in mineral deposits that were likely left behind from an ancient ocean which existed around 600 million years ago. Analysis of the deposits, which had both calcium and magnesium carbonates, also allowed the team to provide a possible explanation for events that might have led to a major oxygenation event in Earth’s history.

“We have found a time capsule for paleo oceans,” says Prakash Chandra Arya, PhD student at the Centre for Earth Sciences (CEaS), IISc, and first author of the study published in Precambrian Research.

Top: Field exposures of magnesite near Chandak hills, Kumaon. Bottom: Microphotographs of ocean water trapped in magnesite crystals (Photos: Prakash Chandra Arya)

Scientists believe that between 700 and 500 million years ago, thick sheets of ice covered the Earth for an extended period, called the Snowball Earth glaciation (one of the major glacial events in Earth’s history). What followed this was an increase in the amount of oxygen in the Earth’s atmosphere, called the Second Great Oxygenation Event, which eventually led to the evolution of complex life forms. So far, scientists have not fully understood how these events were connected due to the lack of well-preserved fossils and the disappearance of all past oceans that existed in the Earth’s history. Exposures of such marine rocks in the Himalayas can provide some answers.

“We don’t know much about past oceans,” says Prakash. “How different or similar were they compared to present-day oceans? Were they more acidic or basic, nutrient-rich or deficient, warm or cold, and what was their chemical and isotopic composition?” Such insights could also provide clues about the Earth’s past climate, and this information can be useful for climate modelling, he adds.

The deposits found by the team – which date back to around the time of the Snowball Earth glaciation – showed that the sedimentary basins were deprived of calcium for an extended period, probably due to low riverine input. “During this time, there was no flow in the oceans, and hence no calcium input. When there is no flow or calcium input, as more calcium precipitates, the amount of magnesium goes up,” explains Sajeev Krishnan, Professor at CEaS and corresponding author of the study. The magnesium deposits formed at this time were able to trap paleo ocean water in their pore space as they crystallised, the researchers suggest.

The calcium deprivation also likely led to a nutrient deficiency, making it conducive for slow-growing photosynthetic cyanobacteria, which could have started spewing out more oxygen into the atmosphere. “Whenever there is an increase in the oxygen level in the atmosphere, you will have biological radiation (evolution),” says Prakash.

The team hunted for these deposits across a long stretch of the western Kumaon Himalayas, extending from Amritpur to the Milam glacier, and Dehradun to the Gangotri glacier region. Using extensive laboratory analysis, they were able to confirm that the deposits are a product of precipitation from ancient ocean water, and not from other places, such as the Earth’s interior (for example, from submarine volcanic activity).

The researchers believe that these deposits can provide information about ancient oceanic conditions such as pH, chemistry, and isotopic composition, which have so far only been theorised or modelled. Such information can help answer questions related to the evolution of oceans, and even life, in Earth’s history.

REFERENCE:

Arya PC, Nambaje C, Kiran S, Satish-Kumar M, Sajeev K, Himalayan magnesite records abrupt cyanobacterial growth that plausibly triggered the Neoproterozoic Oxygenation Event, Precambrian Research (2023).

CONTACT:

Prakash Chandra Arya
PhD student, Centre for Earth Sciences (CEaS)
Indian Institute of Science (IISc)
Email: prakasha@iisc.ac.in

Sajeev Krishnan
Professor, Centre for Earth Sciences (CEaS)
Indian Institute of Science (IISc)
E-mail: sajeev@iisc.ac.in
Phone: +91-80-2293-3404
Website: https://ceas.iisc.ac.in/author/sajeev-krishnan/
Lab website: https://www.petralab.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.