Passive human structures like roads and settlements sometimes reduced animal vigilance, an Indian Institute of Science release said. File
| Photo Credit: The Hindu

Cells navigating through a tissue-like environment showing diverse shapes and morphologies.
| Photo Credit: special arrangement

A new study from the Indian Institute of Science (IISc) shows how inherent variations in a cancer cell and its interactions with its surroundings mould its migration.

The findings, published in Biophysical Journal, reveal that cancer cells seem to adapt their migratory pattern depending on the physical and biochemical characteristics of their surroundings, called the microenvironment.

“The spread of tumour from the primary cancer site to distant organs, called metastasis, has puzzled scientists for many years – they are only now beginning to pinpoint triggers and mechanisms that drive this process,” IISc said.

How they adapt

The researchers studied two types of ovarian cancer cells – OVCAR-3, which has a well-structured polygonal shape, and SK-OV-3, which has a naturally elongated spindle shape. Both of these cells metastasise and invade tissues. By placing these cells on soft and stiff surfaces that mimic healthy and diseased tissues, the researchers observed how each type adapted its movement on different surfaces.

On soft surfaces, similar to healthy tissue, both cell types moved slowly in random directions. But on stiff surfaces, which mimic the tough, scarred tissue around tumours, the cells are more deformable and respond differently.

“Based on previous literature, I expected stiffness to be an important factor in aggravating cancer cell migration. However, what I did not expect was that the epithelioid ovarian cancer cells (OVCAR-3) were more migratory than the mesenchymal cells (SK-OV-3) on stiffer matrices,” said Madumitha Suresh, former MTech student at the Department of Bioengineering (BE) and first author of the study.

Shape matters

The researchers also observed a unique movement pattern in the OVCAR-3 cells, which they called slip. In most cells, the direction of movement aligns with the shape of the cell, with the cell’s front leading the way. But when the OVCAR-3 cells moved on stiff surfaces, this alignment broke down.

“Their movement became less coordinated with their shape, almost as if they were sliding or slipping instead of moving in a straight line. Motivated by these unexpected results, the researchers sought to understand the process using quantitative approaches,” IISc said.

It added that existing methods for studying how cancer cells move are either mathematical approaches that don’t capture changes over time or complex computer-based approaches, such as machine learning, that are challenging to use.

Collective dynamics

“We aim to extend our study to decipher the collective dynamics of such cancer cells, especially in more complex 3D environments. This will shed fresh light on the pathology of ovarian cancer, a disease that is characterised by rapid metastasis and high morbidity,” said Ramray Bhat, associate professor at the Department of Developmental Biology and Genetics and corresponding author of the study.

Cells navigating through a tissue-like environment showing diverse shapes and morphologies.
| Photo Credit: special arrangement

A new study from the Indian Institute of Science (IISc) shows how inherent variations in a cancer cell and its interactions with its surroundings mould its migration.

The findings, published in Biophysical Journal, reveal that cancer cells seem to adapt their migratory pattern depending on the physical and biochemical characteristics of their surroundings, called the microenvironment.

“The spread of tumour from the primary cancer site to distant organs, called metastasis, has puzzled scientists for many years – they are only now beginning to pinpoint triggers and mechanisms that drive this process,” IISc said.

How they adapt

The researchers studied two types of ovarian cancer cells – OVCAR-3, which has a well-structured polygonal shape, and SK-OV-3, which has a naturally elongated spindle shape. Both of these cells metastasise and invade tissues. By placing these cells on soft and stiff surfaces that mimic healthy and diseased tissues, the researchers observed how each type adapted its movement on different surfaces.

On soft surfaces, similar to healthy tissue, both cell types moved slowly in random directions. But on stiff surfaces, which mimic the tough, scarred tissue around tumours, the cells are more deformable and respond differently.

“Based on previous literature, I expected stiffness to be an important factor in aggravating cancer cell migration. However, what I did not expect was that the epithelioid ovarian cancer cells (OVCAR-3) were more migratory than the mesenchymal cells (SK-OV-3) on stiffer matrices,” said Madumitha Suresh, former MTech student at the Department of Bioengineering (BE) and first author of the study.

Shape matters

The researchers also observed a unique movement pattern in the OVCAR-3 cells, which they called slip. In most cells, the direction of movement aligns with the shape of the cell, with the cell’s front leading the way. But when the OVCAR-3 cells moved on stiff surfaces, this alignment broke down.

“Their movement became less coordinated with their shape, almost as if they were sliding or slipping instead of moving in a straight line. Motivated by these unexpected results, the researchers sought to understand the process using quantitative approaches,” IISc said.

It added that existing methods for studying how cancer cells move are either mathematical approaches that don’t capture changes over time or complex computer-based approaches, such as machine learning, that are challenging to use.

Collective dynamics

“We aim to extend our study to decipher the collective dynamics of such cancer cells, especially in more complex 3D environments. This will shed fresh light on the pathology of ovarian cancer, a disease that is characterised by rapid metastasis and high morbidity,” said Ramray Bhat, associate professor at the Department of Developmental Biology and Genetics and corresponding author of the study.

Indian Institute of Science in Bengaluru
| Photo Credit: SUDHAKARA JAIN

The Headquarter Maintenance Command of the Indian Air Force (IAF) has entered into a Memorandum of Agreement (MoA) with Indian Institute of Science (IISc.) and Foundation for Science Innovation and Development (FSID), Bengaluru on November 18.

The MoA includes jointly identifying problem areas of IAF in maintenance and servicing of equipment related to radar, aircraft, IT and communication platforms and developing a strategic road map for reliability-centered maintenance through Research and Development.

This will also include Artificial Intelligence (AI), Machine Learning (ML), Digital Twin based technologies for lifecycle management, productive maintenance and asset planning.

The Ministry of Defence expects the MoA to enable the two organisations to access testing facilities available with each other for mutual benefit. It will also enable IAF in enhancing academic interaction with IISc towards Post Graduate Programs and support in collaborative R&D efforts. This collaboration will give a boost to self-reliance under Atmanirbhar Bharat, and encourage startups, MSME and other industrial setups to participate in defence indigenisation programs.

The Indian Institute of Science team used a 2D material to design what they call a non-linear optical mirror stack to increase or up-convert the frequency of short infrared light to the visible range, combined with widefield imaging capability.
| Photo Credit: File Photo

Researchers at the Indian Institute of Science (IISc) have fabricated a device to increase or up-convert the frequency of short infrared light to the visible range. This up-conversion of light has diverse applications, especially in defence and optical communications, said IISc.

“The human eye can only see light at certain frequencies (called the visible spectrum), the lowest of which constitutes red light. Infrared light, which we can’t see, has an even lower frequency than red light. IISc researchers have now fabricated a device to increase or up-convert the frequency of short infrared light to the visible range,” IISc said.

2D material used

The institute added that in a first, the IISc team used a 2D material to design what they call a non-linear optical mirror stack to achieve this up-conversion, combined with widefield imaging capability. The stack consists of multilayered gallium selenide fixed to the top of a gold reflective surface, with a silicon dioxide layer sandwiched in between.

It said that traditional infrared imaging uses exotic low-energy bandgap semiconductors or micro-bolometer arrays, which usually pick up heat or absorption signatures from the object being studied.

However, existing infrared sensors are bulky and not very efficient. They are also export-restricted because of their utility in defence. There is, therefore, a critical need to develop indigenous and efficient devices.

The method used by the IISc team involves feeding an input infrared signal along with a pump beam onto the mirror stack. The nonlinear optical properties of the material constituting the stack result in a mixing of the frequencies, leading to an output beam of increased (up-converted) frequency, but with the rest of the properties intact. Using this method, they were able to up-convert infrared light of a wavelength of around 1,550 nm to 622 nm visible light. The output light wave can be detected using traditional silicon-based cameras.

Going forward, the researchers plan to extend their work to up-convert light of longer wavelengths. They are also trying to improve the efficiency of the device by exploring other stack geometries.

Worldwide interest

“There is a lot of interest worldwide in doing infrared imaging without using infrared sensors. Our work could be a game-changer for those applications,” said Varun Raghunathan, associate professor, Department of Electrical Communication Engineering.

Indian Institute of Science, Bengaluru

Researchers at the Department of Biochemistry, Indian Institute of Science, have developed a novel method for the production of recombinant proteins.

According to IISc, mass production of recombinant proteins using yeast cell factories needs methanol, a compound that requires safe handling, carries the risk of catching fire, and sometimes produces harmful byproducts. However, researchers have now developed an alternative, safer process that instead relies on a common food additive called monosodium glutamate (MSG).

Recombinant proteins, such as vaccine antigens, insulin and monoclonal antibodies, are mass-produced by growing modified bacterial, viral or mammalian cells in large bioreactors. The most widely used organism is the yeast Pichia pastoris (now called Komagataella phaffii).

A unique promoter

“It contains a unique promoter – a specific gene region which can be activated by methanol. This promoter codes for an enzyme called alcohol oxidase (AOX),” IISc said.

To mass-produce a recombinant protein, the gene coding for that protein is spliced into the yeast genome right next to the AOX promoter. The yeast cells are then fed glycerol or glucose as the carbon source. Once enough cells have formed, methanol is added, which activates the AOX promoter, and the cells start producing the recombinant protein in copious amounts.

“Most industries use this methanol-induced process for producing recombinant proteins. However, methanol is highly flammable and hazardous, requiring stringent safety precautions. Methanol is also metabolized to form hydrogen peroxide which can induce oxidative stress in the yeast cells or damage the recombinant proteins,” said Prof P.N. Rangarajan, corresponding author of the study published in Microbial Cell Factories.

Role of MSG

To solve this problem, Trishna Dey, a former PhD student at the Department of Biochemistry, started looking for alternatives. After an extensive search, the team found that monosodium glutamate (MSG), a USFDA-approved food additive, can activate a different promoter in the yeast genome that codes for an enzyme called phosphoenolpyruvate carboxykinase (PEPCK). Activating this promoter with MSG led to protein production similar to methanol activation of the AOX promoter.

The researchers hope that this novel and indigenous expression system can be used in biotech industries to mass-produce valuable proteins, including milk and egg proteins, baby food supplements, and nutraceuticals, as well as therapeutic molecules.

A portable fluorescence reader device. Researchers at the Indian Institute of Science (IISc.) and Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) have developed a paper-based platform which could help quickly detect the presence of antibiotic-resistant, disease-causing bacteria.
| Photo Credit: Special Arrangement

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

According to the World Health Organisation (WHO), 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. Hence, timely diagnosis can improve the efficiency of treatment.

“Generally, the doctor diagnoses the patient and gives them medicines. The patient then takes it for two to three 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,” said Uday Maitra, Professor in the Department of Organic Chemistry, IISc.

In a paper published in ACS Sensors, Prof. 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.

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). When scrutinised by UV light, this hydrogel emits green fluorescence.

The team also collaborated with Adiuvo Diagnostics, a Tamil Nadu-based company, 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. A dedicated software app measures the intensity, which can help quantify the bacterial load.

The team from IISc tied up with Jayanta Haldar’s research group from JNCASR to check their approach on urine samples.

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

The Indian Institute of Science, Bengaluru

An interdisciplinary team of researchers from the Indian Institute of Science have uncovered how the stiffness of a cell’s microenvironment influences its form and function. The findings are expected to provide a better understanding of what happens to tissues during healing of wounds.

Scar formation

“Inefficient wound healing results in tissue fibrosis, a process that can cause scar formation and may even lead to conditions like cardiac arrest. Changes in the mechanical properties of tissues like stiffness also happen in diseases like cancer,” IISc said.

The research team was led by Prof. Namrata Gundiah from the Department of Mechanical Engineering and Prof. Paturu Kondaiah from the Department of Developmental Biology and Genetics.

Change in stiffness

In the study, published in Bioengineering, the team cultured fibroblast cells, the building blocks of our body’s connective tissue, on a polymer substrate called PDMS with varying degrees of stiffness.

They found that a change in the stiffness altered the cell structure and function. Fibroblast cells are involved in extensive remodelling of the extracellular matrix (ECM) surrounding biological cells.

The ECM, in turn, provides the mechanical tension that cells feel inside the body. The team found that fibroblasts cultured on substrates that had lower stiffness were rounder and showed accompanying changes in the levels of cytoskeleton proteins such as actin and tubulin. Moreover, fibroblasts grown on such substrates showed cell cycle arrest, lower rates of cell growth and cell death.

Regulator that drives changes

To pinpoint the master regulator that drives changes in the cell when substrate stiffness changes, the team focused their attention on an important signalling protein called Transforming Growth Factor-β (TGF-β). Previous work has shown that the activity of fibroblasts and the downstream ECM architecture is regulated by TGF-β.

“The thing is, people talk about the chemical changes but not about biomechanical changes. For example, while the TGF-β signalling cascade has been studied extensively in cancer, the influence of mechanical forces such as substrate stiffness has not been studied so far,” said Brijesh Kumar Verma, first author of the study. In the future, the researchers seek to understand how other mechanical factors, such as surface properties and cell stretch, can also influence TGF-β activity.