- Rohini Subrahmanyam
 

Adult Russell’s viper (Photo: Kartik Sunagar)

Snake venom has evolved into a complex cocktail of chemical killers, with remarkable diversity across different snake species. Even the same snake species can face different evolutionary and ecological pressures over time, which can change the potency of its venom.

In a recent study published in BMC Biology, Kartik Sunagar, Associate Professor at the Evolutionary Venomics Lab, Center for Ecological Sciences, IISc, and collaborators explored how the evolutionary ecology of two snake species shapes their venom as they age. The team focused on two clinically relevant venomous snakes in India, the Russell’s viper (Daboia russelii) and the spectacled cobra (Naja naja) – both responsible for a distressing number of deaths and disabilities.

The researchers maintained more than 200 snakes of the two species in captivity, to source venom from them at different stages of the snakes’ lives. They then performed several experiments to check how the composition, activity, and toxicity of the venom changes over time as these snakes change their diet from feeding on one prey to another.

Russell’s viper neonate (Photo: Kartik Sunagar)

Interestingly, the toxicity of the two snakes’ venom varied based on its ontogeny – at which stage of life it was sourced from. In the Russell’s viper, newborns had considerably higher toxicity against mammals and reptiles, as compared to juveniles and adult snakes. On the other hand, the toxicity levels of the cobra venom remained the same over the course of its development. The latter could, however, bind strongly to receptors found in the cell surface of various prey animals, most likely to make up for its lack of ontogenic variation, the researchers suggest. The results provide a glimpse into the evolutionary arms race between prey and predator, and how snakes have adapted and developed effective venom concoctions.

The findings of the study can not only help us better understand how snake venom diversity may have evolved, but also aid us in developing more effective snakebite treatments, which is also a major theme of the lab.

REFERENCE:
Senji Laxme RR, Khochare S, Bhatia S, Martin G, Sunagar K, From birth to bite: the evolutionary ecology of India's medically most important snake venoms, BMC Biology (2024).

 https://doi.org/10.1186/s12915-024-01960-8

LAB WEBSITE:
https://www.venomicslab.com/

18 August 2023

–Pratibha Gopalakrishna

In a new study, researchers at the Department of Biochemistry, Indian Institute of Science (IISc), have used a novel imaging technique to pinpoint how strongly adjacent bases – the building blocks of DNA – stack up on top of each other in a single strand. The findings open up possibilities for building complex DNA nanodevices and unravelling fundamental aspects of DNA structure.

DNA bases have a natural tendency to adhere to one another, a characteristic that has been measured in the context of this study. (Credit: Ayushi Amin Dey)

Behind the seamless running of every living cell lies DNA – the hereditary vehicle carrying information for its growth, functioning and reproduction. Each DNA strand is usually made up of four nucleotide bases – Adenine (A), Guanine (G), Thymine (T) and Cytosine (C). The bases on one strand pair with those on the opposite strand to form the double-stranded DNA (A pairs with T and G pairs with C).

Two types of interactions stabilise DNA’s double helix structure. Base-pairing – interaction between bases on opposite strands – is more widely known, whereas base-stacking – interaction between bases in the same strand – is not very well studied. Imagine a zipper in which base-pairing is like the zip holding the two strands together, while base-stacking acts like the teeth of the zipper, ensuring a tight and secure connection. Base-stacking interactions are typically stronger than base-pairing, says Mahipal Ganji, Assistant Professor at the Department of Biochemistry, IISc, and corresponding author of the paper published in Nature Nanotechnology.

To study all 16 possible base-stacking combinations, the researchers used DNA-PAINT (Point Accumulation in Nanoscale Topography). DNA-PAINT is an imaging technique that works on the principle that two artificially designed DNA strands – each ending on a different base – when put together in a buffer solution at room temperature, will bind and unbind to each other randomly for a very short time. The team tagged one of the strands (imager strand) with a fluorophore that would emit light during binding and tested the stacking of this strand on top of another docked strand. The binding and unbinding of different strand combinations (based on the end bases) were captured as images under a fluorescence microscope.

Patterned DNA nanostructures (cyan) as imaged using DNA-PAINT super-resolution technique enabled for studying strength of base-stacking interactions (pink). (Credit: Abhinav Banerjee)

The time taken for the binding and unbinding of the strands was found to increase if the interaction between the stacked bases was strong, explains Abhinav Banerjee, first author and PhD student at the Department of Biochemistry. Therefore, using the data obtained from DNA-PAINT, the researchers built a model that linked the timing of binding and unbinding with the strength of interaction between the stacked bases.

Using this technique, the team was able to uncover interesting insights into base-stacking. For example, adding just one more base-stacking interaction to a DNA strand seems to increase its stability by up to 250 times. They also found that each nucleotide pair had its own unique stacking strength. This information allowed the team to design a highly efficient three-armed DNA nanostructure that could potentially be built into a polyhedron-shaped vehicle for biomedical applications, like targeting specific disease markers and delivering targeted therapies.

The researchers are also working on improving the technique of DNA-PAINT itself. Banerjee says that leveraging on stacking interactions, they plan to design novel probes which would expand the potential applications of DNA-PAINT.

Moreover, the research has broader applications beyond imaging and nanotechnology, according to the scientists. Ganji hopes that these findings can be used to study fundamental properties of single and double-stranded DNA which, in turn, may shed light on DNA repair mechanisms, the failure of which leads to many diseases including cancer.

REFERENCE:

Banerjee A, Anand M, Kalita S, Ganji M, Single-Molecule Analysis of DNA Base-Stacking Energetics Using Patterned DNA Nanostructures, Nature Nanotechnology (2023).

CONTACT:

Abhinav Banerjee
PhD student
Department of Biochemistry (BC)
Indian Institute of Science (IISc)
Email: abhinavbaner@iisc.ac.in

Mahipal Ganji
Assistant Professor
Department of Biochemistry (BC)
Indian Institute of Science (IISc)
Email: ganji@iisc.ac.in
Phone: +91 80 2293 2309
Lab website: https://ganjilab.org/

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.

11 August 2023

India’s first Agricultural Data Exchange (ADeX) was successfully launched today in Hyderabad. Developed as a digital public infrastructure (DPI) for the agriculture sector, ADeX is a collaboration between the Government of Telangana, World Economic Forum, and the Indian Institute of Science (IISc).

Hon’ble Minister for IT, Industries, and MA&UD, Shri KT Rama Rao said during the occasion, “Both ADeX and ADMF provide the right platform to ensure fair and efficient usage of agricultural data by the industry and startups and provide a big boost to the data economy specifically in the agriculture sector. These initiatives help Telangana lead the country in using innovation and technology to drive food systems transformation and improve the livelihoods of farmers.”

ADeX is an open-source, open-standard and inter-operable public good, democratising access to data and enabling the public and private sector to build applications and deliver services that benefit the society. Purushottam Kaushik, head of the Centre for the Fourth Industrial Revolution India, World Economic Forum, stated, “Data and digital ecosystems are critical for responsible innovation in the agriculture sector. The agriculture data exchange and the agriculture data management framework highlight the power of multi-stakeholder communities and collective action in addressing complex challenges in the agriculture sector.”

The software platform facilitates secure, standards-based exchange of data between agricultural data users (e.g. agri application developers) and agricultural data providers (e.g. Government Agencies, Private Companies, NGOs, Universities, etc.). Commenting on the launch, Prof G Rangarajan, Director, IISc, said, “ADeX will prove to be a game changer in the agriculture ecosystem providing impetus to research and innovation in the sector and creating value by mobilising data for healthy, sustainable, and environmentally friendly agricultural practices.”

In Phase-I of the project, the ADeX Platform is currently deployed in the district of Khammam and over a period, will be expanded to the entire State. At the launch, several Agtechs demonstrated their digital solutions using data accessed through ADeX, such as:

• Market Advisory: Utilising daily Telangana agriculture market prices, farmers will have access to market prices of all commodities across different markets in the state daily. With increased transparency, it will enable farmers to take informed decisions regarding crop selection, timing of harvest, and choosing markets that offer better prices, ultimately maximising their profitability.
• Pest Prediction Advisory: Leverages pest data across 33 districts in Telangana, dynamic weather, and prevailing pest conditions to provide targeted pest alerts to the farmers, allowing them to take timely action, reducing crop losses and costs. It also supports sustainable farming by promoting pest management strategies.
• Ease of Access to Credit: Enables faster disbursement of credit or other financial support to farmers by supporting banks and financial institutions to harness data-driven insights to create a farmer credit assessment report. With the growth in ecosystem and education and awareness efforts, more and more agtechs are invited from both public and private sector to utilise the platform to build, innovate and deploy solutions for betterment of the farmers.

Agriculture Data Management Framework

11 August 2023 also marks the release of the Agriculture Data Management Framework (ADMF) by the Government of Telangana. The framework has been developed after extensive public and industry consultations on the crucial aspects of data protection, management, and innovation. Informed by domestic laws and regulations and converging global best practices, ADMF is an agile, forward-looking framework, with the objective of facilitating consent-based responsible data sharing.

ADMF is applicable to all government departments dealing with agricultural activities as well as all agriculture information users and providers. Guided by best practices and well-established principles of notice, consent-based collection and processing of data and purpose-based limitation in utilising the data, the framework provides for robust grievance redressal mechanism.

Hon’ble Minister for Agriculture, Shri Singireddy Niranjan Reddy expressed during the event, “ADMF and ADeX are set to drive agricultural progress by facilitating the digitisation of agriculture-related data while upholding farmers’ data privacy. This will help Government and private sector to provide better solutions to farmers ultimately increasing agricultural productivity in Telangana.”

The framework envisages an inter-departmental committee, which will issue standard operating procedures and guidance on key aspects such as access controls, data quality, data service providers etc.

The core principles of ADMF are built into the ADeX platform which ensures safety and protection for personal data collection and use. These twin initiatives will create a comprehensive data economy for the future of agriculture and will enable large scale innovation that will drive impact to the farmer community.

Photo caption: Left to Right – Smt Rama Devi Lanka, Director, Emerging Technologies, ITE&C Department, Govt of Telangana; Shri J Satyanarayana, Chief Advisor, WEF; Shri Jayesh Ranjan, Principal Secretary, IT E&C and Industries and Commerce, Govt of Telangana; Shri KT Rama Rao, Hon’ble IT Minister, Govt of Telangana, Shri M Raghunandan Rao, Secretary, Ministry of Agriculture, Govt of Telangana, Dr Inder Gopal, Research Professor, Indian Institute of Science

Contact:

IUDX Programme: info@iudx.org.in

IISc Office of Communications: news@iisc.ac.in

10 August 2023

Graduate Aptitude Test in Engineering (GATE) is a prestigious national-level examination that assesses candidates for comprehensive understanding in various undergraduate-level subjects of engineering, technology, science, architecture, and humanities.

IISc, Bengaluru will be the organising institute for GATE 2024. The examination is conducted by IISc and seven IITs comprising IIT Bombay, IIT Delhi, IIT Guwahati, IIT Kanpur, IIT Kharagpur, IIT Madras, and IIT Roorkee, on behalf of the National Coordination Board (NCB) – GATE, Department of Higher Education, Ministry of Education (MoE), Government of India.

Candidates who qualify GATE can seek admission to master’s programmes and direct doctoral programmes in engineering, technology, architecture, science, and humanities; and doctoral programmes in relevant branches of engineering, science, and humanities, with possible financial assistance in institutions supported by Ministry of Education (MoE) and other Government agencies. GATE score is also used by some colleges and institutions for admission to postgraduate programmes without MoE scholarship. Several Public Sector Undertakings (PSUs) have also been using GATE score for recruitment. Several other reputed organisations are also likely to use GATE score in their recruitment process.

GATE 2024 will be conducted as a computer-based test (CBT), with 30 test papers that will be in the English language. Candidates have the option to appear for one or two test papers from the allowed two-paper combinations. The GATE score obtained by the candidates will remain valid for a period of three years from the date of announcement of results.
GATE 2024 also features a new test paper on ‘Data Science and Artificial Intelligence’, which caters to the needs of aspirants who wish to pursue higher education in these cutting-edge areas.

The application portal is expected to open in the last week of August 2023. The examination will be conducted on the 3rd, 4th, 10th, and 11th of February 2024. The examination will be conducted in both forenoon and afternoon sessions on each of these days.

For more details, visit GATE 2024 website: https://gate2024.iisc.ac.in/

2^nd August 2022

Photo Credits: KG Haridasan & S Tharesh

On 29 July 2022, HDFC Bank Parivartan signed a Memorandum of Understanding (MoU) with the Indian Institute of Science (IISc). Under the MoU, HDFC Bank Parivartan has pledged Rs 107.76 crore to support three wings of the Bagchi-Parthasarathy Hospital at IISc. The three wings to be supported by the Bank are the Cardiology wing, Radiology wing, and Emergency Medicine wing.

IISc is setting up a multi-speciality, not-for-profit, 832-bed hospital, called the Bagchi-Parthasarathy Hospital, along with a Postgraduate Medical School within its Bengaluru campus. The hospital is expected to be fully functional by the end of 2024 while the first batch of MD/PhD students will be admitted in the year 2025.

HDFC Bank has partnered with IISc for the first time with the aim of improving the healthcare infrastructure in the region.

Listed below is the direct impact of HDFC Bank’s partnership with IISc within the first five years (2025-2029):

“HDFC Bank’s partnership with IISc Bangalore is aligned with our commitment to improve healthcare and medical infrastructure across the country,” said Ms Ashima Bhat, Group Head, ESG & CSR, Business Finance & Strategy, Administration and Infrastructure, HDFC Bank. “The new hospital and the medical school will not only bolster the healthcare needs of the entire region but will also provide a new generation of physician-scientists. HDFC Bank has always supported nation-building activities and the impact of the medical school/hospital is expected to set the tone for sustainable health goals and policies for the nation. It will serve as a model of clinical research and training that can be emulated across the country. We look forward to working closely with IISc Bangalore in this journey.”

Photo Credits: KG Haridasan & S Tharesh

Prof Govindan Rangarajan, Director, IISc said, “After pursuing excellence in science and engineering research for 113 years, IISc has embarked upon a new frontier of clinical research through the establishment of the Bagchi-Parthasarathy Hospital and IISc Medical School. We are thankful to HDFC Bank for being a major partner in this new initiative and providing support for the establishment of three important wings: Cardiology, Radiology, and Emergency Medicine at the Hospital. We look forward to expanding this engagement with HDFC Bank in transforming the future of healthcare in this country.”

HDFC Bank is the amongst the largest corporate CSR spenders in the country. The bank’s key focus areas include care for climate, rural development, education, skill development, healthcare & hygiene and financial literacy under Parivartan.

About HDFC BANK: 

For more information, please visit: www.hdfcbank.com

Media queries: 

Sherna D’Mello
Corporate Communications
HDFC Bank Ltd., Mumbai
Mobile: 09920888014
sherna.dmello@hdfcbank.com

Madhu Chhibber
Head, Corporate Communications
HDFC Bank Ltd., Mumbai
Mobile: 9833775515
madhu.chhibber@hdfcbank.com 

IISc Office of Communications
news@iisc.ac.in

10^th August 2022

– Pratibha Gopalakrishna

Researchers at the Indian Institute of Science (IISc) have identified a way to estimate ancient seawater temperature by probing tiny bones in the ears of fish.

Oceans cover three quarters of the Earth’s surface and host many remarkable life forms. Earth scientists have been attempting to reconstruct the seawater temperature over time, but it is not easy to do so. “When you go back in time, you don’t have any fossilised seawater,” explains Ramananda Chakrabarti, Associate Professor at the Centre for Earth Sciences (CEaS), IISc, and corresponding author of the study published in Chemical Geology. Therefore, he and his PhD student, Surajit Mondal, in collaboration with Prosenjit Ghosh, Professor at CEaS, turned to otoliths – tiny bones found in the inner ear of fish.

Like corals, otoliths are made of calcium carbonate and grow throughout a fish’s lifetime by accumulating minerals from seawater. Similar to tree rings, these otoliths also hold clues to the fish’s age, migration patterns, and the type of water that the fish lived in. For several years, Chakrabarti and his team have been tracking calcium carbonate deposits found in tiny animals like corals or foraminifera. In the current study, they chose otoliths as scientists have discovered fossilised otolith samples dating as far back as the Jurassic period (172 million years ago).

The researchers used six present-day otolith samples collected from different geographical locations along the east coast of North America. They analysed the ratio of different calcium isotopes in these otoliths with a Thermal Ionisation Mass Spectrometer (TIMS). By measuring the ratios of calcium isotopes in the sample, they were able to correlate it with the seawater temperatures from which the fish were collected. “We demonstrated that calcium isotopes are a powerful tracer of water temperature, and Surajit’s efforts make our lab the only lab in the country that can actually measure these isotopic variations,” says Chakrabarti. In addition to calcium isotopes, the team also analysed the concentration of other elements like strontium, magnesium, and barium, and their ratios in the same sample, and collated the data together to tease out a more accurate value for seawater temperature within a range of plus or minus one degree Celsius when compared to the actual value.

Organisms that live in the ocean are extremely sensitive to temperatures. A two-degree temperature rise could lead to the extinction of several species. In addition, because the atmosphere and the ocean are “on talking terms”, says Chakrabarti, a lot of the carbon dioxide in the atmosphere eventually dissolves into the ocean, and this ability to dissolve carbon dioxide is also linked to seawater temperature – the lower the temperature, the more carbon dioxide is trapped. Just like a carbonated drink that loses its fizz as it warms up, the ocean loses its ability to hold carbon dioxide as it gets warmer.

Because of the close correlation they found between calcium isotope ratios and temperatures, the authors are confident that their approach can now be used on fossilised samples. Mapping early seawater temperatures is important to better understand Earth’s history, they say. “What happened back in time,” says Chakrabarti, “is key to our understanding of what will happen in the future.”

REFERENCE:

Mondal S, Chakrabarti R, Ghosh P, A multi-proxy (δ44/40Ca, Sr/Ca, and Δ47) study of fish otoliths for determination of seawater temperature, Chemical Geology (2022).

https://doi.org/10.1016/j.chemgeo.2022.120950

CONTACT:

Ramananda Chakrabarti
Associate Professor
Centre for Earth Sciences (CEaS), Indian Institute of Science (IISc)
Email: ramananda@iisc.ac.in
Phone: +91-80-2293-3003

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.inor pro@iisc.ac.in.

11^th August 2022

The Indian Institute of Science (IISc) today entered into an MoU with Mr Prashanth Prakash, founding partner of Accel and Chairman of Karnataka’s Startup Vision Group, to set up a geriatrics wing as part of IISc’s upcoming Bagchi-Parthasarathy hospital.

The Shantha & Prakash Geriatrics Wing is expected to be operational by the start of 2025. The wing will be equipped with state-of-the-art facilities in geriatrics to support academic and research programmes, and to enable PG students to undergo world-class training. It will take forward the IISc Medical School’s objective of integrating science, engineering and medicine under a single umbrella to produce a new generation of physician-scientists.

Commenting on the occasion, Prof Govindan Rangarajan, Director, IISc, said, “We thank Mrs & Mr Prashanth for their generosity in establishing this important geriatrics wing. Despite advances in integrative medicine, long-term care including post-acute care of the elderly is a universal challenge. With increasing life expectancy, it is also crucial to ensure healthy aging of the population. These multiple challenges require an interdisciplinary approach for effective care and we are sure that the Shantha & Prakash Geriatrics Wing will fuel and drive the much-needed innovation in this space.”

Mr Prashanth said, “Proactively managing age-related comorbidities will help prolong the period during which individuals can enjoy maximum physical and cognitive independence. Through physician-scientists, there is immense potential for the Institute to bring advancements in Gerosciences and Healthy-aging to help people live their most extended, healthiest lives possible.”

Contact:

IISc Office of Communications | news@iisc.ac.in

19^th August 2022

The Centre will focus on advancing research on heart, bone, cartilage and cancer through the use of 3D bioprinting 

CELLINK, the global leader in developing 3D bioprinters, and the Indian Institute of Science (IISc) are partnering to establish a Centre of Excellence (CoE) for 3D bioprinting in Bengaluru, India. The CoE, the first of its kind in the subcontinent, will be housed in the Centre for BioSystems Science and Engineering (BSSE) at IISc, and will provide access to 3D bioprinting systems, enabling researchers to accelerate their work across critical applications, with the ultimate goal of improving health outcomes. An MoU was signed to formalise the collaboration on 18 August 2022.

3D bioprinting is the application of additive manufacturing techniques to live cells, growth factors and/or biomaterials to fabricate biomedical parts, often with the aim to mimic natural tissue characteristics. 3D bioprinting covers a broad range of bioprinting techniques and biomaterials. Currently, bioprinting can be used to print tissue and organ models to help research drugs and potential treatments.

Photo: KG Haridasan

The new CoE will house several state-of-the-art 3D bioprinters from CELLINK and will serve as a hub for several research initiatives and training activities related to this emerging and exciting technology. Prof Govindan Rangarajan, Director, IISc, stated, “The CoE will contribute towards exploring new pathways in 3D bioprinting research and technology development. This would also align very well with the new initiative that we have launched to establish a post graduate medical school at IISc. I hope that the interdisciplinary collaboration through the CoE will create new medical technologies for affordable healthcare.”

Photo: KG Haridasan

IISc and CELLINK will work together to conduct workshops aimed at providing researchers within the institute, and elsewhere, the skills necessary to utilise 3D bioprinting in their work and reap the benefits of 3D cell culture. In addition to this, the two will undertake and advise on research projects across multiple applications spanning the fields of tissue engineering, drug discovery, material science and regenerative/personalised medicine. The Centre will have a keen focus on work around the heart, bone, cartilage and cancer.

“We are excited to host this CoE in the Institute, which will help to initiate cutting-edge research in an emerging field of technology with immense potential to benefit human health,” said Prof Narendra Dixit, Chairperson of BSSE.

“It’s an honour to collaborate with one of the most prominent science institutes in India. India has long been at the forefront of scientific discovery, and with the exceptional talent and deep-rooted passion to translate research from the benchtop to the clinic, we are confident that this Centre of Excellence will make a lasting impact on the progress within research in the fields of heart, bone, cartilage and cancer. With IISc we have a tremendous partner and we look forward to creating the future of health together,” added Ms Cecilia Edebo, CEO of CELLINK.

About BSSE:

The Centre for BioSystems Science and Engineering (BSSE) at the Indian Institute of Science (IISc) was founded in 2015, with a vision to develop and apply interdisciplinary approaches for understanding and manipulating biological systems. Since its inception, the Centre has been running a successful PhD programme in the broad area of Bioengineering. The programme was expanded to clinician-scientists, in collaboration with leading medical centres in the country. A new MTech programme in Bioengineering has been initiated in 2022.  Research at the Centre spans a spectrum of areas at the interface of biology and the physicochemical sciences, with a focus on problems of importance to clinicians and industry.

About CELLINK:

CELLINK is creating the future of health as part of BICO, the world’s leading bioconvergence company. When CELLINK released the first universal bioink in 2016, it democratized the cost of entry for researchers around the world and played a major role in turning the then up-and-coming field of 3D bioprinting into a thriving $1 billion industry. Today, the company’s best-in-class bioinks, bioprinters, software and services have been cited in over 700 publications and are trusted by more than 1,000 academic, pharmaceutical and industrial labs.

With a comprehensive portfolio of world-class 3D bioprinters and bioinks CELLINK’s technology enables the printing of human tissues and organs, which enable faster and more accurate models for drug development, while replacing animal experiments and paving the way to save lives by reducing organ rejection and potentially solve the problem with lack of donors.

CONTACT: 

IISc 

IISc Office of Communications | news@iisc.ac.in

CELLINK: 

Avi Minocha, Head of Marketing | akm@cellink.com

30^th August 2022

– Pratibha Gopalakrishna

During the first COVID-19 wave, when Saumitra Das and colleagues were sequencing thousands of samples every day to check for SARS-CoV-2 variants as part of INSACOG, the Government of India’s genome surveillance initiative, they were racing against time to track mutations as they appeared. “If we wanted to predict whether one of these mutations was going to be dangerous from a public health perspective, we needed an assay system,” says Das, Professor at the Department of Microbiology and Cell Biology (MCB), Indian Institute of Science (IISc).

The assay protocol widely followed, involved isolating the virus from the samples, creating multiple copies of the virus, and studying its transmissibility and efficiency at entering living cells. Working with such a highly infectious virus is dangerous and requires a Bio Safety Level-3 (BSL-3) lab, but there are only a handful of these labs across the country equipped to handle such viruses.

To address this problem, Das and his team, along with collaborators, and with funding from the Department of Biotechnology (DBT), have now developed and tested a novel virus-like particle (VLP) – a non-infectious nanoscale molecule that resembles and behaves like the virus but does not contain its native genetic material – in a study published in Microbiology Spectrum.

TEM image of gold particle labelled purified VLP. Image Credit: Raheja et al. 

Such VLPs have several uses. They can not only be used to safely study the effect of mutations that may arise in SARS-CoV-2 – without requiring a BSL-3 facility – but can also potentially be developed into a vaccine candidate that can trigger an immune response in our bodies. Soma Das, a DST Woman Scientist in the Department of Biochemistry and one of the authors, adds that these VLPs can also be used to cut down the time taken to screen drugs that can fight the virus.

Das’ lab has previously studied the Hepatitis C virus for 28 years. They have shown that VLPs can be used as vaccine candidates to trigger an immune response. When the pandemic hit, Das and his team began working on a VLP for SARS-CoV-2. They first had to artificially synthesise a VLP with all the four structural proteins – spike, envelope, membrane and nucleocapsid – seen in the actual virus. “The main challenge was to express all four structural proteins together,” says Harsha Raheja, PhD student at MCB and first author of the study.

VLPs (visible as green dots) in cells (outlined by red colour) Image Credit: Raheja et al. 

SARS-CoV-2 replicates by producing each structural protein separately and then assembling them into a shell containing the genetic material inside to form an active virus particle. To recreate this, the team chose a baculovirus – a virus that affects insects but not humans – as the vector (carrier) to synthesise the VLPs, since it has the ability to produce and assemble all these proteins and replicate quickly. Next, the researchers analysed the VLPs under a transmission electron microscope and found that they were just as stable as the native SARS-CoV-2. At 4 degrees Celsius, the VLP could attach itself to the host cell surface and at 37 degrees Celsius (normal human body temperature), it was able to enter the cell.

When the team injected a high dose of VLPs into mice in the lab, it did not affect the liver, lung, or kidney tissues. To test its immune response, they gave one primary shot and two booster shots to mice models with a gap of 15 days, after which they found a large number of antibodies generated in the blood serum of the mice. These antibodies were also capable of neutralising the live virus, the team found. “This means that they are protecting the animals,” explains Raheja.

The researchers have applied for a patent for their VLP and hope to develop it into a vaccine candidate. They also plan to study the effect of the VLP on other animal models (using the expertise of SG Ramachandra, one of the inventors), and eventually humans. Raheja says they have also developed VLPs that might be able to offer protection against the more recent variants like Omicron and other sub lineages.

REFERENCE: 

Raheja H, Das S, Banerjee A, Dikshaya P, Deepika C, Mukhopadhyay D, Ramachandra SG, Das S, RG203KR mutations in SARS-CoV-2 Nucleocapsid: Assessing the impact using Virus-like particle model system, Microbiology Spectrum, 2022.

https://doi.org/10.1128/spectrum.00781-22

CONTACT: 

Saumitra Das
Professor, Department of Microbiology & Cell Biology (MCB),
Indian Institute of Science (IISc)
Email: sdas@iisc.ac.in
Phone: 080-2293 2886

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.inor pro@iisc.ac.in.