In a virtual ceremony on 2 December, 2021, the Infosys Science Foundation (ISF) announced the winners of the Infosys Prize 2021. The laureates were chosen by a select jury of eminent leaders from a pool of 201 candidates, representing six categories: Engineering and Computer Science, Humanities, Life Sciences, Mathematical Sciences, Physical Sciences, and Social Sciences. The awardees were presented with a gold medal, a citation for contributions to their field of study, and a cash award of USD 100,000.

Every year, the Infosys Prize celebrates outstanding achievements in contemporary science and research and sets up the awardees as role models to promote an environment of scientific enquiry among Indian youth.

“Given the size of India and India’s population, even if you have a small percentage of people who become passionate about science, that can really change the number of scientists that we can have in the country,” said Gagandeep Kang (Chief Guest, and Infosys Prize laureate in 2016). Kang spoke about how in the past few centuries, and likely in the future, the history of the world has and will be shaped by countries that lead in science and intellectual exploration. “For any nation and society, world-leading science is a matter of prestige and a contribution to excellence in the country and the world. Recognition of exploration, innovation, and response to scientific and societal challenges is the goal of the Infosys Prize. Awards such as these create role models of science and scholarship that future generations can emulate,” she added.

The laureates

Chandrasekhar Nair

Chief Technical Officer, Molbio Diagnostics, Bengaluru

The Infosys Prize 2021 in Engineering and Computer Science was awarded to Chandrasekhar Nair for the development and large-scale deployment of TrueNat, a revolutionary point-of-care testing platform for polymerase chain reaction (PCR)-based diagnostics. The Chair for this category, Aravind, spoke about how TrueNat has enabled rapid testing for COVID-19 and tuberculosis in India and other resource-limited countries.

TrueNat is a battery-operated, rugged, field-usable PCR device that requires minimal training of operators. It can test for more than 30 diseases within an hour even in resource-limited settings. This rapid testing system enables point-of-care testing for early detection of diseases, which is crucial for faster recovery and breaking the chain of community spread.

Ângela Barreto Xavier

Senior Researcher, Institute of Social Sciences, University of Lisbon, Portugal

Ângela Barreto Xavier was awarded the Infosys Prize 2021 in Humanities for her in-depth research into the history of conversion and violence in the Portuguese empire in India, especially Goa. The Chair for Humanities, Akeel Bilgrami, said that Xavier’s sophisticated analysis and extensive writing on the subject (in English and Portuguese) have made her an important voice on colonial and imperial history.

Xavier’s work includes investigations into the history of political ideas, and the cultural history of early-modern empire, especially those involving religion, science, power, and cultural geopolitics.

Mahesh Sankaran

Professor, National Centre for Biological Sciences, Bengaluru

The Infosys Prize 2021 in Life Sciences was awarded to Mahesh Sankaran for his pioneering research on the ecology of tropical savanna ecosystems and the biodiversity of Indian ecosystems such as the Western Ghats. The Chair for this category, Mriganka Sur, spoke about how Sankaran’s involvement in international reports on climate change and biodiversity have impacted rational conservation strategies.

Sankaran has worked extensively in Africa and India on long-term changes in grasslands and tropical rainforests. His current interests are focused on savanna structure and function; long-term dynamics, land-use changes, and ecosystem services in tropical rainforests; climate change and ecosystem dynamics in high-altitude grasslands and dry savannas; and transitions from grasslands to forests.

Neeraj Kayal

Principal Researcher, Microsoft Research Lab, Bengaluru

Neeraj Kayal won the Infosys Prize 2021 in Mathematical Sciences for his contributions to computational complexity. The Chair for this category, Chandrashekhar Khare, explained that Kayal’s theoretical work on complexity theory provides the mathematical tools to understand the efficiency and limitations of algorithms that are vital to modern life.

Kayal’s innovative and extensive work on algebraic computation includes the development of lower bound techniques, proving the limitations of this natural model. He has also designed efficient algorithms for reconstruction and equivalence of such algebraic circuits.

Bedangadas Mohanty

National Institute of Science Education and Research, Bhubaneswar

Bedangadas Mohanty won the Infosys Prize 2021 in Physical Sciences for his investigations of the nuclear force. The Chair for Physical Sciences, Shrinivas Kulkarni, spoke about how Mohanty’s work contributes invaluable knowledge that forms the basis of exciting work done by astronomers, nuclear
chemists, physicists, and anyone who studies or uses nuclear energy.

At the Brookhaven National Laboratory and the European Organization for Nuclear Research (CERN), Mohanty determined the transition temperature of the quark-gluon plasma to hadronic matter, observed heavy antimatter nuclei, nuclear spin-orbital angular momentum interactions, and other effects in quark-gluon plasma.

Pratiksha Baxi

Associate Professor, Centre for the Study of Law and Governance, Jawaharlal Nehru University, New Delhi

Pratiksha Baxi was awarded the Infosys Prize 2021 in Social Sciences for her pioneering work on sexual violence and jurisprudence. The Chair for this category, Kaushik Basu, spoke about how Baxi’s work brilliantly combines legal studies, sociology, and anthropology and has profoundly influenced a growing field of inquiry into the social life of law.

Baxi’s extraordinary ethnographic research and meticulous analysis reveal how gender-based violence is reproduced by judicial practice.

Speaking about the history of the Infosys Prize, Kris Gopalakrishnan, President of ISF, said that over the last 13 years, the Foundation has recognised excellence in research and scholarship. He highlighted that in research, results may not always be immediately apparent; however, the long arc of knowledge, discovery, and invention can benefit mankind in unexpected ways as with the case of mRNA vaccines during the COVID-19 crisis. “By recognizing and celebrating the creativity and innovation of these remarkable individuals, we hope to inspire and encourage others and society at large. With the Infosys Prize, we not only reward apparent breakthroughs but also the far-reaching potential of the work of these stellar researchers and scholars,” he added.

The International Genetically Engineered Machine (iGEM) is a non-profit organization that aims to promote research in synthetic biology. It provides a platform for students and collaborators all around the world to combine biology and engineering to develop new biological systems and use them productively in society.

Every year, iGEM conducts an iGEM Competition, which invites students working in the field of synthetic biology to showcase their projects. A locally-relevant problem or an issue of global significance is identified by graduate, undergraduate and high school students, and they devise a method to tackle it. The iGEM Competition started with 5 teams in 2004, and has grown to 353 teams across 40 countries in 2019. The participation from India has increased from 4 teams in 2011 to 11 teams in 2021.

This year, two new grant opportunities have been introduced for students: the Team Impact Grant and Safety and Security Grant. The former grant is provided in partnership with the Frederick Gardner Cottrell Foundation and supports projects on topics like climate change, global pandemic response, agriculture, biomaterials and drug discovery. The latter grant is based on the belief that engineering biology is only beneficial if it is safe. Hence, it focusses on and encourages people working in the field of bio-safety and bio-security. The award of grants is primarily based on the aim of the project, impact in the community and the need for a grant to accelerate the project.

The iGEM 2021 grant was announced in May 2021. The teams were instructed to register for the competition by May and apply by June. The size of each team was restricted to around 8–15 members, from various disciplines besides biology (like computer science, art and design, marketing and mathematics) along with two academic instructors (preferably from the same institution). The students were encouraged to seek advice from multiple experts in their subject area to improve their projects.

After registration, the teams were required to complete a set of 12 deliverables including safety form, promotion video, team wiki page, poster, presentation, judging form (to be sent to the judges for evaluation), project attribution and description, and title and abstract within their respective deadlines. A ‘team roster’ was to be maintained as an official record of the iGEM team and others involved (professors, teachers, instructors and advisors). It was necessary for each team to choose a track that they would compete in the Giant Jamboree. Based on these tracks, the teams were grouped together for the final presentation.

A sum of $2500 was awarded to each winning team. Along with conducting high throughput experiments, this money could be invested in various outreach and educational campaigns to communicate with the stakeholders. Around 220 teams applied this year and only 90 teams were selected. The winners of the competition have shared their findings in the online iGEM 2021 Giant Jamboree held between 4–14 November.

One of the winning teams was from the Indian Institute of Science, Education & Research, Thiruvananthapuram (IISER - TVM). The team members explain, “The grant will ensure that our experiments are not limited by the number of replicates and that our vision for educating the community about synthetic biology is fulfilled.” The IISERTVM team is a 16-member team composed of graduate students, headed by Abhishek Raghunathan and Tejas Sabu. They studied chitinases (fungal cell wall-degrading enzymes) as potential antifungal drugs. They elucidate the origin of their project idea: “Our project started with the aim of decontaminating walls off fungal growth and discoloration by purifying chitinase enzymes to kill them. However, as the pandemic grew worse, cases of invasive fungal infections skyrocketed. This prompted us to view our enzymes in a new light as potential therapeutic drugs.” The team has engineered these enzymes to be more substrate specific and developed a robust delivery system for in vivo therapeutic purposes.

Mayuri Rege, faculty co-ordinator of the gold-medal winning team (in iGEM 2018) from Ramnarain Ruia College of Science and Arts, Mumbai says, “The most impactful part was that this early international exposure helped my students appreciate that true competition is often beyond their classroom. At the same time, when they saw overseas students also faced challenges like they did, it levelled the playing field and gave them the confidence to tackle such situations."

As a whole, the iGEM Competitions beautifully balance the twin virtues of a bird's eye view and detailed analysis of any subject. This helps greatly in catalysing the growth of the participants as individuals and as a team.

Mycobacterial infections have been a lingering concern due to their high incidence and growing antibiotic resistance. A team of researchers led by Rachit Agarwal, Assistant Professor at the Centre for BioSystems Science and Engineering, Indian Institute of Science (IISc), Bengaluru tried a different approach to control mycobacterial infections, by exploring the potential of phages for infection management.

Among the various mycobacterial infections, tuberculosis (TB) is one of the leading causes of death worldwide and poses a global health hazard. According to the World Health Organization (WHO) annual TB report published in 2021, nearly 9.9 million people are ill due to TB and 1.3 million deaths have been estimated. This necessitates novel treatment or vaccines in addition to improved diagnostics and better health coverage.

Tuberculosis—a communicable disease, often transmitted through the air—is characterized by infection of specialized immune cells in the lungs. Although these immune cells fire an immune response, the bacteria outsmart them by surviving in adverse conditions. Tuberculosis has been of special concern due to its high occurrence in developing countries, the requirement for long-term treatment and the development of multi-drug resistance. Hence, irrespective of current treatment strategies, much research has been dedicated to device better therapy measures to control and fight the disease.

An earlier study has shown the potential of using phages, which are specific to bacteria but harmless to humans, to treat bacterial infections in a cystic fibrosis patient. Inspired by this study, Rachit Agarwal’s team utilized viruses that infect, multiply, and kill bacterial cells—known as bacteriophages or simply phages—to design an anti-mycobacterial therapy. To test the possibility of using phage therapy for controlling mycobacterial infections, “we first started experiments with Mycobacterium smegmatis (a faster growing species of mycobacteria) and were excited with the initial success. That led us to perform a detailed study to understand if phages are effective in various pathophysiological conditions,” says Agarwal. The initial observation of reduced mycobacterial growth within 2–5 hours of introducing phages seemed encouraging. Therefore, similar studies were carried out using phage cocktails, which also resulted in the decrease of bacterial growth. Agarwal’s team decided to further explore the possibilities of using these phage cocktails to effectively treat mycobacterial infections.

M. smegmatis is a fast-growing mycobacterial species when compared to other mycobacterial species. During infection, mycobacteria usually thrive in adverse conditions often characterized by low levels of pH, nutrition and oxygen. Therefore, further experiments were conducted under such adverse conditions using M. smegmatis to observe quantifiable results. Subsequently, detailed studies under disease-mimicking adverse conditions showed that phages were effective in decreasing mycobacterial growth.

M. tuberculosis (Mtb), the causative agent of tuberculosis, is an example of a slow-growing mycobacterium. Owing to the impact of tuberculosis on global health, phage therapy was used in combination with the antibiotics that are currently used to treat tuberculosis. M. smegmatis cultures were co-treated with phages and antibiotics, and a significant reduction in mycobacterial growth was observed. Given these optimistic results in M. smegmatis, phage treatment was tried on an avirulent strain (a non-disease causing variety) of M. tuberculosis, and successful prevention of mycobacterial growth was observed up to 57 days.

This study, on understanding the infection dynamics of phages in slow- and fast-growing mycobacteria, is important due to its clinical significance in treating tuberculosis. Amit Singh, Associate Professor at the Department of Microbiology and Cell Biology, IISc, explains the importance of the study: “The study showed that phages are synergetic with the clinically-relevant anti-TB drugs. Therefore, phages can be used against drug-resistant mycobacteria. However, the true potential of these approaches requires future efficacy studies using mycobacteriophages cocktails for targeting pathogenic Mtb inside the infected human host cells.”

Scientists from the University of Allahabad, Prayagraj, are closer to understanding how human stem cells work. They have identified the core genes that allow stem cells to exist in distinct functional states. Knowledge of the exact molecular mechanism behind these states paves the way for newer methods of culturing stem cells and using them for therapeutic or biomedical applications.

Stem cells are special cells that develop into different cell types in the human body, for example, nerve cells or muscle cells, making them highly desirable candidates for treating diseases. Stem cells are of two kinds : adult and embryonic stem cells (Fig. 1). Adult stem cells primarily develop into a particular cell type — for example, muscle tissue stem cells will only give rise to muscle cells. On the other hand, embryonic stem cells (ESCs), found in three to five-day-old embryos, are pluripotent; that is, they can grow into almost any type of cell in the adult body. However, owing to ethical issues, human embryonic stem cells are not used for laboratory experiments and therapeutic applications.

Interestingly, research has shown that cells of the body (e.g., skin cells, blood cells, etc.) can be altered in the laboratory to behave more like embryonic stem cells. These are called induced pluripotent stem cells (iPSCs) (Fig. 2).

Pluripotent cells exist in two distinct functional states —naive and primed. Naive cells are unrestricted and grow into any cell type, whereas primed cells are inherently biased towards their cell type and are not as amenable as their naive counterparts. Anup Som, principal investigator, University of Allahabad and corresponding author of this study, says, “iPSCs are an effective alternative to embryonic stem cells. However, they are most useful when equivalent to naive cells. Hence, it is important to understand the mechanism behind the two states of human pluripotency.”

Rakhi Pal, chief technology scientist, Institute for Stem Cell Science and Regenerative Medicine (InStem), Bengaluru, who was not part of the study, adds, “Greater clarity on the role of naïve and primed pluripotent cells in the origin of diseases can lead to targeted therapies and more specific drugs.”

Som’s team gathered gene expression data from previously published studies on naïve and primed human ESCs. They then used a bioinformatics method called weighted gene co-expression network analysis (WGCNA) to study the correlation between different sets of genes. The application also helps to identify a gene or a set of genes that cause a particular disease.

Using WGCNA, the team hoped to identify groups of genes that work in tandem to execute a specific function—in this case, maintaining the stem cells in either the naive or primed state. Two sets of genes stood out; the first set consisted of 4791 genes with the most significant activity in the naive state, while the second set comprised 5066 genes responsible for the primed state of pluripotency.

Their next step was to identify which of these genes code for transcription factors (proteins controlling the activity of a gene). The researchers compared their list of genes to a previously published catalogue of human transcription factors and found that 52 transcription factors were critical for the naive state and 33 factors for the primed state. Thus, these 85 transcription factors can now be considered key to controlling the switch from naïve to the primed state of pluripotency.

Pal highlights the challenges associated with such a study, “In biological research, new data emerge as we speak. Integrating findings from various research groups worldwide can be tough, and cell culture largely depends on the prevailing conditions in different laboratories. Normalising all that data to reach a stage where one can compare the results is an uphill task.”

Som and his team have their eyes set on their next goal. He says, “In the current study, we focus only on the protein-coding genes. In future studies, we aim to incorporate the role of non-coding DNA (DNA that does not directly provide instructions for protein synthesis, but indirectly may help in regulation) in the maintenance of pluripotency.”

The German Academic Exchange Service (DAAD) is the world's largest funding organization, supporting the international exchange of students and scholars to Germany. It offers outstanding international candidates access to excellent education, research opportunities, subject-oriented professional training, and intercultural experience. It is home to the theoretical quantum chemist Angela Merkel, Chancellor of Germany who became a zealous world leader. Her administration strengthened and internationalized German science. DAAD has funded over 80,000 students and scholars from India. This makes Indian students the second largest international group enrolled at German universities as of 2021.

DAAD goes beyond awarding grants and scholarships. It invests in the professional and personal development of its awardees. Most recently, when the pandemic left several Indians stranded in Germany, DAAD promptly facilitated the stay and visa extension of these scholars. “I am indebted to DAAD for providing me this opportunity to pursue my research project in Germany and bringing me safely back to India. It has been a life-changing experience for me”, expresses a KOSPIE Scholar.

DAAD offers a gamut of funding schemes that encourages Indians across all career stages to sojourn in Germany for internships, research projects, and networking. Here are a few programs:

1. Working Internships in Science and Engineering (WISE)

WISE focusses on Indian students from premier institutions pursuing a degree in natural sciences, engineering, or mathematics. It funds a research internship of 2 to 3 months at a public or state-funded higher education institution or a non-university research institute in Germany. The applicant must have a confirmed internship offer from a German professor. DAAD provides a monthly stipend, health insurance, and travel subsidy.

Jainam Jain, a WISE 2021 intern at TU Darmstadt in Mathematical Modeling and Analysis Department says, "Even though the program was held virtually, my internship experience was really good. The work environment is fantastic! I worked under the guidance of an eminent professor."

The deadline for applying this year is 8 November.

2. Bi-nationally Supervised Doctoral Degrees

This program enables Ph.D. scholars to undertake part of their research in Germany. DAAD finances monthly stipend, travel, health insurance, and research.

“My research institute and my German professor taught me how to see a problem and the myriad ways to solve it. I interacted with professors, research fellows, and imbibed their working styles. This is a good opportunity to experience the learning environment of Deutschland”, says a scholar who did his Ph.D. in collaboration with PLRI Institute of Medical Informatics, Technische Universität Braunschweig in 2017.

The deadline for applying this year is 20 October.

3. Research Stays for University Academics and Scientists

Networking in academia is an arduous process, especially internationally. This program opens a channel between Indian and German academicians by funding short research stays in Germany. University teachers, established academicians, and scientists working at a university or research institute in India are eligible.

The deadline for applying this year was 5 October.

4. Bilateral Exchange of Academics

This program promotes international relations through academic exchange. Scientists and faculty from the Indian Institutes of Technology (IITs) and The Council of Scientific & Industrial Research (CSIR) are eligible to switch with researchers in Germany for three months. The research project must be coordinated with the partner institution in Germany.

The deadline for applying this year was 5 October.

Inflammatory bowel disease (IBD) is a debilitating disease of the intestinal tract, plagued by chronic inflammation of the gut. A dysregulated gut immune response causes the persistent inflamed condition leading to erosion of the protective intestinal barrier.

Existing studies have shown that a series of molecular events called the NF-κB (NF-kappa B) canonical pathway plays a crucial role in triggering the immune response in the gut. Usually, the pathway controls the activity of a set of proteins called NF-κB transcription factors to regulate the inflammation process while fighting pathogens in the gut. However, in IBD, the regulation is skewed, leading to the hyperactivation of inflammatory proteins. The molecular details of what provokes this runaway process has remained elusive.

Now, a collaborative study by a team of researchers from the National Institute of Immunology, New Delhi, Indian Institute of Technology Delhi, New Delhi, All India Institute of Medical Sciences, New Delhi, and Agency for Science, Technology and Research (A*STAR), Singapore, has deciphered a mechanism underlying the aberrant inflammation in Inflammatory Bowel Disease. The study, led by Soumen Basak, Staff Scientist VI, National Institute of Immunology, revealed unwarranted crosstalk of the canonical pathway with another seemingly harmless pathway called the noncanonical NF-κB pathway.

NF-κB is a family of transcription factors – proteins that, once activated and inside the nucleus, can bind to specific DNA regions and help transcribe (or decipher) the target genes. This subsequently generates specific proteins for physiological responses. NF-κB factors respond to a variety of signals and activate the expression of immune response genes. Their nuclear activation is controlled by two signalling pathways: canonical and noncanonical, both regulating a myriad of physiological functions.

When pathogens invade, the canonical NF-κB pathway is activated and leads to the generation of an immune response. The canonical NF-κB pathway triggers the release of cytokines and mediates a controlled inflammatory process. Once the pathogens are flushed out, the triggers subside, and the canonical pathway is inhibited.

However, when the canonical pathway is hyperactivated, as seen in IBD, along with flushing out the pathogens, the over-abundant cytokines also destroy the mucosal barrier of the intestine. This exposes the intestinal epithelial tissue (the outermost layer of cells inside the intestine), causing uncontrolled inflammation and tissue damage at the affected site.

NF-κB factors also respond to signals via the noncanonical pathway, which regulates the development of immune organs and tissues. "The noncanonical pathway has different molecules that monitor other bodily functions, such as generating primary cells that form organs," says Basak.

Recent studies have shown that the two pathways are intertwined. However, whether the noncanonical NF-κB pathway has a role in IBD was not known. Noticing this, the team hypothesised that the noncanonical pathways could be playing an indirect role in regulating the inflammatory NF-κB activity and, in turn, modulating the inflammatory response in the gut.

The team conducted molecular analyses on colon biopsy samples of IBD patients and compared them with non-IBD control group samples. In the IBD patient samples, they found increased processing of a key protein of the noncanonical pathway, called p100.

p100 is encoded by a gene named Nfkb2. p100 is processed to generate another protein p52 during noncanonical signalling and p52 is responsible for inducing the target genes in the noncanonical NF-κB pathway. "We noticed up to 53% of IBD patients displayed elevated p100 processing to form p52," says Basak. So, the question now was whether the elevated noncanonical signalling enhanced the canonical pathway's activity in intestinal inflammation.

To find out, the researchers experimented on mice with chemically-induced intestinal inflammation as seen in IBD. First, they genetically engineered mice such that they lacked the Nfkb2 gene in the intestinal epithelial cells and treated them with a chemical reagent known to induce IBD-like conditions via the canonical pathway. Compared to mice with an intact Nfkb2 gene, the mice that lacked it showed significantly reduced canonical pathway activation subsequent to the chemical treatment, indicating its dependence on the Nfkb2 gene. "We performed gene expression analyses which revealed that noncanonical NF-κB signalling events were amplifying inflammatory gene expressions in the intestinal epithelial cells," says Meenakshi Chawla, first author of the study. This showed that the enhanced activity of the noncanonical pathway was causing unwarranted communication between the two pathways. This caused the heightened inflammation in gut epithelial cells leading to the chronically inflamed condition.

Ellora Sen, Scientist at the National Brain Research Centre, Manesar who was not involved in the research, says, "This study highlights the previously unknown crosstalk between the canonical and noncanonical NF-κB pathway that drives the hyper-inflammatory response in IBD. Thus, targeting Nfkb2 may hold promise as a therapeutic option, not only in IBD but several other inflammatory diseases."

Animal cells take in extracellular materials, a few proteins and lipids by a process called Endocytosis. Some of the endocytosed components are recycled back to the plasma membrane by a process known as recycling endocytosis. The material taken in is sorted within sorting endosomes; whatever is destined for recycling to the plasma membrane is then diverted into a tubular membranous network called the Tubular Recycling Endosomes (TRE).

Motor proteins play a key role in recycling endocytosis as they generate forces to lift the cargo and carry them to the cell periphery along pre-designated lanes of microtubules. The current study shows the mechanism of functioning of one such motor protein — KIF13A, belonging to the kinesin-3 family.

Subba Rao Gangi Setty, Associate Professor, Department of Microbiology and Cell Biology at IISc and one of the authors of the study says, “We discovered cargo transport mechanisms between endosomes and the plasma membrane in a cell, which is mediated by TREs. Our study illustrates how a family of enzymes called guanosine triphosphatases (GTPases) regulate the activity of KIF13A, which in turn controls what happens to the TREs. This was the key discovery in the study.”

KIF13A, acts in pairs to ferry TREs along microtubules. Wild-type (WT) KIF13A (or when not bound to cargo) exists as a single, inactive molecule. A previous study by the same group showed that the amino acid Proline at the neck of the KIF13A protein introduces a kink in the protein structure that hinders interaction with another KIF13A monomer. How then do two KIF13A monomers pair up to transport TREs along microtubules, has been an unanswered question for some time now.

The researchers, led by Virupakshi Soppina of IIT Gandhinagar, reveal that a protein called Rab22A, a GTPase, binds to the neck region of two inactive KIF13A monomers to activate them — ”like a zipper.” The researchers performed cloning and transfection experiments on cultured cells, followed by live cell imaging, direct fluorescence spectroscopy and in vitro single-molecule reconstitution assays to study the interaction between KIF13A and Rab22A. They found out that binding of Rab22A relieves the kink in the structure induced by Proline, and this opens up the KIF13A structure to pair up. If two inactive KIF13A monomers are akin to either sides of a zipper when it is open, the Rab22A can be compared to the slider that joins both sides and helps them pair up. Rab22A is the molecular switch that controls the two states of KIF13A — active and inactive.

Krishanu Ray, professor at Tata Institute of Fundamental Research, Mumbai, who was not involved in this study, sheds light on the importance of these findings, “ Sorting of proteins, lipids and other metabolites inside a cell is essential for life. This study improves our understanding of a basic cell biology concept underlying development, cancer, and neurobiology. With this knowledge, one can now work at rectifying problems in recycling and correct the disorder.”

The enormity of the findings is further heightened when one realises the challenges associated with such a study. Ray says, “The first challenge is to make motor proteins work when and where you need them to. Secondly, a cell repurposes one type of motor for multiple functions. Hence, it can be an uphill task to demonstrate a specific action played by Rab22A at a specific time point. I consider this study as an exquisite demonstration of a precise cell biology experiment.”

The authors believe that this study is the first of its kind to report a Rab protein regulating activity of a motor protein to facilitate intracellular transport. This knowledge is vital to further understand diseases arising from faulty Rab-motor protein interactions. Additionally, these findings are highly relevant in the current times —KIF13A has been known to play a role in the trafficking of viral particles. Understanding its regulation can be a step forward in the prevention or treatment of viral diseases.

TNQ’s Inspiring Science Award is given annually for the best paper in the life sciences published from India in the previous 12-month period. The award is open to scientists who are registered for a PhD or those within the first four years of their post-doctoral research.

The Inspiring Science Award 2022 is now open for entries and will close at midnight, on 15 October 2021.

2022 will be the sixth year of TNQ’s Inspiring Science Award, which has steadily gained recognition in the Indian life sciences community. The award aims to recognise and reward quality science, inspire scholarship, and encourage students of the life sciences to pursue excellence and to do significant and creative work. The jury consists of eminent scientists from around India who spend two months assessing the entries.

“The process of submission is simple and needs no recommendation, no nomination, or forward letter”, noted Anuranjan Anand, Associate Faculty and Chair, Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bengaluru in his address as the chief guest of the 2021 award ceremony held in January 2021.

The applications we receive are of impressive scope, spread and quality. For the last (2021) edition, the award received 554 entries from over 240 institutions across 100 cities in India. And the winner was…

Richa Mishra, for her paper ‘Targeting redox heterogeneity to counteract drug tolerance in replicating Mycobacterium tuberculosis’. Soumya Swaminathan, Chief Scientist, World Health Organization, Geneva, who was the special guest at the 2021 awards function said to Mishra about her work, “It is a very interesting exploration that you have done on the concept of drug tolerance in Mycobacterium tuberculosis… there have been many drugs that have been postulated to have an impact on drug tolerance. The evidence that you provide for chloroquine definitely needs further exploration. The animal models seem to be promising. We need to take this work further and see if it can go into the clinic.”

Mishra’s research was conducted at the Indian Institute of Science, Bengaluru, and her paper was published in AAAS’s Science Translational Medicine. She is currently a Post-doctoral Fellow at the Laboratory of Microbiology and Microtechnology, École polytechnique fédérale de Lausanne (EPFL), Lausanne.

The other finalists were:

• Santosh Kumar Kuncha (CSIR-Centre for Cellular and Molecular Biology, Hyderabad) for his paper ‘Genomic innovation of ATD alleviates mistranslation associated with multicellularity in Animalia’.

• Aarush Mohit Mittal (Indian Institute of Technology, Kanpur) for his paper ‘Multiple network properties overcome random connectivity to enable stereotypic sensory responses’.

• Soumik Ray (Indian Institute of Technology, Bombay) for his paper ‘α-Synuclein aggregation nucleates through liquid–liquid phase separation’.

• Ritika Tiwari (Indian Institute of Technology, Kanpur) for her paper ‘Androgen deprivation upregulates SPINK1 expression and potentiates cellular plasticity in prostate cancer’.

• Raj Kumar Verma (Centre for DNA Fingerprinting and Diagnostics, Hyderabad) for his paper ‘A bacteriophytochrome mediates interplay between light sensing and the second messenger Cyclic di-GMP to control social behavior and virulence’.

For the Inspiring Science Award 2022, eight papers will be shortlisted by the jury for the top pick. All finalists will receive an Apple laptop and a citation. The winner will receive the ISA medal, a citation, and a travel fellowship to a conference of their choosing anywhere in the world. During the pandemic, and while travel is restricted, the winner will receive a cash award of INR 2,00,000 in lieu of the travel fellowship.

Please visit https://isa.tnq.co.in/ for more information.

A team of researchers led by Karishma Kaushik, Assistant Professor from the Savitribai Phule Pune University (SPPU), Pune, has developed a new method to grow and study skin cells. This method uses at least five times lesser concentrations of foetal bovine serum (FBS), a central component of cell growth media. FBS is widely used in experiments to grow cells that mimic physiological conditions in the lab.

FBS is a cocktail of growth hormones, vitamins, proteins, fatty acids, and lipids. It facilitates the growth, survival, and proliferation of many human and animal cells in the laboratory. It is also preferred routinely in cell culture studies due to low levels of antibodies, which ensures minimum unwanted immune response when used in experiments. Usually, 10% vol/vol of FBS is added to the cell culture medium for experiments.

However, FBS is extracted from unborn foetuses of pregnant cows, raising numerous ethical concerns. Moreover, procuring FBS poses several economic challenges as it is a byproduct of slaughterhouses. “There is an increasing impetus to reduce and eventually replace the use of animals and animal products in advanced research,” says Kaushik. While this is a tall order per se, the development of cell culture methods that can reduce the use of animal serum is a viable place to start, she adds.

In the present study, the team developed two new methods with which two types of skin cells, fibroblasts and keratinocytes, could grow in a cell culture medium with only 1-2% FBS.

Keratinocytes are the cells that make up the dermis or the outermost layer of our skin. Fibroblasts reside in a layer just below the keratinocytes.

The major hurdle faced by the team was in growing the skin cells together (co-culture). “Fibroblast skin cells love serum-containing media. Keratinocytes, on the other hand, typically grow poorly in the presence of serum,” explains Kaushik. So, the researchers attempted to tweak the growth media components for the two cell types to overcome the hurdle.

They achieved a ‘sweet spot’ by (1) using cell-specific growth media, (2) by adding cell-specific additives in addition to the primary minimum cell growth media. They used commercially available and accessible cell growth media called Minimum Essential Medium (MEM), all-inclusive fibroblast and keratinocyte growth media (known commercially as FGM and KGM), and a ready-made cocktail of growth supplements for their experiments. MEM is a growth media containing minimum constituents required for the growth of animal or human cells in laboratories.

In the first protocol, the researchers added 1% FBS to fibroblast and keratinocyte specific growth media. In the second method, they combined 2% FBS with MEM; to this, they added supplements like proteins and vitamins to enhance cell growth. The combined approach resulted in a healthy proliferation of both keratinocytes and fibroblasts.

“Research is often constrained by resources and time. Hence, we tend to use tried and tested methods and don’t play as much with the methodology as we like. A study like this is filling the gap there,” says Joey Shepherd, Senior lecturer in Microbiology, University of Sheffield, United Kingdom. She was not involved in this study.

The team has also tested the applicability of their new growth media to study wound healing under laboratory conditions. They found that keratinocytes and fibroblasts show normal healing behaviour even with reduced FBS concentrations. The study opens avenues for further research and application in wound healing studies.

Three premier science academies — Indian Academy of Sciences (IASc), Bangalore, Indian National Science Academy (INSA), New Delhi, and National Academy of Sciences India (NASI), Prayagraj — jointly conducted a Science Leadership Workshop (SLW) from 22 to 28 June 2020. The virtual event was organised by Felix Bast, Associate Professor, Central University of Punjab, Bhatinda (CUPB). It was live-streamed on YouTube (the individual talks can still be accessed here).

The event brought together eminent speakers from across the world and from various areas of science. They shared their insights on what it takes to be leaders in science and some do's and don'ts of leadership in science. Over 20,000 registrants participated enthusiastically, making the event a successful learning experience. Additionally, a Facebook group functioned as an interaction platform and as a noticeboard during the program.

The article summarises some essential lessons gleaned from the workshop regarding leadership in science.

True learning cannot proceed unless you suspend your judgment – Ashutosh Sharma, Secretary, DST

On day one, Ashutosh Sharma, Secretary, Department of Science and Technology, Govt. Of India; Renu Swarup, Secretary, Department of Biotechnology, Govt. of India; Gagandeep Kang, Professor, Christian Medical College, Vellore; and Subhra Priyadarshini, Chief Editor, Nature India, spoke about the importance of teamwork.

Sharma said, "A leader should also be a follower" and "True learning cannot proceed unless you suspend your judgment". Some key takeaways from this session were:

• We are all driven by the same fears and aspirations; the difference lies in moving past the hurdles graciously.
• One should lead by example by getting past the hurdles and having long-term objectives.
• Reading science journalism should be the starting point for any aspiring writer.

On the second day, Ramakrishna Ramaswamy, Former President, Indian Academy of Sciences, Bangalore; Kiran Mazumdar-Shaw, Founder and Chairperson, Biocon India Ltd.; Felix Bast, (CUPB); and Anindita Bhadra, Associate Professor, Indian Institute of Science Education and Research (IISER), Kolkata, shed light on the importance of time management.

Bast gave tips on being productive and managing time smartly by delegating and prioritising one's time and energy. He highlighted the importance of scheduling time-blocked to-do lists and notes to help eliminate unnecessary tasks and reducing interruptions. In addition, speakers talked about how efficient and regular communication helps build trust between team members and saves time and energy.

On day three, Shubha Tole, Professor, Tata Institute of Fundamental Research (TIFR), Mumbai; Shalini Arya, Assistant Professor, Institute of Chemical Technology, Mumbai; Yoko Shimpuku, Professor, Hiroshima University, Japan; and Gitanjali Yadav, Faculty, University of Cambridge, UK, discussed the value of having a positive lab culture.

Tole emphasised that choosing the right mentor to do a PhD would significantly impact one's whole experience and work. A good and positive lab culture is a must to be able to work happily and efficiently. In addition, one should be passionate and compassionate with one's approach while dealing with other lab members and staff, Tole said.

Be clear of what you do not want, even if you do not know what you want – Smita Jain, Executive Director, IndiaBioscience

The next day focused on the theme of "flexibility during unpredictable circumstances". The speakers included Shobhana Sharma, Retired Professor, TIFR, Mumbai; Robert Lepenies, Research Scientist, Helmholtz Centre for Environmental Research, Germany; Magdalena Skipper, Editor-in-Chief, Nature London, UK; and Vandana Vinayak, Associate Professor, Dr Harisingh Gour Vishwavidyalaya, Sagar, India.

The speakers discussed how flexibility was not just about responding to changing events quickly. It also involves responding to the different needs of the people in the workspace. Being adaptive and welcoming new ideas brings optimism and growth with the chance of learning something new. The speakers emphasised the importance of honesty, transparency, and empathy.

On day five, Shahid Jameel, Director, Trivedi School of Biosciences, Ashoka University, Sonipat; Smita Jain, then Executive Director, IndiaBioscience, Bengaluru; R.K. Kohli, Vice-Chancellor, CUPB, and Monisha Dhiman, Professor, CUPB, spoke about career and productivity.

"Be clear of what you do not want, even if you do not know what you want," said Jain. The speakers discussed how being decisive requires both courage and intelligence. It is essential to base conclusions on data and evidence and to review decisions as one progresses. Jain also highlighted the difference between a job and a career: "a job is the work one performs to earn money to support one's basic needs while a career is an individual's long-term professional journey through learning, work, and passion." Jameel said that "Productivity is directly proportional to the effective, productive time spent in the lab" for a research scholar.

Management is about taking control; leadership is about giving control – Alok Dhawan, Director, CSIR

On day six, L.S. Shashidhara, Professor, Ashoka University, Sonipat; Alok Dhawan, Director, CSIR-Indian Institute of Toxicology Research, and Mona Khoury-Kassabri, Professor, The Hebrew University of Jerusalem, Israel, spoke about the importance of critical thinking.

A critical thinker who aspires to be a leader in science should have an eye for observation and be an abstract thinker, they said. One should believe nothing until it gets defined by one's understanding. Dhawan said, "Management is about taking control; leadership is about giving control."

On the seventh and final day of the workshop, Dipankar Chatterji, Former-President, IASc, Bangalore; Ramarao Poduri, Retired professor, CUPB, and Shekhar C Mande, Director General, Council of Scientific and Industrial Research, New Delhi, discussed factors involved in risk-taking.

They pointed out that a positive risk element can positively affect one's project and its objectives, so one should be open to learning and making mistakes. Chatterji advised to never saying no to teaching.

The speakers also touched upon a few other topics such as:

• The need for better opportunities for women in science,
• The importance of cross-cultural communication,
• Mentorship networks,
• The need for better transparency and clarity in communication and,
• The importance of collective leadership.

Overall, the experts highlighted that a leader in science should aim high and have a big vision. Leaders should work equally on honing technical and soft skills; they should be compassionate and helpful, build teamwork skills to sustain excellence with relevance in an organisation.

India carries a high disease burden and mortality rate of malaria. Karnataka is one of the states with a high prevalence of the disease. In the state, Mangaluru city has the highest number of malaria cases. Until a few years ago, the case reporting was done manually by field workers who visited, recorded, and reported the cases, after which measures to contain the spread of the disease would be implemented.

However, in 2014, Mangaluru witnessed a massive spike in malaria. In order to combat the situation, B Shantharam Baliga, Professor Emeritus, Kasturba Medical College, Mangalore, conceptualised a digital surveillance system for malaria. His team, along with Naren Koduvattat, Director, i-POINT Consulting, Mangaluru, developed an indigenous software tool called the Malaria Control System (MCS) to monitor malaria cases in the city. The team reports that five years post the digitisation, the annual malaria incidences in the city reduced by 83% and further to 90% to date (Fig. 1).

Baliga says, “Malaria is endemic to Mangaluru since 1995. In the manual surveillance system, little or no action would be taken most of the time because of the gap between incidence and reporting of the case.” The team realised the urgency of the matter. “We had a clear intervention protocol and a good workforce in place. But the flow of information was far from satisfactory,” adds Koduvattat.

So, in October 2014, the team collaborated with Mangaluru City Corporation, Mangaluru, District Health and Family Welfare Department, and the Indian Council of Medical Research - National Institute of Malaria Research (Field Unit), Bengaluru, and initiated the use of MCS to monitor malaria cases in Mangaluru.

MCS is an android-based software designed for the stakeholders in a malaria control programme – the diagnosticians, field workers and the civic authorities. The software is installed in a hand-held tablet whose geographical location is linked with a web-based reporting system. All the stakeholders can enter data into the application even without internet connectivity. The device then uploads the information whenever the internet connection becomes available.

Hospitals and diagnostic centres use the application to report malaria cases along with the patient’s address. Healthcare workers ‘open’ a case and file reports. Field workers access the information, visit the patient’s house, spot and upload images and location of nearby potential mosquito breeding sites to the application. The software then tabulates these data into a spreadsheet, which is accessible to health administrators. In the meantime, the patient receives treatment as per the malaria treatment protocols. The case ‘closes’ once the treatment is complete (on the 14^th day of the treatment).

The city’s civic body completely digitised the monitoring by September 2015. The reporting speeds were immediately apparent. The team noticed that 89% of the new cases were reported within 48 hours of the incidence — a stark contrast to manual reporting, which would take up to a month earlier. The following year saw a steady increase in reported cases indicating that digitised monitoring fostered better reporting.

The researchers also tracked the rate of positive cases and the disease burden of a location (determined by a parameter called Annual Parasite Incidence, API). Over the years, the annual number of malaria incidences decreased as now, the field workers could implement containment measures (such as arresting mosquito breeding sites) within a day or two of detecting a case. The researchers found that the API reduced by 80% or more in 43 municipal wards (Fig. 1).

“MCS has given some promising results in the district,” says Aparna Sen Chaudhary, Medical Consultant and a public health professional who was not involved in the study. “Such software could help curb malaria in India as it allows for the micro-level implementation of anti-malaria activities.” She adds that the researchers can use data of the reported cases to build models that predict cases on a fortnightly, monthly or annual basis to guide administrative actions.

Baliga says that MCS is a versatile tool that can be used to monitor other diseases like chikungunya or dengue and even those like COVID-19.

The authors also posit that information technology systems like MCS are essential to maintain continuity of control measures, even when civic bodies are compelled to divert resources to fight new battles.

Since its inception in 1958, the American Society of Hematology (ASH) has been pivotal in developing hematology as a discipline of scientific and clinical importance. As blood disorders plague millions around the world with some of the most serious unmet medical needs, ASH established the ASH Global Research Award in 2018 to nurture future leaders in the field of hematology through global collaborative research.

The ASH Global Research Award supports early-career scientists and doctors in the field of hematology during the progression between their training and establishing independent careers.

Neeraj Jain, the first Indian recipient of this award in 2020 and a Ramalingaswami Re-entry Fellow at CSIR-Central Drug Research Institute, Lucknow, shares his insights on the intricacies of this award. He says, “First, the award prioritizes a project’s novelty, whether it is doable at an applicant’s institute and home country, and if the desired resources are available. Second, ASH examines the applicant’s candidature to undertake the proposed project. I am presently trying to identify molecular signatures in Indian B-cell lymphoma patients. In my case, ASH had expressed concerns if I will have sufficient clinical samples for my work and what is my alternative plan if my project does not go as expected.”

The ASH Global Research Award is a career-development award that supports the awardees and not the institutions they work at - Neeraj Jain

The award is open to applicants around the world except for US and Canadian citizens (who are eligible only upon fulfillment of specific criteria) and investigators employed by pharmaceutical or biotechnology companies. An applicant must have an MD, PhD or MD-PhD. At the time of application, MD and MD-PhD applicants must be within 16 years of MD graduation, and PhD graduates must have at least one year and not more than 10 years of postdoctoral experience.

The award tenure can last anywhere between six to thirty six months. For projects of up to 12 months and those exceeding that, applicants can request up to $100,000 and $150,000 respectively. The award supports projects and mentorship in basic or translational research, patient-oriented clinical research, outcomes-based research and clinical trials. Applicants may propose support for instruments, manpower, consumables and other essentials for their research.

The electronic application occurs in two steps: (1) Submission of a Letter of Intent (LOI) and (2) Selected candidates are invited to submit a full proposal.

For the LOI, applicants need to submit a narrative of the proposed project, initial plans of the mentorship team, funding amount, project timeline, applicant’s career details and plans, and curriculum vitae. Vonnie Calemine, Awards Program Manager at ASH says, “The LOI should be thorough and well thought out. It is important to emphasize what impact this project will have on science, regional health and the applicant's career. If a person is invited to submit the full application, we highly recommend creating it with the assistance of their local and global mentors, since not all full applications are funded.”

In order to apply, the applicants must have a local mentor in their country of residence and a global mentor outside their country of residence, one of whom must be an ASH Active or International member. ASH also helps invited applicants for the second step, to identify mentors if they have not already done so.

About the award, Neeraj says, the ASH Global Research Award is a career-development award that supports the awardees and not the institutions they work at. He adds that projects with novelty that propose to answer broad confounding questions in blood disorders including blood cancers and other associated genetic diseases have higher chances at being successful.

The deadline for this year’s Letter of Intent call is 31 August 2021.

Land plants live in dual environments: a part above the soil surface, absorbing sunlight and air, while the other part is underground in low oxygen conditions. These differing conditions present these plants with different stresses above and below the ground. Land plants have therefore evolved different coping mechanisms to survive in these contrasting environments.

A team of researchers led by R Sankaranarayanan at the CSIR-Centre for Cellular and Molecular Biology, Hyderabad, has found that archaea, the earliest microbial ancestors of multicellular life on earth, could have helped land plants to survive the stresses they face underground. The researchers found that land plants and archaea both have a common protein called DTD2 that is involved in protein synthesis. They find that DTD2 helps in selecting the right kind of amino acids for protein synthesis in low-oxygen conditions.

Amino acids are the building blocks of proteins, and plants absorb them from the soil. But soil is abundant with two forms of amino acids, called the D and L forms. Despite this, living cells build proteins only using L-amino acids. Accidental addition of D-amino acids into proteins can kill the cells, and hence, must be avoided. Bacteria, fungi and animals use another protein called DTD1 to identify the D-amino acids attached to protein synthesis machinery and chop them off.

When plant root cells respire in low-oxygen conditions, a chemical called acetaldehyde is formed, which affects their protein synthesis machinery. In the presence of acetaldehyde, DTD1 fails to identify the wrongly attached D-amino acids. However, DTD2 can pitch in to do the job. “Using mass spectrometry and enzymatic assays, we show that DTD2 can nullify the effect of acetaldehyde on protein synthesis machinery as well as remove the D-amino acids,” says Mazeed Mohd, first author of the study.

The researchers searched for DTD2 gene sequences across living organisms. “We find the DTD2 genes only in archaea, land plants and their ancestors. It is missing in other life forms,” says Raghvendra Singh, joint first author of the study. Given that the first land plants emerged three billion years after archaea, the team was surprised to find a protein that is common only between them. They propose two possibilities to explain this. If the DTD2 gene came to all eukaryotes (organisms with nucleated cells, e.g. plants, animals, fungi and protozoa) from archaea, then all of them except the plants have lost the gene. The other option is that archaea directly transferred the gene only to land plants or their ancestors.

The researchers reason that the latter possibility – of archaea transferring the gene to plants - is more probable for two reasons: i) It is easier to explain one-gene transfer event than multiple gene-loss events, ii) Archaea and land plant ancestors are found in overlapping ecosystems, which can explain gene transfer due to their physical proximity.

A type of algae called the streptophyte algae are believed to be the ancestors of land plants. Archaea and streptophyte algae both grow in bogs rich in methane and low on oxygen. “We think that archaea shared its DTD2 gene with streptophyte algae as a result of their cohabitation. As land plants evolved from streptophyte algae, they inherited the DTD2 from the algae,” says Sankaranarayanan.

Umesh Varshney, Professor, Indian Institute of Science, Bengaluru, who studies protein synthesis in bacteria and who was not associated with this study, comments on the importance of the study. He says, “This study raises questions of fine mechanistic details on land plants’ evolution and addresses them with well-designed experiments. The study presents the physiological relevance of DTD2 and brings out its importance in the evolution of land plants.”

In an exciting breakthrough, a team of scientists led by Ellora Sen at the National Brain Research Centre (NBRC), Manesar, has found that glycyrrhizin, an active ingredient in the roots of a commonly used herb Mulethi or liquorice (botanical name Glycyrrhiza glabra) shows therapeutic potential for COVID-19.

Glycyrrhizin is known to have natural anti-inflammatory properties. The herb, known as Yashtimadhu in Sanskrit, is widely used in the traditional Indian medicine system of Ayurveda to treat respiratory illnesses.

In their preliminary experiments, the researchers found that glycyrrhizin suppresses the ‘cytokine storm’ in human lung epithelial cells expressing SARS-CoV-2 viral proteins, and inhibits SARS-CoV-2 replication in infected cultured cells, thereby reducing the severity of the infection.

When SARS-CoV-2 infects human cells, the body’s immune system activates to combat the viral onslaught by releasing cytokines. In their defence against the virus, the cytokines cause inflammation in the infected cells.

In the case of a severe infection, the immune cells respond rapidly by releasing a ‘storm of cytokines’ to suppress the viral replication. However, existing literature shows that the uncontrolled release of cytokines can turn out to be detrimental to the lung cells, as it causes severe inflammation and fluid accumulation in the lung tissues. This condition may lead to acute respiratory distress, cell death, and eventually, organ failure.

In this study, the researchers expressed SARS-CoV-2 viral proteins in human lung cells growing in laboratory dishes, which resulted in inflammation in these cells. On further examination, they discovered that the viral proteins caused an enhanced release of a protein called HMGB1 outside the cells, triggering inflammatory cell death.

The team then treated these cells with glycyrrhizin to understand its potential in alleviating the detrimental effects of cytokine release. They found that the inflammatory death of lung cells could be rescued by glycyrrhizin. Further examination revealed that glycyrrhizin inhibited the release of HMGB1 and prevented the activation of macrophages – the immune cells primarily responsible for producing cytokines and consequently, the cytokine storm.

Besides, the researchers also found that glycyrrhizin dampened the release of ferritin from the macrophages. Ferritin is an iron storage protein that has immune-suppressive functions, and ferritin levels increase in the blood in case of acute infection.

Further, the researchers infected Vero-E6 cells (a type of cell lines used to grow viruses in laboratory conditions), with SARS-CoV-2 virus. They treated these cells with increasing concentrations of glycyrrhizin to see if it could protect the cultured cells from infection. They found that depending on its dose, glycyrrhizin inhibited the viral replication by up to 90%, without causing any significant toxicity to these cells.

Presently, patients with severe COVID-19 symptoms (who require supplemental oxygen) are treated with combination therapy of antivirals such as Remdesivir and anti-inflammatory drugs to inhibit viral replication and manage the disease symptoms. “The effect of glycyrrhizin in bringing down SARS-CoV-2 viral load is comparable to that of Remdesivir. Additionally, it also functions as an anti-inflammatory agent,” says Sen, principal investigator of the study. Sen adds that their observations also reinforce existing studies on the SARS-associated coronavirus and influenza virus where glycyrrhizin inhibits viral replication.

G L Krishna, Ayurvedic Doctor and independent researcher from Bengaluru, says, “Ayurveda provides a unique and holistic approach to disease treatment with the interventions being supportive of the body’s self-healing processes. It is the case with COVID-19 as well.” He emphasises that natural herbs like mulethi have minimal or no potential side effects, the advantage of which cannot be undermined.

Ulf Andersson, Paediatric Rheumatologist, Karolinska University Hospital, Stockholm, whose decades of work on HMGB1 has contributed significantly to its understanding, says, “As glycyrrhizin prevents hyper inflammation by binding directly to HMGB1 and inhibits SARS-CoV-2 replication - both central events responsible for the dramatic course in severe COVID-19 - it, therefore, deserves to be studied in clinical therapeutic trials in COVID-19.”

Sen says, “It is time we acknowledge what Ayurveda has to offer to us. We are confident that the compound glycyrrhizin can be a potential therapeutic option in COVID-19 patients.”

Viruses are constantly mutating, and that is how they evolve and adapt to survive. Viral mutations arise due to the error-prone system they use for copying and propagating their genome. Mutating agents present in the immediate environment can also influence the virus to change. The mutations occurring in SARS-CoV-2 have been a cause of concern. Hence, studying these mutations is all-important to remain aware of emerging dominant variants.

A collaborative study led by Ranadhir Chakraborty, Professor, North Bengal University, Siliguri, and Wriddhiman Ghosh, Associate Professor, Bose Institute, Kolkata, analysed SARS-CoV-2 genomes deposited till 21 August 2020 in the global viral genomic database (GISAID).

The researchers tried to understand the trends in terms of the nature, frequency, and distribution of viral mutations across 71703 viral sequences reported from countries around the world and compared them with the genetic sequence of the earliest SARS-CoV-2 strain reported from Wuhan, China. The team used computational tools to track and compare mutations in the viral genome.

The researchers then extended the analysis to key viral genes. Their investigation revealed the predominance of certain ‘missense’ mutations among the genes that code for viral envelope structures like the spike protein. Missense mutations have the potential to alter the function of a protein by replacing an amino acid of a protein with an incorrect one. These changes may or may not affect the performance of the protein. And if the structural change turns out to provide an advantage to the virus for surviving in challenging situations, then these specific mutations get selected over successive generations to become the dominant strains in a viral community.

The researchers observed that the structural proteins known as ORF3a and ORF7a were most prone to mutation. While ORF3a has a role in regulating virulence and transmissibility, ORF7a is involved in modulating the human immune response.

Chakraborty says, “This implies vigorous molecular manoeuvring by the virus to augment its virulence potentials, escape human immunity, and ensure enhanced transmissibility.” Their observations were later given credence when several such missense mutations in the spike protein gene were identified in the emerging variants with increased transmissibility like the UK strain (B.1.1.7) and the South African variant (501Y.V2), adds Chakraborty.

The researchers then analysed the mutations at the single nucleotide level. Nucleotides are the building blocks of genes and come in four varieties – cytidine ( C), uridine (U), guanosine (G) and adenosine (A). Single nucleotide mutations usually replace one type of nucleotide with another. The researchers observed that there was a predominance of two specific nucleotide conversions. One of these was a C to U conversion, and the other was a G to U.

The researchers say that one driving factor for the high occurrence of these conversions could be due to the errors occurring while the virus replicates inside a human cell. In a few preliminary observations, the researchers also noticed that C-U conversions occurred in environments that had a high content of UV irradiations and chemicals like bisulfites. They suggest that indiscriminate use of germicidal and sanitising agents could possibly act as an external trigger for mutations.

Bornali Bhattacharjee, Ramanujan Fellow, National Institute of Biomedical Genomics, Kalyani, West Bengal, who was not connected with this study, comments that “The higher frequencies of C-U and G-U transitions as observed in this article have also been observed by our group and a few others.”

This study brings attention to the need for multifaceted surveillance of the emerging viral variants of the SARS-CoV-2 genome and their plausible triggers to stay a step ahead in tracking high-frequency mutations.