25-Aug-2022: Newly identified gene could be clue to treatment of fungal infection in immuno-compromised patients
A newly identified gene can hold the key to prevent fungal infection Candidiasis that often affects intensive-care unit (ICU) patients, cancer patients and patients receiving immunosuppressive therapy.
The gene called CSA6 has been identified in Candida albicans a fungal species infamous for causing high rates of morbidity and mortality under certain immuno-compromised conditions such as AIDS or during cancer treatment. The fungal species residing in mucosal linings of the gastrointestinal and urogenital tract of healthy individuals turns into a pathogen under immuno-compromised conditions breaching the host defense causing superficial as well as life-threatening systemic infection.
In a recent collaborative study between Professor Kaustuv Sanyal’s group at Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore, India and Christophe d’Enfert’s group at Institut Pasteur, Paris, France (Jaitly et al, 2022), authors carried out a large-scale screen to identify regulators of chromosome stability in C. albicans, a clinically relevant fungal model system.
The authors from JNCASR, an autonomous institute of Department of Science and Technology (DST), individually screened the effect of overexpression of more than a thousand genes of C. albicans on genome stability and were successful in identifying a set of six chromosome stability (CSA) genes that are important for maintaining genome integrity. While five of the CSA genes identified in the study are known to be important for cell division in other species, the sixth CSA gene, named CSA6 encoded for a protein that is essential for viability in C. albicans. They found that Csa6 was a critical regulator of cell cycle progression wherein both overexpression and deletion of Csa6 lead to reduced growth of C. albicans cells.
The study published in the journal Nature Communications represents the first-ever report of such an extensive screen in the human fungal pathogen C. albicans. It identifies and elucidates the functions of a novel regulator of chromosome stability that is exclusively present in a group of medically relevant human fungal pathogens. Besides, it also provides a systematic scheme for identifying genes whose products may serve as potential therapeutic interventions for fungal infections by posing lesser adverse effects on humans. Hence, small molecule modulators that alter expression levels of the gene called Csa6 offer potential avenues for treatment with no side effects in humans.
19-Jul-2022: New Strain of Rice
Budget sanctioned for Indian Agricultural Research Institute (IARI) is Rs. 98.05 lakhs. This work is done through CRISPR-Cas9 mediated Genome Editing technology. The research work is carried out with the approval of Institutional Biosafety Committee (IBSC) constituted by Department of Biotechnology (DBT), Government of India as per Rules 1989 under Environment (protection) Act 1986.
Ministry of Environment, Forest and Climate Change vide its OM F.No. C-12013/3/2020-CS-III, dated 30th March, 2022 has exempted the Genome Edited plants in the categories of SDN1 and SDN2, which are free of exogenously introduced DNA, from the provisions of Rules 7-11 (both inclusive) of the Rules 1989.
Department of Biotechnology, Govt. of India has notified “Guidelines for the Safety Assessment of Genome Edited Plants, 2022” vide OM File No. PID-15011/1/2022-PPB-DBT dated 17.5.2022.
Genome edited lines is expected to be available for field evaluation by Kharif 2024 and for general cultivation during 2026 after two years of field testing.
13-Jul-2022: Scientists develop novel mechanism to inactivate SARS-CoV-2 by blocking their entry to cells & reducing infection ability
Researchers have reported the design of a new class of synthetic peptides that can not only block the entry of SARS-CoV-2 virus entry into cells but also clump the virions (virus particles) together, reducing their ability to infect. This novel approach provides an alternative mechanism to render viruses like SARS-CoV-2 inactive, promising a new class of peptides as antivirals.
The rapid emergence of new strains of the SARS-CoV-2 virus has diminished the protection offered by COVID-19 vaccines calling for new approaches to prevent infection by the virus.
It is known that protein-protein interaction is often like that of a lock and a key. This interaction can be hampered by synthetic peptide that mimics, competes with, and prevents the ‘key’ from binding to the ‘lock’, or vice versa. Scientists at the Indian Institute of Science (IISc), in collaboration with researchers from the CSIR-Institute of Microbial Technology, have exploited this approach to design peptides that can bind to and block the spike protein on the surface of SARS-CoV-2 virus. This binding was further characterised extensively by cryo-electron microscopy (cryo-EM) and other biophysical methods.
The research was supported under the COVID-19 IRPHA call of SERB Science and Engineering Research Board (SERB), a statutory body of Department of Science and Technology (DST).
The designed peptides are helical, hairpin-shaped, each capable of pairing up with another of its kind, forming what is known as a dimer. Each dimeric ‘bundle’ presents two ‘faces’ to interact with two target molecules. In the study published in Nature Chemical Biology, the researchers hypothesised that the two faces would bind to two separate target proteins locking all four in a complex and blocking the targets’ action. The team decided to test their hypothesis by using a peptide called SIH-5 to target the interaction between the Spike (S) protein of SARS-CoV-2 and ACE2 protein, the SARS-CoV-2 receptor in human cells.
The S protein is a trimer – a complex of three identical polypeptides. Each polypeptide contains a Receptor Binding Domain (RBD) that binds to the ACE2 receptor on the host cell surface. This interaction facilitates viral entry into the cell.
The SIH-5 peptide was designed to block the binding of the RBD to human ACE2. When a SIH-5 dimer encountered an S protein, one of its faces bound tightly to one of the three RBDs on the S protein trimer, and the other face bound to an RBD from a different S protein. This ‘cross-linking’ allowed the SIH-5 to block both S proteins at the same time. Under cryo-EM, the S proteins targeted by SIH-5 appeared to be attached head-to-head, and the spike proteins were being forced to form dimers. Subsequently, the researchers showed that SIH-5 inactivated the viruses efficiently by cross-linking the spike proteins from different virus particles.
The team consisting of B Khatri, I Pramanick, SK Malladi, RS Rajmani, P Ghosh, N Sengupta, R Varadarajan, S Dutta and J Chatterjee from Indian Institute of Science (IISc), R Rahisuddin, S Kumar, N Kumar, S Kumaran and RP Ringe from CSIR-Institute of Microbial Technology, tested the peptide for toxicity in mammalian cells in the lab and found it to be safe. When hamsters were dosed with the peptide and subsequently exposed to a high dose of SARS-CoV-2, they showed decreased viral load as well as much less cell damage in the lungs compared to hamsters exposed only to the virus, demonstrating the promise of this class of peptides as antivirals.
The researchers believe that with minor modifications and peptide engineering, this lab-made miniprotein could inhibit other protein-protein interactions as well.
30-Mar-2022: Over two lakh genome and DNA sequencing of COVID-19 done till 23rd March 2022
Union Minister of State (Independent Charge) Science & Technology; Minister of State (Independent Charge) Earth Sciences; MoS PMO, Personnel, Public Grievances, Pensions, Atomic Energy and Space, Dr Jitendra Singh said that the Indian SARS-CoV-2 Genomics Consortium (INSACOG) being coordinated by the Department of Biotechnology (DBT), as on 23rd March 2022 has sequenced 2,01,373 SARS-CoV-2 genomes.
In a written reply to a question in the Lok Sabha today, Dr Jitendra Singh said, the Department of Biotechnology (DBT), based on extensive scientific deliberations, initiated an integrated response to overcome the unprecedented COVID-19 pandemic, in alignment with R&D Blueprint of the World Health Organization (WHO).
He said, DBT along with its public sector undertaking Biotechnology Industry Research Assistance Council (BIRAC) launched ‘DBT-BIRAC COVID-19 Research Consortium’ whereby, Research and Development projects were supported across the thematic areas of vaccines and supporting ecosystem, diagnostics and facilities for scale-up, therapeutics, drug repurposing & supporting ecosystem, and other biomedical interventions.
The Indian SARS-CoV-2 Genomics Consortium (INSACOG) started jointly by Department of Biotechnology and Ministry of Health and Family Welfare in collaboration with Council of Scientific and Industrial Research and Indian Council of Medical Research with primary aim to expand whole genome sequencing of SARS-CoV-2 virus across the nation. Under National Biopharma Mission and Mission COVID Suraksha, the Department has enabled support for pre-clinical development of COVID-19 vaccine candidates and scale-up of manufacturing of COVID-19 diagnostic kits, facilities for animal challenge studies, facilities for immunogenicity assays, clinical trial sites etc.
The Minister informed that a total of 17 COVID-19 Bio-repositories have been notified by the Government of India. These are set up at laboratories of Department of Biotechnology (DBT), Council of Scientific & Industrial Research (CSIR) and Indian Council of Medical Research (ICMR). These COVID-19 Bio-repositories established at:
- ICMR-National Institute of Virology, Pune
- ICMR-National Institute of Virology Field Unit, Bangalore
- ICMR-National Institute of Virology Field Unit, Kerala
- ICMR- National Institute of Cholera and Enteric Diseases, Kolkata
- ICMR-National Institute for Implementation Research on Non-Communicable Diseases, Jodhpur
- ICMR- National Institute of Malaria Research, Delhi
- ICMR- National Institute of Epidemiology, Chennai
- ICMR- National Institute for Research in Reproductive Health, Mumbai
- ICMR-Regional Medical Research Centre, Dibrugarh
- NCR Biotech Science Cluster Translational Health Science and Technology Institute and Regional Centre for Biotechnology, Faridabad
- Institute of Life Sciences, Bhubaneswar
- Institute for Stem Cell Science and Regenerative Medicine, Bengaluru
- National Centre for Cell Science, Pune
- DBT funded Biorepository – Institute of Liver and Biliary Sciences, New Delhi
- CSIR- Institute of Genomics and Integrative Biology, New Delhi
- CSIR- Centre for Cellular & Molecular Biology, Hyderabad
- CSIR - Institute of Microbial Technology, Chandigarh
2-Dec-2021: More than one lakh SARS-CoV-2 genomes sequenced till November 2021 for COVID-19
Union Minister of State (Independent Charge) Science & Technology; Minister of State (Independent Charge) Earth Sciences; MoS PMO, Personnel, Public Grievances, Pensions, Atomic Energy and Space, Dr Jitendra Singh said that more than one lakh SARS-CoV-2 genomes sequenced till November 2021 for COVID-19.
In a written reply to a question in the Rajya Sabha today, the Minister informed that the Indian SARS-CoV-2 Genomics Consortium (INSACOG) being coordinated by the Department of Biotechnology (DBT), as on 25th November 2021 has sequenced 1,02,880 SARS-CoV-2 genomes.
A total of 17 COVID-19 Bio-repositories have been notified by the Government of India on 23-05-2020. These are set up at laboratories of Department of Biotechnology (DBT), Council of Scientific & Industrial Research (CSIR) and Indian Council of Medical Research (ICMR).
On the question of the number of COVID-19 Bio-repositories and samples that were made available to academia and industry for product development, the Minister gave the following details:
DBT funded Biorepository at ILBS, New Delhi has shared 1299 samples with academia. ILS, Bhubaneswar has provided samples from the biorepository to 18 research and development projects. NCCS, Pune has shared a total of 124 samples so far with academia and industry. InSTEM, Bangalore has shared a total of 363 samples so far with academia and industry. NCR Biotech Science Cluster Translational Health Science and Technology Institute & Regional Centre for Biotechnology, Faridabad have shared a total of 20890 samples so far with academia and industry.
CSIR-CCMB shared about 200 samples with incubatees at CCMB- Atal Incubation Centre for development of interferometry antibody detection, 200 samples for development of in house Elisa based assays, and about 250 samples were shared for development of RT-PCR assays. Samples have also been utilized for testing and validating technologies/ products developed by industries. CSIR-IGIB Bio-repository has been used to help testing and validation of diagnostic products. CSIR-IMTECH made available 15 samples for academic research in IMTECH and 30 samples were shared with PGIMER, Chandigarh for quality control analysis of RT-PCR testing.
23-Aug-2021: Indian Scientist Partners with BRICS Group to Setup Network of Genomic Surveillance and Study the Overlap of SARS-CoV-2 with tuberculosis
Department of Biotechnology, Ministry of Science and Technology, Government of India in collaboration with BRICS countries is implementing SARS-CoV-2 NGS-BRICS consortium and multi centric programme to study the impact of severe COVID-19 conditions on TB patients.
The SARS-CoV-2 NGS-BRICS consortium is an interdisciplinary collaboration to advance COVID-19 health-relevant knowledge and to contribute to improvements in health outcomes. The consortium will accelerate the translation of genomic data leading to clinical and public health research and interventions from clinical and surveillance samples by utilising the high-end genomic technologies, and epidemiologic and bioinformatics tools for future use in diagnostic assays and tracking transmission dynamics of COVID-19 and other viruses. The Indian team consists from National Institute of Biomedical Genomics (Professor Arindam Maitra, Professor Saumitra Das, Dr Nidhan K Biswas), Centre for DNA Fingerprinting and Diagnostics (Dr Ashwin Dalal) and Indian Institute of Science (Dr Mohit K Jolly) along with National Laboratory for Scientific Computation - LNCC/MCTI (Dr Ana Tereza Ribeiro de Vasconcelos) from Brazil, Skolkovo Institute of Science and Technology (Professor Georgii Bazykin) from Russia, Beijing Institute of Genomics, Chinese Academy of Sciences (Professor Mingkun Li) from China and University of KwaZulu-Natal (Professor Tulio de Oliveira) from South Africa will participate in this consortium.
The second multi centric programme consists of an interdisciplinary team of researchers from India, Brazil and South Africa who would investigate the impact of severe COVID-19 on transient peripheral immunosuppression and lung hyperinflammation conditions in TB patients for epidemiology and comorbidity. This team consists of National Institute of Research in Tuberculosis (Dr. Subash Babu, Dr. Anuradha Rajamanickam, Dr. Banurekha Velayutham and Dr. Dina Nair) from India, Lapclin-Tb/ Inifiocruz (Dr. Valeria Cavalcanti Rolla), IMU, LIB, MONSTER/ IGMFIOCRUZ (Dr. Bruno de Bezerril Andrade), LAPCLIN-TB/ INIFIOCRUZ (Dr. Adriano Gomes da Silva) and LBB/ INI-FIOCRUZ (Dr. Maria Cristina Lourenço) from Brazil and University of the Witwatersrand, Johannesburg, South Africa (Dr. Bavesh Kana, Dr. Bhavna Gordhan, Dr. Neil Martinson and Dr. Ziyaad Waja) from South Africa.
This collaborative study is expected to provide valuable co-morbidity data pertaining to pulmonary TB patients with or without COVID-19 co-infection that is expected to be generated for better disease management.
Dr. Renu Swarup, Secretary, Department of Biotechnology remarked that the department has taken small steps in the right direction towards collaboration with BRICS countries. Dr. Renu Swarup also remarked that the Department plans to expend the BRICS programme.
29-May-2020: Researchers culture novel coronavirus, may help in drug testing and vaccine development
The Centre for Cellular and Molecular Biology (CCMB) has established stable cultures of coronavirus (SARS-CoV-2) from patients’ samples. Virologists at CCMB have isolated infectious viruses from several isolates. The ability to culture the virus in lab enables CCMB to work towards vaccine development and testing of potential drugs to fight COVID-19.
Novel coronavirus enters human cell by binding with the ACE-2 receptor on the cell surface. Not all cells have ACE-2 receptors. Human epithelial cells in the respiratory tract copiously express ACE-2 receptors, causing respiratory disease in the infected patient. However, we cannot grow human epithelial cells in lab. “Currently, primary epithelial cells generated from human origins do not grow for many generations in labs, which is key to culturing viruses continuously. At the same time, the labs that are growing the virus need an ‘immortal’ cell line”, says Dr Krishnan H Harshan, Principal Scientist, CCMB. They use Vero cells (kidney epithelial cell lines from green African monkey), which express ACE-2 proteins and carry a cell division that allows them to proliferate indefinitely.
But why cultivate a dreadful germ? If we culture a large amount of the virus and inactivate them, then it can be used as inactivated virus vaccine. Once we inject the inactivated virus, the human immune system triggers the production of germ-specific antibodies. One can inactivate the virus by heat or chemical means. The inactivated virus can trigger antibody response, but does not infect and make us sick as they cannot reproduce.
For the development of antibodies or antidots, virus cultures are important. Inactivated viruses can trigger antibody response in other mammalian hosts in addition to humans. Various such hosts are currently under test for their efficiency of antibody response. Such antibodies generated in these non-human hosts can be purified, processed and collected. The antibodies can be used as therapeutic intervention for patients suffering from the infection. Such antibodies can trigger antiviral response upon injection into humans and have the potential of limiting the infection. Administering antibodies does not provide immunity like a vaccine does, but can be considered as anti-dotes against the virus.
These cultures may also be helpful in the process of drug screening. Potential drugs can be tested against the virus in a test-tube for their efficacy.
“Using the Vero cell lines to grow the coronavirus, CCMB is now in a position to isolate and maintain viral strains from different regions. We are working towards producing viruses in huge quantities that can be inactivated, and used in vaccine development and antibody production for therapeutic purposes”, says CCMB Director, Dr Rakesh Mishra. CCMB has also started testing potential drugs with other partners such as the Defence Research Development Organisation (DRDO) using this viral culture.
“We hope that such systems are replicated at multiple research institutes and private companies to become a useful resource in the fight against this pandemic as well as for future preparedness”, said Dr Mishra.