DBT/WT India Alliance

Overview

The Biomedical Research Career Programme, also called the DBT/WT India Alliance, is a partnership between the Department of Biotechnology (DBT) Government of India and the Wellcome Trust (WT), UK. The founding principle of this programme was to establish a research ecosystem comparable to the best in the world in biomedical sciences, clinical and public health research and propel our researchers to leadership positions in Biomedical and Life Science Research. The programme awards Fellowships across career stages and interdisciplinary collaborative Grants, addressing public health challenges in the country.

The DBT/WT India Alliance (India Alliance) funds research endeavours of the highest scientific and ethical quality for the development of resources and advancement of knowledge for maximum benefit. The funding portfolio reflectsthe shared vision of DBT and WT to nurturing excellence in basic and clinical research, and establishing an enabling research ecosystem in India. India Alliance boosts research capacity through research fellowships, attracting scientists to establish competitive programmes in India and fostered research on key public health challenges through collaborative grants in clinical and public health, involving a minimum of three partnering institutions. India Alliance has actively worked to bring more diversity and inclusion into science and health, and fund urgently needed research to drive action, translation, and policy change.

Key objectives include

• Attracting globally competitive researchers in biomedical and clinical sciences, to establish research programmes in institutions and universities in India and support professional aspirations for a fulfilling research career.
• Fund research of international standard by various programmes that support independence and career progression of outstanding early career researchers in India.
• Support open, equitable and ethical research environments through programmes creating awareness and training in allied careers in Research Management, Science Administration, Regulatory Processes etc.
• Expanding the footprint of India Alliance activities to new locations in the country and under-served research communities.

Brief of Major initiatives taken

• Calls for proposals were made for the following programmes and applications processed via peer review and shortlisting for interview

• Selection Committee meetings were convened in February 2023, July 2023, December 2023 and February 2024.
• The India Alliance Annual Conclave was held from July 13-15, 2023 in Hyderabad. The conclave included scientific talks by Awardees and invited speakers.
• Reviews to monitor progress of relevant awardees (In year 2-2.5 and year 4-4.5), by committee members and external experts was also undertaken during the Conclave.

Notable Outcomes and Achievements of the program.

A. Recognition: Several DBT/WT India Alliance Fellows have received national and international recognition. (Figure 1: IA Fellows image)

B. Arun Shukla, a Senior Fellow with DBT/WT India Alliance and a Professor at the Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur was awarded the Infosys Prize in Life Sciences, 2023 for his work on G-Protein-Coupled Receptors (GPCRs). The GPCRs constitute a large family of drug targets in our body including drugs for heart failure, high blood pressure, depression and different cancers. Arun Shukla has led the field, creating new knowledge about GPCRs for the global scientific community, nurturing expertise in the field and building infrastructure for both high-end, state-of-the-art as well as undergraduate research in India. Arun Shukla and his team’s work has collectively advanced our understanding of GPCR biology, offering valuable insights for developing drugs targeting these receptors and has been highlighted by India Alliance earlier this year (https://www.indiaalliance.org/news/arun-shukla-profile). They have made significant contributions to the understanding of molecular mechanisms governing GPCR interactions with β-arrestins, shedding light on crucial aspects of receptor activation and signalling. 2023-24 also saw their work appear in highly prestigious journals, some of which are listed below. (Figure 2)

• Maharana J, Sarma P, Yadav MK, Saha S, Singh V, Saha S, Chami M, Banerjee R, Shukla AK. Structural snapshots uncover a key phosphorylation motif in GPCRs driving β-arrestin activation.
  Molecular Cell. 2023 Jun 15;83(12):2091-2107.e7. PMID: 37209686.
• Sarma P, Carino CMC, Seetharama D, Pandey S, Dwivedi-Agnihotri H, Rui X, Cao Y, Kawakami K, Kumari P, Chen YC, Luker KE, Yadav PN, Luker GD, Laporte SA, Chen X, Inoue A, Shukla AK. Molecular insights into intrinsic transducer-coupling bias in the CXCR4-CXCR7 system.
  Nature Communication 2023 Aug 9;14(1):4808. PMCID: PMC10412580.
• Maharana J, Sano FK, Sarma P, Yadav MK, Duan L, Stepniewski TM, Chaturvedi M, Ranjan A, Singh V, Saha S, Mahajan G, Chami M, Shihoya W, Selent J, Chung KY, Banerjee R, Nureki O, Shukla AK. Molecular insights into atypical modes of β-arrestin interaction with seven transmembrane receptors. Science. 2024 Jan 5;383(6678):101-108. PMID: 38175886.

C. R Mahalakshmi, a DBT/WT Senior Fellow at the Indian Institute of Science Education and Research, Bhopal, and a recipient of the DBT S. Ramachandran National Bioscience Award for Career Development in 2023, has been decoding the mysteries surrounding the three vital protein complexes of human mitochondria. Her team has been developing state-of-the-art techniques and novel experimental approaches to understand how TOM, SAM, and VDACs function in their membrane environment. Her work (covered by India Alliance earlier this year https://www.indiaalliance.org/news/decoding-momps) addresses how the dysregulation of these proteins under adverse cellular conditions can trigger extreme disease states, including various cancers, or even lead to neurodegenerative disorders including Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. Her laboratory’s findings have opened exciting avenues to study other membrane proteins on a large scale, while also helping develop therapeutics that suppress premature misfolding and malfunction of VDACs in mitochondrial membranes. Prof Mahalakshmi’s work has now brought the scientific community closer to making therapeutics for neurodegenerative diseases including Parkinson’s and Alzheimer’s disease, a reality. (Figure 3: )

D. Ajit Chande, a DBT/Wellcome Trust Intermediate Fellowis at the Indian Institute of Science Education and Research (IISER) in Bhopal, India and was selected as one of the EMBO Global Investigators 2023 cohort. His laboratory is studying the evolution of retroviruses like HIV-1. Dr Chande’s laboratory was recently highlighted by India Alliance https://www.indiaalliance.org/news/meet-citran. His research focuses on mapping the cellular processes that underlie retrovirus replication at both protein and RNA levels. This knowledge will be used to develop efficient gene delivery vehicles and gene regulatory circuits. The global HIV burden persists, with approximately 39.0 million individuals affected (Global Health Observatory, 2022), highlighting the need for novel therapeutic strategies. Ajit's work unravelling the complexities of molecules within the viral realm is also helping to develop innovative tools like circDR-Seq, enabling the discovery and offering options available to lower the burden of HIV. A notable publication, as below, from his team focused on the potential roles of circular RNAs in HIV-1 infection. (Figure 4: )

• Bhardwaj V, Singh A, Choudhary A, Dalavi R, Ralte L, Chawngthu RL, Senthil Kumar N, Vijay N, Chande A. HIV-1 Vpr induces ciTRAN to prevent transcriptional repression of the provirus.
  Science Advances 2023 Sep 8;9(36):eadh9170. PMID: 37672576; PMCID: PMC10482341.

Figures:

Figure 1: Image showing DBT/WT India Alliance Fellows who have been recognized by prestigious awards in 2023

Figure 2:Graphical abstract of Maharana et al. June 2023. The paper provides important structural insights into the ability of distinct G-Protein Coupled Receptors to activate β-arrestin through a significantly conserved mechanism.

Figure 3:The three gatekeeper proteins of the mitochondrion, namely the TOM complex (protein transporter), SAM complex (protein chaperone), and VDACs (metabolite flux governators) in the outer mitochondrial membrane (OMM).

Figure 4:The circDR-Seq method enriches the circular RNA pool making it easier for direct RNA nanopore sequencing to detect circular RNAs (Left panel). The method was used to identify ciTRAN, a circular RNA that promotes HIV-1 transcription (Right panel).

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