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A 3D model of the lung could change how India tests for TB drugs

Cutting edge research at IISc, Bengaluru, is expected to arm India’s fight against TB as it still carries one of the world’s largest disease burdens.

The innovation could aid faster and more reliable testing of new and drug-resistant TB treatments in India.IISc researchers have developed a 3D lung model that mirrors real human tissue, revealing TB behaviour and drug responses missed by conventional lab systems. (File Photo)

Studying tuberculosis (TB) in the lab has long meant relying on flat cell cultures that look nothing like the human lung. In a breakthrough approach, researchers at the Indian Institute of Science (IISc), Bengaluru, have built a three-dimensional model that better reflects how TB behaves inside the body. Using a soft collagen gel that mimics the texture and structure of lung tissue, the 3D model reveals disease features and drug responses that conventional lab systems often miss.

Cutting edge research is expected to arm India’s fight against TB as it still carries one of the world’s largest burdens (estimated to be around 2.5-3 million cases). The research is funded by India Alliance, a partnership between the Department of Biotechnology and Wellcome Trust, UK.

What’s the efficacy of the new model?

Infected human immune cells were injected into the model. Soon the researchers found that both the human cells and TB bacteria behaved much more like they do in real patients than in flat (2D) lab models. Key TB features such as fat-filled immune cells and clusters of TB bacteria also appeared in this model.

According to Dr Rachit Agarwal, a DBT/Wellcome Trust Intermediate Fellow at IISc, this model could demonstrate the effects of the TB drug Pyrazinamide, something that other lab models usually fail to show. “This new 3D system is a much more realistic way to study TB and test new medicines that could help speed up treatments,” he says.

This 3D hydrogel model is different from existing 2D infection models because it provides mechanical and biochemical cues to host cells and bacteria that are similar to those of the human lung micro environment. It is modular, scalable and can be easily adopted to study drug efficacy and infection biology for extended periods.

What are existing models to test drug efficacy?

At the most basic level, drug testing is performed directly on planktonic bacterial cultures. “Another popular model is to use mammalian cells cultured on two-dimensional plates. These mammalian cells are infected with bacteria and tested with the drugs. However, results from either of these models may not translate effectively into humans, as seen with Pyrazinamide. Alternatively, drug testing is routinely conducted on animal models, such as mice. But with the new FDA Modernisation Act 3.0 (USA) and the New Drugs and Clinical Trials Rules (India), three-dimensional organoids and organ-on-a-chip models are advocated as reliable substitutes for testing safety and efficacy of drugs before human trials,” Dr Agarwal explains.

Is it possible to test and identify drugs that work against DR and XDR bacteria?

Given the ease of making these hydrogels and their similarity to human tissue, it is possible to conduct reliable drug efficacy testing. “While so far, we have not carried out drug resistant bacteria studies in this model, by infecting mammalian cells in our hydrogels with drug-resistant clinical bacterial isolates, it should be possible to test and identify drugs that work against drug-resistant (DR) and XDR (extensively drug-resistant) bacteria,” he says.

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A hotspot for drug-resistant TB, India has been one of the major contributors to the global MDR (multi drug-resistant)/RR-TB (Rifampicin-Resistant TB) in 2024. Rifampicin is a first line broad-spectrum antibiotic.

Dr Agarwal says that researchers are building on this model to further mimic tuberculosis granulomas – tight aggregates of immune cells surrounding the bacteria, a pathological hallmark of TB. “These tight structures in the lung have varying disease outcomes, ranging from bacterial clearance to containment to bacterial outgrowth and can also pose challenges for drug delivery to the core. Such a model could be of immense importance to the field in understanding host-pathogen interactions and drug efficacies,” he adds.

Anuradha Mascarenhas is a Senior Editor at The Indian Express, based in Pune. With a career spanning three decades, she is one of the most respected voices in Indian journalism regarding healthcare, science and environment and research developments. She also takes a keen interest in covering women's issues . Professional Background Education: A gold medalist in Communication and Journalism from Savitribai Phule Pune University and a Master’s degree in Literature. Author: She authored the biography At The Wheel Of Research, which chronicles the life and work of Dr. Soumya Swaminathan, the former Chief Scientist at the WHO. Key Focus: She combines scientific accuracy with storytelling, translating complex medical research into compelling public and human-interest narratives. Awards and Recognition Anuradha has won several awards including the Press Council of India's national award for excellence in journalism under the gender based reporting category in 2019 and the Laadli Media award (gender sensitivity -2024). A recipient of the Lokmat journalism award (gender category-2022), she was also shortlisted for the RedInk awards for excellence in journalism-2021. Her debut book At The Wheel Of Research, an exclusive biography of Dr Soumya Swaminathan the inaugural chief scientist of World Health Organisation was also nominated in the Popular Choice Category of JK Paper AUTHER awards. She has also secured competitive fellowships including the Laadli Media Fellowship (2022), the Survivors Against TB – New Research in TB Media Fellowship (2023) and is part of the prestigious 2025 India Cohort of the WomenLift Health Leadership Journey.” Recent Notable Articles (Late 2025) 1. Cancer & Specialized Medical Care "Tata Memorial finds way to kill drug-resistant cancer cells" (Nov 26, 2025): Reporting on a breakthrough for triple-negative breast cancer, one of the most aggressive forms of the disease. Discipline, diet and purpose; How a 97-year-old professor defies ageing'' (Nov 15, 2025) Report about Prof Gururaj Mutalik, the first Head of Department at Pune's B J Government Medical College who at 97 credits his longevity to healthy habits and a strong sense of purpose. 2. Environmental Health (The "Breathless Pune" Series) Long-term exposure even to 'moderate' air leads to chronic heart, lung, kidney issues" (Nov 26, 2025): Part of an investigative series highlighting that even "safe" pollution levels are damaging to vital organs. "For every 10 µg/m3 increase in PM2.5 level, there was 6-8% jump in medicine sales" (Nov 23, 2025): Using commercial data to prove the direct link between air quality and respiratory illnesses in Pune. 3. Lifestyle & Wellness News "They didn't let cancer, diabetes and heart disease stop them from travelling" (Dec 22, 2025): A collaborative piece featuring survivors who share practical tips for traveling with chronic conditions. At 17, his BP shot up to 200/120 mmHG; Lancet study flags why child and teen hypertension doubled between 2000 and 2020'' (Nov 12,2025)--A report that focusses on 17-year-old-boy's hypertensive crisis and reflects the rising global trend of high blood pressure among children and adolescents. 4. Scientific Recognition & Infrastructure For promoting sci-comm, gender diversity: IUCAA woman prof highlighted in Nature" (Nov 25, 2025): Covering the global recognition of Indian women scientists in gender studies and physics. Pune researchers find a spiral galaxy like the Milky Way from early universe'' (December 3, 2025)- A report on how Indian researchers discovered a massive galaxy that existed when the universe was just 1.5 billion years old , one of the earliest to have been observed so far. Signature Beat: Health, Science & Women in Leadership Anuradha is known for her COVID-19 reportage, where she was one of the first journalists to provide detailed insights into the Covishield and Covaxin trials. She has a dedicated interest in gender diversity in health and science, often profiling women researchers who are breaking the "leaky pipeline" in STEM fields. Her writing style is scrupulous, often featuring interviews with top-tier scientists and health experts from various institutions.   ... Read More

 

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