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Study Reveals Essential Genes That Help Tuberculosis Survive Airborne Transmission

Tuberculosis is a respiratory disease caused by Mycobacterium tuberculosis, a bacterium that predominantly affects the lungs and spreads through droplets released by an infected person

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Image credit: Jomar Junior from Pixabay

Tuberculosis thrives in the lungs, but when the bacteria causing the disease are expelled into the air, they face a much harsher environment with drastic changes in pH and chemistry. Understanding how these bacteria survive this airborne journey is essential for their persistence, yet little is known about the mechanisms that protect them as they move from one host to another.

Now, MIT researchers and their collaborators have identified a family of genes that are crucial for the bacterium’s survival specifically when exposed to the air, likely offering protection during its transmission.

Previously, many of these genes were thought to be nonessential, as they didn’t appear to affect the bacteria’s role in causing disease when introduced into a host. This new study, however, suggests that these genes are vital for transmission rather than proliferation.

“There is a blind spot in our understanding of airborne transmission, especially regarding how a pathogen survives sudden environmental changes as it circulates in the air,” says Lydia Bourouiba, head of the Fluid Dynamics of Disease Transmission Laboratory, associate professor of civil and environmental engineering, mechanical engineering, and core faculty member at MIT’s Institute for Medical Engineering and Science. “Now, through these genes, we have an insight into the tools tuberculosis uses to protect itself.”

The team’s findings, published this week in Proceedings of the National Academy of Sciences, could lead to new tuberculosis therapies that target both infection and transmission prevention.

“If a drug targeted the products of these genes, it could effectively treat an individual and, even before that person is cured, prevent the infection from spreading,” says Carl Nathan, chair of the Department of Microbiology and Immunology and the R.A. Rees Pritchett Professor of Microbiology at Weill Cornell Medicine.

Nathan and Bourouiba co-senior authored the study, which includes MIT collaborators and Bourouiba’s mentees from the Fluids and Health Network: co-lead author postdoc Xiaoyi Hu, postdoc Eric Shen, and students Robin Jahn and Luc Geurts. The research also involved collaborators from Weill Cornell Medicine, the University of California at San Diego, Rockefeller University, Hackensack Meridian Health, and the University of Washington.

Pathogen’s Perspective

Tuberculosis is a respiratory disease caused by Mycobacterium tuberculosis, a bacterium that predominantly affects the lungs and spreads through droplets released by an infected person, typically when they cough or sneeze. Tuberculosis remains the leading cause of death from infection, except during global viral pandemics.

“In the last century, we’ve seen the 1918 influenza pandemic, the 1981 HIV/AIDS epidemic, and the 2019 SARS-CoV-2 pandemic,” notes Nathan. “Each virus has caused significant loss of life, but after they subsided, we were left with the ‘permanent pandemic’ of tuberculosis.”

Much of the research on tuberculosis focuses on its pathophysiology—how the bacteria infect a host—along with diagnostic and treatment methods. For their new study, Nathan and Bourouiba turned their attention to tuberculosis transmission, specifically exploring how the bacteria defend themselves during airborne transmission.

“This is one of the first efforts to study tuberculosis from an airborne perspective, investigating how the organism survives harsh changes in the environment during transmission,” says Bourouiba.

Critical Defense

At MIT, Bourouiba studies fluid dynamics and how droplet behaviors can spread particles and pathogens. She partnered with Nathan, who investigates tuberculosis and the genes that the bacteria rely on throughout their life cycle.

To explore how tuberculosis survives in the air, the team aimed to replicate the conditions the bacterium encounters during transmission. They first worked to develop a fluid with similar viscosity and droplet sizes to those expelled by a person coughing or sneezing. Bourouiba points out that previous research on tuberculosis relied on liquid solutions that are used to grow the bacteria. However, these liquids differ significantly from the fluids tuberculosis patients expel.

Furthermore, the fluid typically sampled from tuberculosis patients, like sputum for diagnostic tests, is thick and sticky, which makes it inefficient at spreading and forming inhalable droplets. “It’s too gooey to break into inhalable droplets,” Bourouiba explains.

Through her research on fluid and droplet physics, the team determined a more accurate viscosity and droplet size distribution for tuberculosis-laden microdroplets in the air. They also analyzed the composition of droplets by studying infected lung tissue samples. They then created a fluid that mimicked the viscosity, surface tension, and droplet size that would be released into the air when a person exhales.

Next, the team deposited different fluid mixtures onto plates as tiny droplets, measuring how they evaporated and what structures they left behind. They discovered that the new fluid shielded the bacteria at the center of the droplet, unlike traditional fluids where bacteria were more exposed to the air. The realistic fluid also retained more water.

The team then infused the droplets with bacteria carrying genes with various knockdowns to see how the absence of specific genes affected bacterial survival during evaporation.

They evaluated over 4,000 tuberculosis genes and identified a family of genes that became crucial in airborne conditions. Many of these genes are involved in repairing damage to oxidized proteins, such as those exposed to air, while others are responsible for breaking down irreparably damaged proteins.

“What we found is a lengthy list of candidate genes, some more prominently involved than others, that could play a critical role in helping tuberculosis survive during transmission,” Nathan says.

While the experiments cannot fully replicate the bacteria’s biophysical transmission (as droplets fly through the air and evaporate), the team mimicked these conditions by placing plates in a dry chamber to accelerate droplet evaporation, similar to what happens in flight.

Going forward, the researchers are developing platforms to study droplets in flight under various conditions. They plan to further investigate the role of the newly identified genes in more realistic experiments, potentially weakening tuberculosis’s airborne defenses.

“The idea of waiting to diagnose and treat someone with tuberculosis is an inefficient way to stop the pandemic,” Nathan says. “Most individuals who exhale tuberculosis haven’t been diagnosed yet, so we need to interrupt its transmission. Understanding the process is key, and now we have some ideas.”

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PUPS – the AI tool that can predict where exactly proteins are in human cells

Dubbed, the Prediction of Unseen Proteins’ Subcellular Localization (or PUPS), the AI tool can account for the effects of protein mutations and cellular stress—key factors in disease progression.

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Credits:Image: Courtesy of the researchers; MIT News

Researchers from MIT, Harvard University, and the Broad Institute have unveiled a groundbreaking artificial intelligence tool that can accurately predict where proteins are located within any human cell, even if both the protein and cell line have never been studied before. The method – Prediction of Unseen Proteins’ Subcellular Localization (or PUPS) – marks a major advancement in biological research and could significantly streamline disease diagnosis and drug discovery.

Protein localization—the precise location of a protein within a cell—is key to understanding its function. Misplaced proteins are known to contribute to diseases like Alzheimer’s, cystic fibrosis, and cancer. However, identifying protein locations manually is expensive and slow, particularly given the vast number of proteins in a single cell.

The new technique leverages a protein language model and a sophisticated computer vision system. It produces a detailed image that highlights where the protein is likely to be located at the single-cell level, offering far more precise insights than many existing models, which average results across all cells of a given type.

“You could do these protein-localization experiments on a computer without having to touch any lab bench, hopefully saving yourself months of effort. While you would still need to verify the prediction, this technique could act like an initial screening of what to test for experimentally,” said Yitong Tseo, a graduate student in MIT’s Computational and Systems Biology program and co-lead author of the study, in a media statement.

Tseo’s co-lead author, Xinyi Zhang, emphasized the model’s ability to generalize: “Most other methods usually require you to have a stain of the protein first, so you’ve already seen it in your training data. Our approach is unique in that it can generalize across proteins and cell lines at the same time,” she said in a media statement.

PUPS was validated through laboratory experiments and shown to outperform baseline AI methods in predicting protein locations with greater accuracy. The tool is also capable of accounting for the effects of protein mutations and cellular stress—key factors in disease progression.

Published in Nature Methods, the research was led by senior authors Fei Chen of Harvard and the Broad Institute, and Caroline Uhler, the Andrew and Erna Viterbi Professor at MIT. Future goals include enabling PUPS to analyze protein interactions and make predictions in live human tissue rather than cultured cells.

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Robot Helps Elderly Sit, Stand, and Stay Safe from Falls

The innovation comes at a time when the United States faces a dramatic demographic shift

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Image credit: MIT News/ Courtesy of the researchers

As America’s population ages faster than ever before, a team of engineers at MIT is turning to robotics to meet the growing eldercare crisis. Their latest invention, the Elderly Bodily Assistance Robot—or E-BAR—aims to provide critical physical support to seniors navigating life at home, potentially reducing the risk of injury and relieving pressure on a strained care system.

The innovation comes at a time when the United States faces a dramatic demographic shift. The nation’s median age has climbed to 38.9, nearly ten years older than in 1980. By 2050, the number of adults over 65 is projected to surge from 58 million to 82 million. As demand for care rises, the country is simultaneously grappling with shortages in care workers, escalating healthcare costs, and evolving family structures that leave many elderly adults without daily support.

“Eldercare is the next great challenge,” said Roberto Bolli, a graduate student in MIT’s Department of Mechanical Engineering and one of E-BAR’s lead designers, in a media statement. “All the demographic trends point to a shortage of caregivers, a surplus of elderly persons, and a strong desire for elderly persons to age in place.”

E-BAR is designed to address exactly that challenge. The mobile robot acts as a robotic support system, following a user from behind and offering both steadying handlebars and rapid intervention in case of a fall. It can support a person’s full weight and includes side airbags that inflate instantly to catch users if they begin to fall—without requiring them to wear any equipment or harnesses.

“Many older adults underestimate the risk of fall and refuse to use physical aids, which are cumbersome, while others overestimate the risk and may not exercise, leading to declining mobility,” said Harry Asada, the Ford Professor of Engineering at MIT, in a media statement. “Our design concept is to provide older adults having balance impairment with robotic handlebars for stabilizing their body. The handlebars go anywhere and provide support anytime, whenever they need.”

The robot consists of a heavy, 220-pound base equipped with omnidirectional wheels, allowing it to maneuver easily through typical home spaces. From its base, articulated bars extend and adjust to assist users in standing or sitting, and the handlebars provide a natural, unrestrictive grip. In testing, E-BAR successfully helped an older adult complete everyday movements such as bending, reaching, and even stepping over the edge of a bathtub.

“Seeing the technology used in real-life scenarios is really exciting,” said Bolli.

The team’s design, which will be presented later this month at the IEEE Conference on Robotics and Automation (ICRA), aims to eliminate the physical constraints and stigmas often associated with eldercare devices. Their approach prioritizes both independence and safety—key values for aging Americans seeking to remain in their homes longer.

While E-BAR currently operates via remote control, the team plans to add autonomous capabilities and streamline the device’s design for home and facility use. The researchers are also exploring ways to integrate fall-prediction algorithms, developed in a parallel project in Asada’s lab, to adapt robotic responses based on a user’s real-time risk level.

“Eldercare conditions can change every few weeks or months,” Asada noted. “We’d like to provide continuous and seamless support as a person’s disability or mobility changes with age.”

As the nation prepares for the realities of an aging population, MIT’s work offers a glimpse into a future where robotics play a central role in eldercare—enhancing both quality of life and personal dignity for millions of older adults.

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Scientist urges need for an Indian-specific blood parameter reference range

In India, standard blood parameter reference ranges aren’t representative of the local population; but based on conclusions derived from population studies in the West.

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Image credit: Pixabay

Prof. Ullas Kolthur-Seetharam, a leading Indian scientist in metabolism and aging, has urged for the re-optimization of standard blood parameter reference ranges to better suit Indian populations, highlighting that current values are based on Western populations and may not account for India-specific factors.

Speaking at the National Technology Day (NTD) 2025 lecture at the Biotechnology Research and Innovation Council-Rajiv Gandhi Centre for Biotechnology (BRIC-R caballoGCB), Kerala, India, Prof. Kolthur-Seetharam emphasized the need for tailored diagnostic benchmarks to improve the accuracy of diagnosing metabolic disorders like diabetes and cardiovascular diseases in India.

“Genetic, dietary, and environmental differences can significantly alter biomarkers,” said Prof. Kolthur-Seetharam, Director of the Centre for DNA Fingerprinting and Diagnostics (BRIC-CDFD), Hyderabad, India. He noted that emerging research reveals how dietary patterns influence health through mitochondrial function and epigenetic regulation, necessitating India-specific reference ranges.

Currently on deputation from the Tata Institute of Fundamental Research (TIFR), Mumbai, Prof. Kolthur-Seetharam has made significant contributions to understanding the interplay of mitochondrial function, epigenetics, and nutrition in shaping health and longevity. He also founded The Advanced Research Unit on Metabolism, Development & Aging (ARUMDA) at TIFR, a pioneering initiative tackling India’s challenges with malnutrition, non-communicable diseases, and aging through interdisciplinary research.

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