Category: National Institutes of Health (NIH)

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MIT study finds targets for a new tuberculosis vaccine

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A large-scale screen of tuberculosis proteins has revealed several possible antigens that could be developed as a new vaccine for TB, the world’s deadliest infectious disease.

In the new study, a team of MIT biological engineers was able to identify a handful of immunogenic peptides, out of more than 4,000 bacterial proteins, that appear to stimulate a strong response from a type of T cells responsible for orchestrating immune cells’ response to infection.

There is currently only one vaccine for tuberculosis, known as BCG, which is a weakened version of a bacterium that causes TB in cows. This vaccine is widely administered in some parts of the world, but it poorly protects adults against pulmonary TB. Worldwide, tuberculosis kills more than 1 million people every year.

“There’s still a huge TB burden globally that we’d like to make an impact on,” says Bryan Bryson, an associate professor of biological engineering at MIT and a member of the Ragon Institute of Mass General Brigham,

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Particles that enhance mRNA delivery could reduce vaccine dosage and costs

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A new delivery particle developed at MIT could make mRNA vaccines more effective and potentially lower the cost per vaccine dose.

In studies in mice, the researchers showed that an mRNA influenza vaccine delivered with their new lipid nanoparticle could generate the same immune response as mRNA delivered by nanoparticles made with FDA-approved materials, but at around 1/100 the dose.

“One of the challenges with mRNA vaccines is the cost,” says Daniel Anderson, a professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES). “When you think about the cost of making a vaccine that could be distributed widely, it can really add up. Our goal has been to try to make nanoparticles that can give you a safe and effective vaccine response but at a much lower dose.”

While the researchers used their particles to deliver a flu vaccine,

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New nanoparticles stimulate the immune system to attack ovarian tumors

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Cancer immunotherapy, which uses drugs that stimulate the body’s immune cells to attack tumors, is a promising approach to treating many types of cancer. However, it doesn’t work well for some tumors, including ovarian cancer.

To elicit a better response, MIT researchers have designed new nanoparticles that can deliver an immune-stimulating molecule called IL-12 directly to ovarian tumors. When given along with immunotherapy drugs called checkpoint inhibitors, IL-12 helps the immune system launch an attack on cancer cells.

Studying a mouse model of ovarian cancer, the researchers showed that this combination treatment could eliminate metastatic tumors in more than 80 percent of the mice. When the mice were later injected with more cancer cells, to simulate tumor recurrence, their immune cells remembered the tumor proteins and cleared them again.

“What’s really exciting is that we’re able to deliver IL-12 directly in the tumor space.

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Neural activity helps circuit connections mature into optimal signal transmitters

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Nervous system functions, from motion to perception to cognition, depend on the active zones of neural circuit connections, or “synapses,” sending out the right amount of their chemical signals at the right times. By tracking how synaptic active zones form and mature in fruit flies, researchers at The Picower Institute for Learning and Memory at MIT have revealed a fundamental model for how neural activity during development builds properly working connections.

Understanding how that happens is important, not only for advancing fundamental knowledge about how nervous systems develop, but also because many disorders such as epilepsy, autism, or intellectual disability can arise from aberrations of synaptic transmission, says senior author Troy Littleton, the Menicon Professor in The Picower Institute and MIT’s Department of Biology. The new findings, funded in part by a 2021 grant from the National Institutes of Health, provide insights into how active zones develop the ability to send neurotransmitters across synapses to their circuit targets.

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In a surprising discovery, scientists find tiny loops in the genomes of dividing cells

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Before cells can divide, they first need to replicate all of their chromosomes, so that each of the daughter cells can receive a full set of genetic material. Until now, scientists had believed that as division occurs, the genome loses the distinctive 3D internal structure that it typically forms.

Once division is complete, it was thought, the genome gradually regains that complex, globular structure, which plays an essential role in controlling which genes are turned on in a given cell.

However, a new study from MIT shows that in fact, this picture is not fully accurate. Using a higher-resolution genome mapping technique, the research team discovered that small 3D loops connecting regulatory elements and genes persist in the genome during cell division, or mitosis.

“This study really helps to clarify how we should think about mitosis. In the past, mitosis was thought of as a blank slate,

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How the brain splits up vision without you even noticing

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The brain divides vision between its two hemispheres — what’s on your left is processed by your right hemisphere, and vice versa — but your experience with every bike or bird that you see zipping by is seamless. A new study by neuroscientists at The Picower Institute for Learning and Memory at MIT reveals how the brain handles the transition.

“It’s surprising to some people to hear that there’s some independence between the hemispheres, because that doesn’t really correspond to how we perceive reality,” says Earl K. Miller, Picower Professor in the Picower Institute and MIT’s Department of Brain and Cognitive Sciences. “In our consciousness, everything seems to be unified.”

There are advantages to separately processing vision on either side of the brain, including the ability to keep track of more things at once, Miller and other researchers have found,

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How federal research support has helped create life-changing medicines

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Gleevec, a cancer drug first approved for sale in 2001, has dramatically changed the lives of people with chronic myeloid leukemia. This form of cancer was once regarded as very difficult to combat, but survival rates of patients who respond to Gleevec now resemble that of the population at large.

Gleevec is also a medicine developed with the help of federally funded research. That support helped scientists better understand how to create drugs targeting the BCR-ABL oncoprotein, the cancer-causing protein behind chronic myeloid leukemia.

A new study co-authored by MIT researchers quantifies how many such examples of drug development exist. The current administration is proposing a nearly 40 percent budget reduction to the National Institutes of Health (NIH), which sponsors a significant portion of biomedical research. The study finds that over 50 percent of small-molecule drug patents this century cite at least one piece of NIH-backed research that would likely be vulnerable to that potential level of funding change.

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Machine-learning tool gives doctors a more detailed 3D picture of fetal health

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For pregnant women, ultrasounds are an informative (and sometimes necessary) procedure. They typically produce two-dimensional black-and-white scans of fetuses that can reveal key insights, including biological sex, approximate size, and abnormalities like heart issues or cleft lip. If your doctor wants a closer look, they may use magnetic resonance imaging (MRI), which uses magnetic fields to capture images that can be combined to create a 3D view of the fetus.

MRIs aren’t a catch-all, though; the 3D scans are difficult for doctors to interpret well enough to diagnose problems because our visual system is not accustomed to processing 3D volumetric scans (in other words, a wrap-around look that also shows us the inner structures of a subject). Enter machine learning, which could help model a fetus’s development more clearly and accurately from data — although no such algorithm has been able to model their somewhat random movements and various body shapes.

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Alzheimer’s erodes brain cells’ control of gene expression, undermining function, cognition

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Most people recognize Alzheimer’s disease from its devastating symptoms such as memory loss, while new drugs target pathological aspects of disease manifestations, such as plaques of amyloid proteins. Now, a sweeping new open-access study in the Sept. 4 edition of Cell by MIT researchers shows the importance of understanding the disease as a battle over how well brain cells control the expression of their genes. The study paints a high-resolution picture of a desperate struggle to maintain healthy gene expression and gene regulation, where the consequences of failure or success are nothing less than the loss or preservation of cell function and cognition.

The study presents a first-of-its-kind, multimodal atlas of combined gene expression and gene regulation spanning 3.5 million cells from six brain regions, obtained by profiling 384 post-mortem brain samples across 111 donors. The researchers profiled both the “transcriptome,” showing which genes are expressed into RNA,

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A comprehensive cellular-resolution map of brain activity

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The first comprehensive map of mouse brain activity has been unveiled by a large international collaboration of neuroscientists. 

Researchers from the International Brain Laboratory (IBL), including MIT neuroscientist Ila Fiete, published their open-access findings today in two papers in Nature, revealing insights into how decision-making unfolds across the entire brain in mice at single-cell resolution. This brain-wide activity map challenges the traditional hierarchical view of information processing in the brain and shows that decision-making is distributed across many regions in a highly coordinated way.

“This is the first time anyone has produced a full, brain-wide map of the activity of single neurons during decision-making,” explains co-founder of IBL Alexandre Pouget. “The scale is unprecedented as we recorded from over half-a-million neurons across mice in 12 labs, covering 279 brain areas, which together represent 95 percent of the mouse brain volume.

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