With AI, researchers predict the location of virtually any protein within a human cell

with-ai,-researchers-predict-the-location-of-virtually-any-protein-within-a-human-cell

A protein located in the wrong part of a cell can contribute to several diseases, such as Alzheimer’s, cystic fibrosis, and cancer. But there are about 70,000 different proteins and protein variants in a single human cell, and since scientists can typically only test for a handful in one experiment, it is extremely costly and time-consuming to identify proteins’ locations manually.

A new generation of computational techniques seeks to streamline the process using machine-learning models that often leverage datasets containing thousands of proteins and their locations, measured across multiple cell lines. One of the largest such datasets is the Human Protein Atlas, which catalogs the subcellular behavior of over 13,000 proteins in more than 40 cell lines. But as enormous as it is, the Human Protein Atlas has only explored about 0.25 percent of all possible pairings of all proteins and cell lines within the database.

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Study shows vision-language models can’t handle queries with negation words

study-shows-vision-language-models-can’t-handle-queries-with-negation-words

Imagine a radiologist examining a chest X-ray from a new patient. She notices the patient has swelling in the tissue but does not have an enlarged heart. Looking to speed up diagnosis, she might use a vision-language machine-learning model to search for reports from similar patients.

But if the model mistakenly identifies reports with both conditions, the most likely diagnosis could be quite different: If a patient has tissue swelling and an enlarged heart, the condition is very likely to be cardiac related, but with no enlarged heart there could be several underlying causes.

In a new study, MIT researchers have found that vision-language models are extremely likely to make such a mistake in real-world situations because they don’t understand negation — words like “no” and “doesn’t” that specify what is false or absent. 

“Those negation words can have a very significant impact, and if we are just using these models blindly,

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Biologists identify targets for new pancreatic cancer treatments

biologists-identify-targets-for-new-pancreatic-cancer-treatments

Researchers from MIT and Dana-Farber Cancer Institute have discovered that a class of peptides expressed in pancreatic cancer cells could be a promising target for T-cell therapies and other approaches that attack pancreatic tumors.

Known as cryptic peptides, these molecules are produced from sequences in the genome that were not thought to encode proteins. Such peptides can also be found in some healthy cells, but in this study, the researchers identified about 500 that appear to be found only in pancreatic tumors.

The researchers also showed they could generate T cells targeting those peptides. Those T cells were able to attack pancreatic tumor organoids derived from patient cells, and they significantly slowed down tumor growth in a study of mice.

“Pancreas cancer is one of the most challenging cancers to treat. This study identifies an unexpected vulnerability in pancreas cancer cells that we may be able to exploit therapeutically,” says Tyler Jacks,

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New molecular label could lead to simpler, faster tuberculosis tests

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Tuberculosis, the world’s deadliest infectious disease, is estimated to infect around 10 million people each year, and kills more than 1 million annually. Once established in the lungs, the bacteria’s thick cell wall helps it to fight off the host immune system.

Much of that cell wall is made from complex sugar molecules known as glycans, but it’s not well-understood how those glycans help to defend the bacteria. One reason for that is that there hasn’t been an easy way to label them inside cells.

MIT chemists have now overcome that obstacle, demonstrating that they can label a glycan called ManLAM using an organic molecule that reacts with specific sulfur-containing sugars. These sugars are found in only three bacterial species, the most notorious and prevalent of which is Mycobacterium tuberculosis, the microbe that causes TB.

After labeling the glycan, the researchers were able to visualize where it is located within the bacterial cell wall,

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Study of facial bacteria could lead to probiotics that promote healthy skin

study-of-facial-bacteria-could-lead-to-probiotics-that-promote-healthy-skin

The composition of bacterial populations living on our faces plays a significant role in the development of acne and other skin conditions such as eczema. Two species of bacteria predominate in most people, but how they interact with each other, and how those interactions may contribute to disease, has been difficult to study.

MIT researchers have now revealed the dynamics of those interactions in more detail than previously possible, shedding light on when and how new bacterial strains emerge on the skin of the face. Their findings could help guide the development of new treatments for acne and other conditions, and may also help to optimize the timing of such treatments.

The researchers found that many new strains of Cutibacterium acnes, a species believed to contribute to the development of acne, are acquired during the early teenage years. But after that, the makeup of these populations becomes very stable and doesn’t change much even when exposed to new strains.

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Equipping living cells with logic gates to fight cancer

equipping-living-cells-with-logic-gates-to-fight-cancer

One of the most exciting developments in cancer treatment is a wave of new cell therapies that train a patient’s immune system to attack cancer cells. Such therapies have saved the lives of patients with certain aggressive cancers and few other options. Most of these therapies work by teaching immune cells to recognize and attack specific proteins on the surface of cancer cells.

Unfortunately, most proteins found on cancer cells aren’t unique to tumors. They’re also often present on healthy cells, making it difficult to target cancer aggressively without triggering dangerous attacks on other tissue. The problem has limited the application of cell therapies to a small subset of cancers.

Now Senti Bio is working to create smarter cell therapies using synthetic biology. The company, which was founded by former MIT faculty member and current MIT Research Associate Tim Lu ’03, MEng ’03, PhD ’08 and Professor James Collins,

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