Broad Institute of MIT and Harvard

Researchers have found that T cell receptors (TCR) influence T cell activation and differentiation, but it remains unclear how exactly TCR amino acid sequences affect this. Using machine learning and single-cell RNA sequencing, Kaitlyn Lagattuta, Soumya Raychaudhuri, and colleagues analyzed 1 million T cells from seven published datasets, looking at their TCR sequences and transcriptome-wide gene expression profiles. They developed four scoring functions to quantify fates predicted by TCR sequence, and homed in on certain sequence features that promote T cell activation and immunological memory. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

The multi-drug resistant bacterium Pseudomonas aeruginosa is particularly difficult to treat in part because of efflux pumps that make it difficult for small molecules to accumulate within the cell. Bradley Poulsen, Thulasi Warrier, Deb Hung, and colleagues circumvented this problem by targeting the outer membrane. They developed a screening pipeline with mutant P. aeruginosa cells lacking essential proteins either in or associated with the outer membrane. Using this screen, they identified BRD1401, a P. aeruginosa-specific small molecule inhibitor that disrupts interactions between lipopolysaccharides and the membrane protein OprH, increasing membrane fluidity and killing the cell. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

The 12-lead electrocardiogram (ECG) is a low-cost diagnostic tool for various heart conditions. To study its diagnostic potential for other diseases, Sam Friedman, Shaan Khurshid, Steven Lubitz, and colleagues developed a deep learning denoising autoencoder and analyzed associations between ECG encodings and about 1,600 diseases (represented as Phecodes) in three datasets. In npj Digital Medicine, they report associations with more than 1,200 Phecodes, enriched in the circulatory, respiratory, and endocrine/metabolic categories. They also showed how latent space models can generate disease-specific ECG waveforms and could be used for individual disease profiling. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Biological age — a measure of age-related molecular and cellular damage — can be a biomarker of age-related diseases and can differ between organs. Using plasma proteomic, chronological age, and mortality data from more than 50,000 UK Biobank participants, Ludger Goeminne, Vadim Gladyshev, and colleagues have built organ-specific aging models. The models identified protein signatures that indicated accelerated aging and predicted disease in specific organs such as the heart and kidney. The findings, in Cell Metabolism, suggest that accelerated aging in specific organs contributes to chronic age-related diseases in those organs. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

The zinc-finger transcription factor ZNF143 had been thought to be a regulator of looping interactions between promoters and enhancers in the genome, but a new study reveals its true role. In experiments with ZNF143 and known looping regulator CTCF, Domenic Narducci and Anders Sejr Hansen found that ZNF143 has no general looping function in mouse and human cells, functions independently of CTCF, and is not a regulator of chromatin architecture. Instead, it stably binds chromatin and acts as an essential and highly conserved transcription factor regulating important mitochondrial and ribosomal genes. Read more in Molecular Cell. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

📣 Please note: we’ve extended the deadlines for the Autoimmune Disease Machine Learning Challenge: 🔵 Crunch 1: due February 7, 2025 🟠 Crunch 2: due March 21, 2025 🟣 Crunch 3: due April 18, 2025 For more details, visit broad.io/MLC-2024. Good luck with finishing up Crunch 1! Eric and Wendy Schmidt Center, #KlarmanCellObservatory, Broad Institute of MIT and Harvard, Crunch Lab, #Foundry, Laboratory for Innovation Science at Harvard, MIT EECS, MIT Institute for Data, Systems, and Society (IDSS), Mass General Hospital Center for the Study of Inflammatory Bowel Disease

Recent preclinical studies suggest that chronic continuous hypoxia (CCH), or exposure to reduced oxygen levels, could have potential benefits in conditions such as mitochondrial disease, autoimmunity, ischemia, and aging. Yet, hypoxia can also be dangerous. In a Science Translational Medicine review article, Robert Rogers and Vamsi Mootha explore the growing field of research into CCH; outline the barriers to implementing it therapeutically; discuss the insights they hope will come from basic science, high-altitude physiology, clinical medicine, and sports technology; and lay out a path to determine how it might be best evaluated in clinical trials. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

A recent study published in Nature Immunology, co-authored by Ragon Institute faculty member Alex K. Shalek, PhD, provides critical insights into how SARS-CoV-2 variants and vaccination status shape immune responses in the nasal mucosa. This research, which utilized advanced single-cell RNA sequencing (scRNA-seq) approaches, explores how cellular responses in the human nasal cavity differ across viral variants and vaccination statuses, offering new perspectives on COVID-19 immunity. Read more here: https://lnkd.in/gMSYmuEA #RagonInstitute #Immunology #COVID19 #Vaccines

Join us for a Broad Discovery Series talk, "Introducing the immune system, and expanding its cancer-fighting potential," on February 11 at 6 pm ET. The immune system's immense variety of cells and tissues all play specific roles in defending us from pathogens, watching for tumors, keeping the system from inadvertently turning against us, and more. Its T cells in particular are famous for their ability to attack tumors, leading to immunotherapies that have revolutionized cancer treatment. But by focusing on T cells, are we missing other opportunities to combat cancer? Immunologist Lloyd BOD, M.S, PhD will take us on a tour of the immune system, and discuss new insights that may help scientists and doctors leverage its cancer-fighting capabilities more effectively. This talk will take place virtually and in-person at the Broad Institute in Cambridge, MA. Register: https://lnkd.in/eZqqqxsS #BroadInstitute #Science #ScienceTalks #Cancer #CancerResearch Massachusetts General Hospital #BroadDiscoverySeries

Visualizing cells after editing specific genes can help scientists learn new details about the function of those genes. But using microscopy to do this at scale can be challenging, particularly when studying thousands of genes at a time.   Now, a team of Broad and Calico Life Sciences scientists has developed PERISCOPE, an approach that brings the power of microscopy imaging to genome-scale CRISPR screens in a scalable way. The new technique lets researchers study the effects of perturbing over 20,000 genes on hundreds of image-based cellular features. #BroadInstitute #Science #ScienceNews #Research #ScientificResearch #CRISPR