On the surface, the movement disorder amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, and the cognitive disorder frontotemporal lobar degeneration (FTLD), which underlies frontotemporal dementia, manifest in very different ways. In addition, they are known to primarily affect very different regions of the brain. However, doctors and scientists have noted several similarities over the years, and a new study appearing in the journal Cell reveals that the diseases have remarkable overlaps at the cellular and molecular levels, revealing potential targets that could yi ..read more

Lyme disease, a bacterial infection transmitted by ticks, affects nearly half a million people in the United States every year. In most cases, antibiotics effectively clear the infection, but for some patients, symptoms linger for months or years. Researchers at MIT and the University of Helsinki have now discovered that human sweat contains a protein that can protect against Lyme disease. They also found that about one-third of the population carries a genetic variant of this protein that is associated with Lyme disease in genome-wide association studies. It’s unknown exactly how the protein ..read more

Tumors can carry mutations in hundreds of different genes, and each of those genes may be mutated in different ways — some mutations simply replace one DNA nucleotide with another, while others insert or delete larger sections of DNA. Until now, there has been no way to quickly and easily screen each of those mutations in their natural setting to see what role they may play in the development, progression, and treatment response of a tumor. Using a variant of CRISPR genome-editing known as prime editing, MIT researchers have now come up with a way to screen those mutations much more easily. Th ..read more

Sequencing all of the RNA in a cell can reveal a great deal of information about that cell’s function and what it is doing at a given point in time. However, the sequencing process destroys the cell, making it difficult to study ongoing changes in gene expression. An alternative approach developed at MIT could enable researchers to track such changes over extended periods of time. The new method, which is based on a noninvasive imaging technique known as Raman spectroscopy, doesn’t harm cells and can be performed repeatedly. Using this technique, the researchers showed that they could monitor ..read more

Every cell in the human body contains the same genetic instructions, encoded in its DNA. However, out of about 30,000 genes, each cell expresses only those genes that it needs to become a nerve cell, immune cell, or any of the other hundreds of cell types in the body. Each cell’s fate is largely determined by chemical modifications to the proteins that decorate its DNA; these modification in turn control which genes get turned on or off. When cells copy their DNA to divide, however, they lose half of these modifications, leaving the question: How do cells maintain the memory of what kind of ce ..read more

While any two human genomes are about 99.9 percent identical, genetic variation in the remaining 0.1 percent plays an important role in shaping human diversity, including a person’s risk for developing certain diseases. Measuring the cumulative effect of these small genetic differences can provide an estimate of an individual’s genetic risk for a particular disease or their likelihood of having a particular trait. However, the majority of models used to generate these “polygenic scores” are based on studies done in people of European descent, and do not accurately gauge the risk for people of ..read more

A diverse set of species, from snails to algae to amoebas, make programmable DNA-cutting enzymes called Fanzors — and a new study from scientists at MIT’s McGovern Institute for Brain Research has identified thousands of them. Fanzors are RNA-guided enzymes that can be programmed to cut DNA at specific sites, much like the bacterial enzymes that power the widely used gene-editing system known as CRISPR. The newly recognized diversity of natural Fanzor enzymes, reported Sept. 27 in the journal Science Advances, gives scientists an extensive set of programmable enzymes that might be adapted into ..read more

A strategy for cellular reprogramming involves using targeted genetic interventions to engineer a cell into a new state. The technique holds great promise in immunotherapy, for instance, where researchers could reprogram a patient’s T-cells so they are more potent cancer killers. Someday, the approach could also help identify life-saving cancer treatments or regenerative therapies that repair disease-ravaged organs. But the human body has about 20,000 genes, and a genetic perturbation could be on a combination of genes or on any of the over 1,000 transcription factors that regulate the genes ..read more

Alzheimer’s disease affects more than 6 million people in the United States, and there are very few FDA-approved treatments that can slow the progression of the disease. In hopes of discovering new targets for potential Alzheimer’s treatments, MIT researchers have performed the broadest analysis yet of the genomic, epigenomic, and transcriptomic changes that occur in every cell type in the brains of Alzheimer’s patients. Using more than 2 million cells from more than 400 postmortem brain samples, the researchers analyzed how gene expression is disrupted as Alzheimer’s progresses. They also tra ..read more

Cancer drugs known as checkpoint blockade inhibitors have proven effective for some cancer patients. These drugs work by taking the brakes off the body’s T cell response, stimulating those immune cells to destroy tumors. Some studies have shown that these drugs work better in patients whose tumors have a very large number of mutated proteins, which scientists believe is because those proteins offer plentiful targets for T cells to attack. However, for at least 50 percent of patients whose tumors show a high mutational burden, checkpoint blockade inhibitors don’t work at all. A new study from M ..read more