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as a science writer for the Broad Institute of MIT and Harvard

Broad Institute •

New technique expands cells to sequence DNA and capture fine structural details

Broad Institute researchers have developed a technology that provides new insight into how disruptions in the nucleus of the cell can impact health and disease.
The approach, called expansion in situ genome sequencing, allows scientists to sequence DNA and map its location relative to proteins within cell nuclei. The method uses a gel to expand cells while keeping them intact, enabling both sequencing and high-resolution imaging within the same cells. The research team applied their technique to...
Broad Institute •

Making antibiotics more potent against drug-resistant bacteria

Researchers have created a pipeline for discovering unique combinations of molecules that increase the effectiveness of antibiotics against drug-resistant bacteria. The team, led by scientists at the Broad Institute and the Tufts University School of Medicine, used a microfluidic approach to screen more than 1 million combinations of antibiotics, small molecules, and bacteria. They identified a small molecule that boosts the power of the antibiotic rifampin in certain bacteria by weakening their...
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Gene editing disrupts Huntington’s mutation in mice

Broad Institute researchers have developed a way to edit the genetic sequences at the root of Huntington’s disease and Friedreich’s ataxia.
The conditions are two of more than 40 severe neurological disorders caused by three-letter stretches of DNA that repeat consecutively. If longer than a certain threshold length, these sequences grow in length uncontrollably and lead to brain cell death in Huntington’s disease, and the breakdown of nerve fibers in Friedreich’s ataxia. There are no treatments...
Broad Institute •

New study aims to uncover the genetics of anorexia and other eating disorders

A new direct-to-participant effort now underway is giving people the opportunity to participate in the largest and most diverse genetic study of anorexia nervosa and other eating disorders to date. Researchers at the Broad Institute Ben Neale and Mark Daly are co-leading the study, which allows people across the US to sign up to have their DNA analyzed as part of this effort. 
The team aims to collect and study DNA from 6,000 newly recruited people that will contribute to a larger study goal of...
Broad Institute •

Evolved gene editor inserts entire genes in human cells

Researchers from the Broad Institute and Columbia University have developed a way to insert entire healthy genes into human cells efficiently enough for potential therapeutic applications. It lays a foundation for gene-editing therapies for patients with different mutations that cause a genetic disease.
The approach uses laboratory-evolved versions of enzymes called CRISPR-associated transposases, or CASTs, which move large stretches of DNA in bacterial genomes but have so far shown minimal acti...
Broad Institute •

#WhyIScience Q&A: A systems biologist uses AI to understand how the genome controls cell fate

Growing up in the Sichuan province in China, Bo Xia was curious about the nature he saw around him: the creeks that ran through his hometown and its many animals and insects. In school, he loved imagining how molecules made up materials and whole organisms. He read about graphene in a textbook and was intrigued by how the material’s structure — a single layer of carbon atoms patterned like a honeycomb — granted it special electronic properties.
As an undergraduate, Xia studied biology and chemis...
Broad Institute •

Scientists have developed a way to scale up spatial genomics and lower costs

Spatial transcriptomics technologies opened the door for new kinds of biological measurements, allowing scientists to generate detailed maps of where genes are expressed in tissue. But most methods rely on expensive and time-intensive imaging that requires specialized equipment.
A new method developed by researchers at the Broad Institute promises to make spatial transcriptomics easier for scientists to use. The approach eliminates the need for imaging and instead uses computational methods to r...
Broad Institute •

Why brain cancer is often resistant to immunotherapy

Immunotherapy has revolutionized the treatment of many cancers, but brain tumors such as gliomas remain particularly difficult to treat, in part because they potently suppress immune responses.
New findings from researchers at the Broad Institute of MIT and Harvard and the Dana-Farber Cancer Institute (DFCI) could help make immunotherapies for brain cancer more effective.
The team analyzed almost 200,000 individual immune cells called myeloid cells from tumor samples from patients with glioma, t...
Broad Institute •

Mutations in two gene pairs point to a promising drug target in 5 percent of adult cancers

Scientists from the Cancer Dependency Map (DepMap) at the Broad Institute of MIT and Harvard and Columbia University have discovered that about 5 percent of adult cancers rely heavily on a gene called PELO to survive and that disabling the gene kills those cancer cells. These cancers have mutations in one of two genes, FOCAD or TTC37.
The finding, described today in Nature, is a new synthetic lethality — a pair of genetic changes that together kill cancer cells. The researchers say that PELO is...
Broad Institute •

A genome-wide atlas of cell morphology reveals gene functions

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, researchers at the Broad Institute of MIT and Harvard, along with collaborators at Calico Life Sciences, have developed an approach that brings the power of microscopy imaging to genome-scale CRISPR screens in a scalable way. 
PERISCOPE — which stands for p...
Broad Institute •

Study finds surprising way that genetic mutation causes Huntington’s disease, transforming understanding of the disorder

Scientists at the Broad Institute of MIT and Harvard, Harvard Medical School, and McLean Hospital have discovered a surprising mechanism by which the inherited genetic mutation known to cause Huntington’s disease leads to the death of brain cells. The findings change the understanding of the fatal neurodegenerative disorder and suggest potential ways to delay or even prevent it.
For 30 years, researchers have known that Huntington’s is caused by an inherited mutation in the Huntingtin (HTT) gene...
Broad Institute •

Gene editing extends lifespan in mouse model of prion disease

Researchers at the Broad Institute of MIT and Harvard have developed a gene-editing treatment for prion disease that extends lifespan by about 50 percent in a mouse model of the fatal neurodegenerative condition. The treatment, which uses base editing to make a single-letter change in DNA, reduced levels of the disease-causing prion protein in the brain by as much as 60 percent. 
There is currently no cure for prion disease, and the new approach could be an important step towards treatments that...
Broad Institute •

Scientists engineer CRISPR enzymes that evade the immune system

The core components of CRISPR-based genome-editing therapies are bacterial proteins called nucleases that can stimulate unwanted immune responses in people, increasing the chances of side effects and making these therapies potentially less effective. 
Researchers at the Broad Institute of MIT and Harvard and Cyrus Biotechnology have now engineered two CRISPR nucleases, Cas9 and Cas12, to mask them from the immune system. The team identified protein sequences on each nuclease that trigger the imm...
Broad Institute •

A clinical genomicist harnesses team-based science to help rare-disease patients

In the two decades that Heidi Rehm has been a clinical genomicist, she’s accumulated a lot of stories. There’s a patient whose shortness of breath and thickened heart wall suggested a cardiac condition but genetic testing revealed a completely different diagnosis. There’s a newborn whose genomic testing revealed a mutation in BRCA2, a gene commonly linked to breast cancer, prompting family testing and a preventative mastectomy by his mother. And then there are the stories that Rehm especially li...
Broad Institute •

Scientists find a region of the mouse gut tightly regulated by the immune system

The intestine maintains a delicate balance in the body, absorbing nutrients and water while maintaining a healthy relationship with the gut microbiome, but this equilibrium is disrupted in parts of the intestine in conditions such as celiac disease, ulcerative colitis, and Crohn’s disease. Scientists don’t fully understand how different regions of the organ resist or adapt to changes in the environment and how that is disrupted in disease.
Now, researchers at the Broad Institute of MIT and Harva...
Broad Institute •

Q&A: How Terra became a backbone of public health pathogen surveillance

DP: Before Terra, only a handful of state public health labs were analyzing their own genomic data. Most didn't really have a way to do large-scale genomic analysis well. Many relied on the CDC, a neighboring state lab, or an academic partner to assist or perform analyses for them — except for the handful of well-resourced state labs that could hire the right people and build out the right infrastructure, and knew how to use it well. But most state and local public health labs in the US didn’t h...
Broad Institute •

Scientists identify a unique combination of bacterial strains that could treat antibiotic-resistant gut infections

Antibiotic-resistant bacterial infections often occur in patients with chronic inflammatory intestinal conditions, such as inflammatory bowel disease, and in patients who have taken antibiotics for a long time. Gram-negative bacteria such as Enterobacteriaceae are a common cause of these infections and have few treatment options. Fecal microbiota transplants have shown promise to curb some of these infections, but their composition varies between batches and they aren’t always successful. 
Resea...
Broad Institute •

#WhyIScience Q&A: A systems biologist develops computational tools to bring scale to cell experiments

At first, Yue Qin thought she wanted to become a doctor. She’d always been interested in disease — why people got sick, why some illnesses could send you to a hospital while others could be treated at home. As she grew older, however, she realized she was more interested in learning about the roots of disease and the genes that caused them. 
Growing up in Ningbo, a city in eastern China, Qin was strongly influenced by societal expectations that girls were better suited for language arts than mat...
Broad Institute •

Machine learning approach helps researchers design better gene-delivery vehicles for gene therapy

Gene therapy could potentially cure genetic diseases but it remains a challenge to package and deliver new genes to specific cells safely and effectively. Existing methods of engineering one of the most commonly used gene-delivery vehicles, adeno-associated viruses (AAV), are often slow and inefficient. 
Now, researchers at the Broad Institute of MIT and Harvard have developed a machine-learning approach that promises to speed up AAV engineering for gene therapy. The tool helps researchers engin...
Broad Institute •

Q&A: How a stem cell bank is helping scientists understand psychiatric disorders

When Ralda Nehme, a cell biologist and neuroscientist, first started her lab at the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard in 2018, she realized a gap in the field. She was adept at growing stem cells in the lab, converting them into neurons, and using those cells to study the effects of genetic mutations linked to schizophrenia. But she soon realized that to truly capture the complexity of human disease, she would need to study a large number of cells...
Broad Institute •

Prime editing efficiently corrects cystic fibrosis mutation in human lung cells

Cystic fibrosis is one of the most common genetic disorders, causing thick mucus build-up in the lungs and other parts of the body, breathing problems, and infection. A three-drug cocktail known as Trikafta has greatly improved patient quality of life since its development in 2019, but can cause cataracts and liver damage and must be taken daily at a cost of about $300,000 per year.
Now, researchers at the Broad Institute of MIT and Harvard and the University of Iowa have developed a gene-editin...
Broad Institute •

Simple test for flu could improve diagnosis and surveillance

Fewer than one percent of people who get the flu every year get tested in part because most tests require trained personnel and expensive equipment. Now researchers have developed a low-cost paper strip test that could allow more patients to find out which type of flu they have and get the right treatment. 
The test, developed by a team from the Broad Institute of MIT and Harvard and Princeton University, and supported by the US Centers for Disease Control and Prevention, uses CRISPR to distingu...
Broad Institute •

Some CRISPR screens may be missing cancer drug targets

CRISPR/Cas9 gene editing has made possible a multitude of biomedical experiments including studies that systematically turn off genes in cancer cells to look for ones that the cancer cells heavily depend on to survive and grow. These genes, or “cancer dependencies,” are often promising drug targets. But new research shows that many of these CRISPR screening experiments rely on components, called CRISPR/Cas9 guides, that do not perform equally well in cells from people of all ancestries, which ca...
Broad Institute •

Improved prime editing system makes gene-sized edits in human cells at therapeutic levels

Scientists at the Broad Institute of MIT and Harvard have improved a gene-editing technology that is now capable of inserting or substituting entire genes in the genome in human cells efficiently enough to be potentially useful for therapeutic applications.
The advance, from the lab of Broad core institute member David Liu, could one day help researchers develop a single gene therapy for diseases such as cystic fibrosis that are caused by one of hundreds or thousands of different mutations in a...
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