A new discovery about the spatial orientation and physical interactions of our genes provides a promising step forward in our ability to design custom antibodies. This, in turn, could revolutionize the fields of vaccine development and infection control.
Recent years of research by Alt and others in the field of molecular biology have revealed that it’s not just our genes themselves that determine health and disease states. It’s also the three-dimensional arrangement of our genes that plays a role in keeping genetic harmony. Failure of these structures may trigger genetic mutations or genome rearrangements leading to catastrophe.
The importance of genetic loops
Crammed inside the nucleus, chromatin, the chains of DNA and proteins that make up our chromosomes, is arranged in extensive loop arrangements. These loop configurations physically confine segments of genes that ought to work together in a close proximity to one another, increasingly their ability to work in tandem.
“All the genes contained inside one loop have a greater than random chance of coming together,” says Suvi Jain, PhD, a postdoctoral researcher in Alt’s lab and a co-first author on the study.
Meanwhile, genes that ought to stay apart remain blocked from reaching each other, held physically apart inside our chromosomes by the loop structures of our chromatin.
But while many chromatin loops are hardwired into certain formations throughout all our cells, it turns out that some types of cells, such as certain immune cells, are more prone to re-arrangement of these loops. …
For decades, cardiac researcher James McCully, PhD, has been spellbound by the idea of using mitochondria, the “batteries” of the body’s cells, as a therapy to boost heart function. Finally, a clinical trial at Boston Children’s Hospital is bringing his vision — a therapy called mitochondrial transplantation — to life.
Mitochondria, small structures inside all of our cells, synthesize the essential energy that our cells need to function. In the field of cardiac surgery, a well-known condition called ischemia often damages mitochondria and its mitochondrial DNA inside the heart’s muscle cells, causing the heart to weaken and pump blood less efficiently. Ischemia, a condition of reduced or restricted blood flow, can be caused by congenital heart defects, coronary artery disease and cardiac arrest.
For the smallest and most vulnerable patients who are born with severe heart defects, a heart-lung bypass machine called extracorporeal membrane oxygenation (ECMO) can help restore blood flow and oxygenation to the heart. But even after blood flow has returned, the mitochondria and their DNA remain damaged.
“In the very young and the very old, especially, their hearts are not able to bounce back,” says McCully.
Ischemia can be fatal for the tiniest patients
After cardiac arrest, for instance, a child’s mortality rate jumps to above 40 percent because of ischemia’s effects on mitochondria. If a child’s heart is too weak to function without the support of ECMO, his or her risk of dying increases each additional day spent connected to the machine.
But what if healthy mitochondria could come to the rescue and replace the damaged ones? …
First in a two-part series on transplant tolerance.
Although organ transplant recipients take drugs to suppress the inflammatory immune response, almost all eventually lose their transplant. A new approach, perhaps added to standard immunosuppressant treatment, could greatly enhance people’s long-term transplant tolerance, report researchers at Boston Children’s Hospital.
The approach, which has only been tested in mice as of yet, works by maintaining a population of T cells that naturally temper immune responses. It does so by turning on a gene called DEPTOR, which itself acts as a genetic regulator. In a study published July 3 in the American Journal of Transplantation, boosting DEPTOR in T cells enabled heart transplants to survive in mice much longer than usual. …
Tissue expanders — small balloons that can be filled with saline solution or other fluids to grow skin — have long been used in plastic surgery, most commonly breast reconstruction. They’re based on the simple idea that the surrounding skin will stretch as the device expands over time. That extra skin can then help repair injuries or congenital anomalies or accommodate implants.
Midaortic syndrome occurs when the middle section of the aorta is narrowed and typically affects children and young adults. It can cause severe hypertension and can be life-threatening if left untreated. The surgical approach to this condition would be to replace the damaged portion of the aorta with nearby healthy blood vessels. However, this usually isn’t possible because these vessels tend to be too short to adequately fill in. …
Precision medicine is often equated with high-tech, exquisitely targeted, million-dollar drug treatments. But at Precision Medicine 2018, hosted by Harvard Medical School’s Department of Biomedical Informatics (DBMI) this week, many of the speakers and panelists were more concerned about improving health for everyone and making better use of what we already have: data.
“We’re not going to make major changes in 21st century medicine without embracing data-driven approaches,” said HMS dean George Q. Daley in his opening remarks. …
Kaylee Goodwin, 29, has struggled her whole life to control her blood levels of “phe” — the amino acid known as phenylalanine. “I was told that if my levels were controlled, I would be able to think more clearly and feel better overall,” she says.
Goodwin was born with phenylketonuria (PKU), a genetic metabolic disorder affecting roughly 1 in 16,000 newborns. Her body can’t break down phe because of a genetic mutation disabling the necessary enzyme, phenylalanine hydroxylase (PAH).
If left untreated, phe accumulates in the brain, causing intellectual disability and seizures. But starting in the early 1960s, newborn screening programs have been able to test for PKU. Goodwin tested positive and was prescribed a special phe-free diet by Harvey Levy, MD, at Boston Children’s Hospital.
Through the diet, Goodwin has dodged serious brain damage and was able to attend college and start a career as a dancer and actress. But because phe is in nearly all naturally occurring proteins, she couldn’t eat meat, eggs, dairy products, legumes, most grains and many fruits and vegetables. Instead, she had to consume a foul-tasting amino acid formula.
“I spent my entire life carrying special foods and medical formula around with me, and weighing and measuring foods,” she says. …
The hope to improve people’s lives is what drives many members of industry and academia to bring new products and therapies to market. At the BIO International Convention last week in Boston, there was lots of discussion about how translational science intersects with patients’ needs and why the best therapeutic developmental pipelines are consistently putting patients first.
“Our mission is to de-risk entry of new therapies in the ASD drug discovery and development space,” said Sahin, who is also a professor of neurology at Harvard Medical School.
One big challenge, says Sahin, is knowing how well — or how poorly — autism therapies are actually affecting people with ASD. Externally, ASD is recognized by its core symptoms of repetitive behaviors and social deficits. …
This is part I of a two-part blog series recapping the 2018 BIO International Convention.
At the 2018 BIO International Convention last week, it was clear what’s provoking scientific minds in industry and academia — or at least those of the Guinness-world-record-making 16,000 people in attendance. Artificial intelligence, machine learning and their implications for tailor-made medicine bubbled up across all BIO’s educational tracks and a majority of discussions about the future state of biotechnology. Panelists from Boston Children’s Hospital also contributed their insights to what’s brewing at the intersection of these burgeoning fields.
Isaac Kohane, MD, PhD, former chair of Boston Children’s Computational Health and Informatics Program, spoke on a panel about how large-scale patient data — if properly harnessed and analyzed for health and disease trends — is a virtual goldmine for precision medicine insights. Patterns gleaned from population health data or electronic health records, for example, could help identify which subgroups of patients who might respond better to specific therapies.
According to Kohane, who is currently the Marion J. Nelson Professor of Biomedical Informatics and Pediatrics at Harvard Medical School (HMS), we will soon be leveraging artificial intelligence to go through patient records and determine exactly what doctors were thinking when they saw patients.
“We’ve seen again and again that data abstraction by artificial intelligence is better than abstraction by human analysts when performed at the scale of millions of clinical notes across thousands of patients,” said Kohane.
And based on what we heard at BIO, artificial intelligence will revolutionize more than patient data mining. It will also transform the way we design precision therapeutics — and even vaccines — from the ground up. …
Since the late 1970s, biologists have known that blood develops in a specific body location. But they’ve wondered why different creatures house their blood stem cells in different places. In humans and other mammals, they’re in the bone. In fish, they’re in the kidney. Why?
Over-prescribing has long been thought to increase antibiotic resistance in bacteria. But could much bigger environmental pressures be at play?
While studying the role of climate on the distribution of antibiotic resistance across the geography of the U.S., a multidisciplinary team of epidemiologists from Boston Children’s Hospital found that higher local temperatures and population densities correlate with higher antibiotic resistance in common bacterial strains. Their findings were published today in Nature Climate Change.
“The effects of climate are increasingly being recognized in a variety of infectious diseases, but so far as we know this is the first time it has been implicated in the distribution of antibiotic resistance over geographies,” says the study’s lead author, Derek MacFadden, MD, an infectious disease specialist and research fellow at Boston Children’s Hospital. “We also found a signal that the associations between antibiotic resistance and temperature could be increasing over time.”
During their study, the team assembled a large database of U.S. antibiotic resistance in E. coli, K. pneumoniae and S. aureus, pulling from hospital, laboratory and disease surveillance data documented between 2013 and 2015. Altogether, their database comprised more than 1.6 million bacterial specimens from 602 unique records across 223 facilities and 41 states. …