Cells throughout the human body are constantly being damaged as a part of natural life, normal cellular processes, UV and chemical exposure and environmental factors — resulting in what are called DNA double-strand breaks. Thankfully, to prevent the accumulation of DNA damage that could eventually lead to cell dysfunction, cancer or death, the healthy human body has developed ways of locating and repairing the damage.
Unfortunately, these DNA repair mechanisms themselves are not impervious to genetic errors. Genetic mutations that disrupt DNA repair can contribute to devastating disease.
Across the early-stage progenitor cells that give rise to the human brain’s 80 billion neuronal cells, genomic alterations impacting DNA repair processes have been linked to neuropsychiatric disorders and the childhood brain cancer medulloblastoma. But until now, it was not known exactly which disruptions in DNA repair were involved.
The human body’s innate immune system employs a variety of “sensors” for identifying foreign invaders such as viruses. One such viral sensor is a receptor called MDA5, found in every cell of the body.
Inside each cell, MDA5 constantly scans genetic material, checking if it’s native to the body or not. As soon as MDA5 identifies the genetic signature of a viral invader, it trips a system-wide alarm, triggering a cascade of immune activity to neutralize the threat.
But if a genetic mutation to MDA5 causes it to confuse some of the body’s own genetic material for being foreign, “false alarms” can lead to unchecked inflammation and disease. Scientists from Boston Children’s Hospital have discovered a new link between MDA5’s ability to discriminate between “self” and “non-self” genetic material — called RNA duplexes — and a spectrum of autoimmune disorders. …
To fight HIV, the development of immunization strategies must keep up with how quickly the virus modifies itself. Now, Boston Children’s Hospital researchers are developing models to test HIV vaccines on a faster and broader scale than ever before with the support of the Bill & Melinda Gates Foundation.
The researchers are racing against HIV’s sophisticated attack on the human immune system. HIV, the human immunodeficiency virus, mutates much faster than other pathogens. Within each infected patient, one virus can multiply by the billions. …
Immune cells called “killer cells” target bacteria invading the body’s cells, but how do they do this so effectively? Bacteria can quickly evolve resistance against antibiotics, yet it seems they have not so readily been able to evade killer cells. This has caused researchers to become interested in finding out the exact mechanism that killer cells use to destroy bacterial invaders.
Although one way that killer cells can trigger bacterial death is by inflicting oxidative damage, it has not yet been at all understood how killer cells destroy bacteria in environments without oxygen.
Now, for the first time, researchers have caught killer cells red-handed in the act of microbial murder …
WATCH: DNA nanoswitches change shape in the presence of biomarkers. The shape change is revealed in a process called gel electrophoresis. Credit: Wyss Institute at Harvard University
“Nanoswitches” — engineered, shape-changing strands of DNA — could shake up the way we monitor our health, according to new research. Faster, easier, cheaper and more sensitive tests based on these tools — used in the lab or at point of care — could indicate the presence of disease, infection and even genetic variabilities as subtle as a single-gene mutation.
“One critical application in both basic research and clinical practice is the detection of biomarkers in our bodies, which convey vital information about our current health,” says lead researcher Wesley Wong, PhD, of Boston Children’s Hospital Program in Cellular and Molecular Medicine (PCMM). “However, current methods tend to be either cheap and easy or highly sensitive, but generally not both.”
Once they detect an invader, inflammasomes send out signals that trigger infected cells to die using an inflammatory death pathway called pyroptosis. They also call for backup from the adaptive immune system, in the form of inflammation. (Image: Wu laboratory/Liman Zhang)
Of the various ways for a cell to die — necrosis, autophagy, etc. — apoptosis is probably the most orderly and contained. Also called programmed cell death (or, colloquially, “cellular suicide”), apoptosis is an effective way for diseased or damaged cells to remove themselves from a population before they can cause problems such as tumor formation.
Conventional wisdom holds that apoptosis is exclusive to multicellular organisms. Lieberman disagrees. She thinks that microbial cells — such as those of bacteria and parasites — can die in apoptotic fashion as well. In a recent Nature Medicine paper, she and her team make the case for the existence of what they’ve dubbed “microptosis.” And they think it could be harnessed to treat parasitic and other infections. …
With SCNT, researchers take an egg cell and replace its nucleus with that of an adult cell (such as a skin cell) from another individual. The donated nucleus basically reboots an embryonic state, creating a clone of the original cell.
It’s a hot topic in both agriculture and regenerative medicine. SCNT-generated cells can be used to clone an animal (remember Dolly the sheep?) or produce embryonic stem (ES) cell lines for research. But it’s an inefficient process, producing very few animal clones or ES lines for the effort and material it takes.
Zhang’s team reported last year that they could boost SCNT’s efficiency significantly by removing an epigenetic roadblock that kept embryonic genes in the donated nucleus from activating in cloned cells. Now, in a new paper in Cell Stem Cell, Zhang and his collaborators report that they’ve extended their work to improve the efficiency of SCNT in human cells.
Self-discovery is a theme that unites Sun Hur’s life and work. Growing up with a passion for physics, Hur pursued a scientific career in chemistry before launching her own research group in biology. Today, Hur, an investigator in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine (PCMM), uses her considerable intellectual gifts to uncover how the immune system distinguishes self from non-self.
In the video above, produced by the Vilcek Foundation (which honors and supports foreign-born scientists and artists who have made outstanding contributions to society in the United States), Hur talks about her personal and scientific journey since coming to the U.S. from her native South Korea in 2000. Overcoming cultural and language barriers, she has turned her childhood fascination with order and chaos toward exploring how the innate immune system recognizes invaders, in particular disease-causing viruses that generate a double-stranded RNA during replication.
Millions of people worldwide suffer from co-infection with tuberculosis (TB) and HIV. While prompt antibiotic and antiretroviral treatment can be a recipe for survival, over the years, physicians have noticed something: two or three weeks after starting antiretrovirals, about 30 percent of co-infected patients get worse.
The reason: immune reconstitution inflammatory syndrome, or IRIS. Doctors think it represents a kind of immune rebound. As the antiretrovirals start to work, and the patient’s immune system begins to recover from HIV, it notices TB’s presence and overreacts.
“It’s as though the immune system was blanketed and then unleashed,” says Luke Jasenosky, PhD, a postdoctoral fellow with Anne Goldfeld, MD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine. “It then says, ‘I can start to see things again, and there are a lot of bacteria in here.'”
Though potentially severe, even fatal, IRIS may actually be a good sign: there is evidence that patients who develop it tend to fare better in the long run. But why does it arise only in some patients? …