Howard Hughes Medical Institute 2009 Annual Report

Tetralogy of Fallot, the most common form of a serious congenital heart defect also known as blue baby syndrome, has always been something of a puzzle. The condition, which causes a newborn’s skin to turn blue from a lack of oxygen in the blood, arises without any hereditary explanation 70 percent of the time; most babies with the condition have parents with normal hearts. Scientists identified small chromosome variations that arose spontaneously in patients. Genes within these regions may harbor mutations that cause these serious heart defects.

Many pathogenic bacteria produce toxins only after they have amassed a large enough group of peers to make their efforts worthwhile. But how do they know their friends are near? It turns out that a form of bacterial chatter called quorum sensing helps rally the troops. New research showed that shutting down the lines of communication between bacteria might be an effective way to prevent microbes from attacking their hosts. The study identified two chemicals that could block quorum sensing at two distinct steps in the signaling pathway, protecting the model organism Caenorhabditis elegans from infection. Medicines that interrupt communication between bacteria could be less likely than traditional antibiotics to spur the development of drug-resistant bacteria.

For those hoping to extend their life by fine-tuning their diet, the available advice can be confusing and even contradictory. Scientists can agree on at least one thing, however: Radically slashing calories is a surefire strategy to increase lifespan—and it appears to work in many different types of animals. In a study that helps explain the phenomenon at the molecular level, HHMI researchers identified two proteins that allow flatworms subsisting on just 60 percent of the calories in a worm’s typical diet to live twice as long as worms allowed as much food as they desired.

In the future, doctors may be able to tailor a dose of radiation therapy based on a patient’s genetic profile. To do that, researchers need to know which genes determine a person’s sensitivity to radiation. After analyzing the activity of more than 10,000 genes, HHMI researchers pinpointed 18 radiation-response genes that influence cells’ reactions to the DNA-damaging rays. The study could help physicians know when it’s possible to reduce radiation dosages—preventing tissue damage and minimizing the risk of secondary cancers—without limiting the therapy’s effectiveness.

Every neuron in the human brain connects with about 1,000 other neurons, but most of those connections are weak; usually a neuron responds only when it gets a simultaneous signal from many others. The authors of a new study were therefore surprised to find that a single neuron has the power to shift large-scale patterns of activity. Experiments with anesthetized rats demonstrated that a single neuron firing at high frequency switched the brain back and forth between very different states of arousal.