howard hughes medical institute

Researcher ID new target for anti-HIV drugs

Researchers say they have discovered a new target on the HIV molecule that could potentially lead to a new class of anti-viral drugs to fight the virus that causes AIDS. “The greatest challenge in treating HIV today is drug resistance brought on when the virus mutates and renders existing drugs ineffective at stopping viral replication,” said a lead researcher. “Our research has led to the identification of a new class of compounds that inhibit a novel target in HIV. These compounds disrupt the assembly of the HIV-1 capsid protein, which is a vital step in changing immature, non-infectious HIV into its mature, infectious form.”

Deceptive Strategy Shields HIV from Destruction

Researchers have discovered one way in which the human immunodeficiency virus (HIV) wins its cat-and-mouse game with the body’s immune system. The study, published in the March 20, 2003, issue of the journal Nature, shows that HIV-1, a common strain of the virus that causes AIDS, uses a strategy not seen before in other viruses to escape attack by antibodies, one of the immune system’s prime weapons against invading viruses and bacteria.

Researchers Identify Signals that Cause Hair Follicles to Sprout

The delicate interplay of two chemical signals coaxes stem cells into becoming hair follicles, according to new research by scientists at the Howard Hughes Medical Institute at The Rockefeller University. The research has implications for understanding hair growth and hair-follicle development, and it may also help explain how diverse structures, such as teeth and lungs, are formed or how some forms of skin cancer develop.

Gene Mutation Exacerbates Eye Defect in Inherited Glaucoma

While studying mice with a mutant gene whose counterpart causes inherited glaucoma in humans, researchers have discovered a second gene mutation that worsens the structural eye defect that causes this type of glaucoma. The newly discovered gene mutation affects production of L-DOPA. The researchers suggest that it might be feasible to prevent glaucoma by administering L-DOPA, which is used in treating Parkinson’s disease.

Pheromones Create a 'Chemical Image' in the Brain

For the first time, researchers have eavesdropped on the brains of mice as they go about the normal behaviors of detecting the subtle chemical signals called pheromones from other animals. The researchers have discovered that the animals’ pheromone-processing machinery in the brain forms, in essence, a specific “pheromonal image” of another animal. Such an “image” of another animal’s sex, identity, social standing and female reproductive status governs a range of mating, fighting, maternal-infant bonding and other behaviors. The scientists said that the specificity they discovered in the neurons that process pheromonal signals is akin to the “face neurons” in the visual areas of primate brains that are specifically triggered by facial features of other animals.

Taste Receptor Cells Share Common Pathway

Although sweet, bitter and umami (monosodium glutamate) tastes are different, researchers are finding that information about each of these tastes is transmitted from the various taste receptors via a common intracellular signaling pathway. The identification of a common pathway runs counter to widespread belief among some researchers in the taste field who have long held the view that the different tastes require distinct machinery within the cell to transduce their signals to the brain, which is responsible for processing taste perceptions.

Mutation Causes Specific Arrhythmia and Sudden Cardiac Death

An international team of researchers has demonstrated a genetic basis for a fatal form of inherited cardiac arrhythmia that usually strikes young, seemingly healthy people. Basing their research on a French family with a form (Type 4) of inherited Long QT Syndrome (LQTS) and experiments in mice, the researchers found the mutation in a specific gene encoding ankyrin-B, a protein within heart muscle cells. Their discovery identifies what appears to be a novel mechanism for cardiac arrhythmia.

Protein Linked to Movement Disorders

Using a tiny worm to model a severe childhood movement disorder, researchers have discovered the role of a protein that may have implications for a number of neurological syndromes such as Parkinson’s and Huntington’s diseases. The scientists found that a mutated gene associated with early onset dystonia, a severe hereditary movement disorder, normally helps manage protein folding.

Mechanism to overcome Gleevec resistance demonstrated

Amid the glowing results for chronic myelogenous leukemia (CML) patients using Gleevec the past three years, the one reality check has been that a majority of the patients with advanced disease eventually relapse and die of the leukemia. An article to be published in the Dec. 15 issue of the journal Cancer Research shows that, in the lab, the molecular mutations that produce a resistance to Gleevec can be overcome. Brian Druker, M.D., Howard Hughes Medical Institute Investigator and JELD-WEN Chair of Leukemia Research at the Oregon Health & Science University Cancer Institute, and colleagues report that a compound called PD180970 successfully stopped the activity of several mutations found in patients who developed a resistance to Gleevec.

Zebrafish May Point the Way to Mending a Broken Heart

Researchers have found that the secret to mending a broken heart — at least at the molecular level — resides within the two-chambered heart of a fish commonly found in household aquariums. The scientists showed that the zebrafish can regenerate its heart after injury, and their studies suggest that understanding cardiac regeneration in this fish may lead to specific strategies to repair damaged human hearts.

Protective protein blocks DNA breaks at fragile sites

With 46 chromosomes and six feet of DNA to copy every time most human cells divide, it’s not surprising that gaps or breaks sometimes show up in the finished product – especially when the cell is under stress or dividing rapidly, as in cancer. But what is surprising is that the breaks don’t always occur at random. They happen at a few specific locations on chromosomes, when cells are under stress, during the stages in the cell cycle where DNA is copied, or replicated, and the cell splits into two identical daughter cells. Scientists call them fragile sites, but the reasons for their inherent instability have remained a mystery. Now researchers have discovered that a protein called ATR protects fragile sites from breaking during DNA replication.

Researchers Identify Cause of Aggressive Childhood Cancer

Researchers have generated a mouse model of a new type of tumor suppressor gene that triggers a rapidly advancing cancer that affects children. The discovery of the fast-onset cancers that result from inactivation of the gene and the technique used to generate the model will likely prove useful in studying genes involved in other forms of cancer.