COPI Complex Is a Regulator of Lipid Homeostasis
High-throughput screening of small chemicals conducted at the National Institutes of Health (NIH) Chemical Genomics Center (NCGC), administered by the National Human Genome Research Institute (NHGRI), has helped to provide new insights into the way our bodies store fat. Such knowledge may prove valuable in efforts to reduce obesity and treat metabolic disorders.
In a study published in the Nov. 25, 2008 issue of PLoS Biology, a team from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the University of Maryland, Baltimore, and NCGC identified a cellular pathway that regulates fat storage and showed that interrupting the pathway boosts the amount of fat stored by human cells. Continued...
Science News Focus
August 2008 On a mission. Christopher Austin, leader of NIH’s screening center, hopes academics will discover the value of small molecules.
Industrial-Style Screening Meets Academic Biology
Parasitologist David Williams has spent his
career studying Schistosoma, a type of snailborne
worm that kills 280,000 people a year
in the tropics and leaves millions more with
chronic liver and intestinal problems. By
2005, he had found a possible target for a
drug—an enzyme the parasite requires for
survival. But he had no easy way to find a
molecule that would block it. Then he learned
that the U.S. National Institutes of Health
(NIH) was inviting researchers to submit
material to be tested against a huge number of
chemicals to find “hits,” or biological interactions.
Williams applied, was accepted, and
last April, he and collaborators published the
results in Nature Medicine. After screening
71,000 compounds, they found one, Compound
9, that inhibits the enzyme and killed at
least 90% of the worms in schistosomeinfected
mice.
Continued...
James Inglese: Uniting Biology and Chemistry in High Throughput.
Ever since the Human Genome Project was completed in 2003, scientists have been at odds over how best to unlock the potential for translational research encoded in the newly sequenced 20,000-odd genes. For James Inglese, Ph.D., the answer is simple: to solve this tough biological problem, look to chemistry. As deputy director of the National Institutes of Health Chemical Genomics Center (NCGC), Inglese and his colleagues use highthroughput screening (HTS) to help other investigators identify small molecules that
might make novel and effective tools for studying proteins, cellular functions, and biological processes involved in physiology or disease. After winding his way from academic
laboratories to small biotech and big pharma, Inglese uses his unique perspective to guide a team of about 50 scientists, helping them to develop powerful and efficient assays and to make the most of HTS
hits through chemistry optimization. These efforts, provided as a government-funded resource for researchers selected several times a year from around the world, expand the options for small academic laboratories and biotech firms... Continued...
Natasha Thorne: ACS Chemical Biology author profile
I'm a postdoctoral fellow at the NCGC, and the foundation of my research is largely translational, ultimately helping to make high throughput screening (HTS) and chemical probe discovery and development accessible to basic researchers. Some of my projects are collaborations with academic laboratories and involve the development and optimization of biological assays for HTS, which we use as a method to identify biologically active chemical probes.
Continued...
Further Reading: Original ACS Chemical Biology article describes the finding that luciferase inhibitors can stabilize reporter levels in cell-based HTS assays which can mistakenly be attributed to gene or pathway activation.
Research Findings Open New Front in Fight against AIDS Virus Human Protein May Offer Novel Target for Blocking HIV Infection
Bethesda, Md., Mon., April 28, 2008 — A research group supported by the National Institutes of Health (NIH) has uncovered a new route for attacking the human immunodeficiency virus (HIV) that may offer a way to circumvent problems with drug resistance. In findings published today in the online edition of the Proceedings of the National Academy of Sciences, the researchers report that they have blocked HIV infection in the test tube by inactivating a human protein expressed in key immune cells. Continued...
Further Reading: PNAS Selective targeting of ITK blocks multiple steps of HIV replication
Scientists Identify New Leads for Treating Parasitic Worm Disease Compounds May Provide Much-Needed New Weapons in Worldwide Battle Against Schistosomiasis
Bethesda, Md., Sun., Mar. 16, 2008 — A research team supported by the National Institutes of Health (NIH) Roadmap and the National Institute of Allergy and Infectious Diseases (NIAID) has identified chemical compounds that hold promise as potential therapies for schistosomiasis, a parasitic disease that afflicts more than 200 million people worldwide. The findings were reported today in the advance online publication of the journal Nature Medicine. Continued...
NIH Collaborates with EPA to Improve the Safety Testing of Chemicals New Strategy Aims to Reduce Reliance on Animal Testing
Bethesda, Md., Feb.14, 2008 — Testing the safety of chemicals ranging from pesticides to household cleaners will benefit from new technologies and a plan for collaboration, according to federal scientists from the National Institutes of Health (NIH) and the U.S. Environmental Protection Agency (EPA), who today announced a new toxicity testing agreement. The concept behind this agreement is highlighted in the Feb. 15, 2008 issue of the journal Science.
"I launched the NIH Roadmap for Medical Research five years ago to create collaborations between institutes and centers on big projects that none of them could do alone. But I never envisioned a trans-agency collaboration testing for environmental toxins," said NIH Director Elias A. Zerhouni, M.D. "This research collaboration has the potential to make crucial discoveries that will protect the public health by identifying and understanding chemical toxicants to which people are exposed." Continued...
Finding What's Toxic Fast NCGC Lends Its Technology to Modernizing Toxicity Screening, Refining Animal Testing
Chemical compounds — from household cleaners to pesticides — require testing to reveal hazards that they may pose to human health.
An effort now underway by three collaborating federal research groups seeks to rapidly evaluate larger numbers of chemicals for risks to humans while reducing the role of laboratory animals in regulatory testing. Continued...
Transforming Environmental Health Protection
Collins FS, Gray GM, Bucher JR. Science, , Feb. 15, 2008
We propose a shift from primarily in vivo animal studies to in vitro assays, in vivo assays with lower organisms, and computational modeling for toxicity assessments. Continued...
