WASHINGTON UNIVERSITY, U.S.; Researchers' work from Washington University, U.S., adds to body of knowledge

Researchers' work from Washington University, U.S., adds to body of knowledge.

This trend article about Washington University, U.S., is an immediate alert from NewsRx to identify developing directions of research.

Study 1: New investigation results, "Rationally designed peptides for controlled release of nerve growth factor from fibrin matrices," are detailed in a study published in Journal of Biomedical Materials Research Part A. "The purpose of this research was to identify peptide sequences with varying affinity for nerve growth factor (NGF) and use them in the rational design of affinity-based drug delivery systems. A phage display library (12 amino acid random peptide sequence) was screened against NGF-conjugated chromatography resin three times and fractions containing phage of varying affinity were eluted by decreasing the pH of the eluent," researchers in the United States report.

"These phages were isolated, amplified; then their DNA was purified and sequenced to determine the identity of the random peptide domain. Consensus peptides based on these sequences were synthesized and screened for their ability to bind NGF and release it at different rates from fibrin matrices. The ability of fibrin matrices containing these peptides and NGF to deliver to biologically active NGF was tested using a chick dorsal root ganglia model. A mathematical model was developed to further understand how the affinity of a peptide can modulate release of NGF and to aid in design optimization for the delivery system," wrote S.M. Willerth and colleagues, Washington University, Department of Biomedical Engineering.

The researchers concluded: "The peptides identified in this study were determined to have varying affinities for NGF suggesting that this approach can serve as a model for tailoring the affinity of a drug delivery system for a target protein drug."

Willerth and colleagues published their study in the Journal of Biomedical Materials Research Part A (Rationally designed peptides for controlled release of nerve growth factor from fibrin matrices. Journal of Biomedical Materials Research Part A, 2007;80(1):13-23).

For additional information, contact S.M. Willerth, Washington University, Dept. of Biomedical Engineering, St. Louis, Missouri USA.

Study 2: A new St. Louis-based company will use a novel technology to rapidly screen thousands of drugs for their effectiveness against two of the biggest health threats in the United States - diabetes and cancer.

Ross Cagan, PhD, professor of molecular biology and pharmacology at Washington University School of Medicine in St. Louis and Thomas Baranski, MD, PhD, professor of medicine, will head the new company, Medros Inc. The company's technology can identify drugs with medical benefit by capitalizing on extensive information currently available about fruit fly biology and genetics.

Launched with the joint backing of the School of Medicine and BioGenerator, a nonprofit group formed to help spawn biotech companies from university research, Medros will soon begin operation in the Center for Emerging Technologies in St. Louis.

The company arose from a collaboration between Cagan and Baranski, who is also an endocrinologist at Barnes-Jewish Hospital. Cagan showed Baranski a method developed in his lab for determining if a drug could correct abnormal development in the eyes of fruit flies. Impressed with the concept, Baranski asked if it could be adapted to screen for drugs that could alleviate the complications of diabetes.

"People with diabetes can go blind, their kidneys can fail and their nerves can die," said Baranski. "We don't have any good drugs for counteracting these effects. We know that high blood sugar contributes to these problems, so I went to Ross and asked if his fruit fly system could uncover why high glucose can be toxic."

This challenge led to a full-fledged screening system in which fruit flies, grown from eggs to adults in tiny chambers, serve as indicators of a drug's effect. In this instance, if a fruit fly can grow normally on a high sugar diet in the presence of a particular drug, the drug could potentially lessen the toxicity of high sugar in diabetics, according to Baranski.

Using fruit flies for drug screening is fast and inexpensive because the flies' short life spans and small size allow quick turnaround and multiple simultaneous tests in a small space. Furthermore, the technique determines a drug's effect on the whole organism, not on isolated cells.

"If you start the process of screening drugs by looking at cells in a dish, you miss the effect of drugs on the molecular pathways involved in the whole organism," Cagan said. "For example, metastasis of cancer is actually a response to normal tissue sending a signal to tumor cells telling them to leave the tumor. If you study cancer in a dish, you can't look at that process at all. For decades, researchers have studied cancer this way because it's easy. But that hasn't resulted in significant progress toward a cure."

Cagan and Baranski have developed their screening method to identify drugs effective against metastatic cancer. A simple change in the appearance of specially engineered fruit flies can indicate that a drug may prevent metastasis.

The researchers are confident that their fruit fly model parallels human physiology to a great extent. Molecular pathways that play a role in diabetes and cancer are present in both humans and fruit flies, according to Cagan.

In addition, the researchers feel their approach may be superior to more traditional approaches that go after one disease target, such as a chemotherapeutic drug that aims to influence one gene responsible for cancerous growth.

"With our method, we aren't asking what the target is - we're letting the system tell us," Cagan said. "We're just asking for the bottom line. Do the flies get better? If you find the magic compound that hits everything that contributes to the disease in just the right amount so that the fly can live, then you've made true progress."

Study 3: Scientists have constructed bacterial artificial chromosomes containing HSV-1 strains 17 and KOS.

According to a report from the United States, "Bacterial artificial chromosomes (BACs) were constructed containing full-length, infectious DNA of HSV-1 strains 17 and KOS. To generate BACs without altering viral genes, sequences required for selection and propagation of the BAC were placed between the UL37 and UL38 genes, and flanked by LoxP sites. The system was tested by studying multiple properties of these HSV-1 BAC constructs in vitro and in vivo following propagation in bacteria, virus reconstitution from HSV-BAC DNA in eukaryotic cells, and Cre-recombinase-mediated excision of the BAC backbone."

"Based on in vitro growth in mouse embryo fibroblasts and in vivo growth in mouse corneas and trigeminal ganglia, the strain KOS BAC-derived virus behaved similarly to wild-type," said William W. Gierasch and colleagues at Washington University in St. Louis. "Small changes in neurovirulence were, however, observed. The strain 17 BAC-derived virus exhibited modest decreases in growth and virulence compared to wild-type. Modest differences were observed in reactivation from latency with both strain KOS and 17 BAC-derived viruses. In addition, the system was further validated by performing mutagenesis of the BACs by allelic exchange in E. coli."

"These bacterial artificial chromosomes are suitable for the rapid generation of recombinant viruses for pathogenesis and other studies, but as with all mutagenesis systems, care must be taken in their construction and repair," noted the scientists.

Gierasch and his coauthors published their study in the Journal of Virological Methods (Construction and characterization of bacterial artificial chromosomes containing HSV-1 strains 17 and KOS. J Virol Methods, 2006;135(2):197-206).

For additional information, contact David A. Leib, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Box 8096, 660 South Euclid Avenue, St. Louis, MO 63110, USA. Leib@vision.wustl.edu.

Keywords: St. Louis, Missouri, United States, Herpes Simplex Virus, Bacterial Artificial Chromosomes, Herpesvirus, HSV-1, Proteomics, Recombinant Technology, Virology.

This article was prepared by Hospital Business Week editors from staff and other reports. Copyright 2007, Hospital Business Week via NewsRx.com.