Editor's Note: Science Scan is a roundup of recently published biotechnology-relevant research.

By taking advantage of techniques developed in the search for treating Alzheimer's disease, researchers have discovered that a molecule called "Notch" is essential for the development of critical kidney cells. Their study, published online and in the Oct. 15, 2003, issue of Development, provides key data about kidney regeneration, which might have implications for tissue regeneration.

Their paper bears the title "g-Secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney." Its senior author is molecular biologist Raphael Kopan at Washington School of Medicine in St. Louis.

"Tissue transplantation is fantastic," observed Kopan, "but it would be so much better if we could instead raise organs from a patient's own cells. Before we can actually trick cells into what we want them to do, we really need to understand every detail about how the organ is put together."

The Notch protein pathway is strongly anti-inflammatory and induces the immune system cytokine TGF-b (transforming growth factor-beta). Using an antibody that specifically identifies the active form of Notch, the co-authors noted that the protein is extremely active in the kidney at an earlier stage than previously thought.

Before proceeding to the mechanism of kidney development, they had to solve a Catch-22 puzzle: How do you study the early lethality effect of Notch in the kidney if animals lacking Notch die before the kidney begins to form? The answer came from far-out left field: Alzheimer's disease (AD). The team discovered that potential AD drugs inhibiting a protein complex called gamma-secretase also interfere with Notch. Such drugs that severely inhibit the protein are ideal for studying its activity in lab animals.

Kopan's team removed both kidneys from normal mice during gestational development and seeded them in organ culture. They treated one kidney from each animal with a gamma-secretase inhibitor and showed that this process prevented all Notch signaling. After three days of secretase inhibition, there were fewer, and less developed, tubular structures in the treated kidneys compared to untreated organs.

Most of the treated cells passed through the first stage of development in which they evolved from embryonic precursor cells into epithelial cells, which form the lining of the organ. But the most pronounced abnormalities occurred in the next developmental stage. Urine forms in the kidney's functional nephrons. Within each of these is a long winding tube, the proximal tubule, and octopus-shaped podocyte cells that wrap their "feet" around blood vessels. After two days of gamma-secretase inhibition, neither podocyte nor proximal tubule cells formed.

"It's as if the cell can tell time," Kopan explained. "After three or four days without Notch signaling, it realizes it will never become a podocyte, and decides to respond to the next signal it receives."

Mammalian Gene Mutations May Finger Human Diseases, As Trail-Blazed By Yellow-Furred Mice

Thanks to canary-colored animal models, a new genetic technique helps pinpoint mutations on specific chromosomes. The method, reported in Nature dated Sept. 4, 2003, is titled "Functional genetic analysis of mouse chromosome 11." Its co-authors are at Baylor College of Medicine in Houston. The reported approach has isolated 230 new recessive mouse mutations, 88 of them on the murine chromosome. The authors express the hope that "this finding will help us understand human gene function and the role of genes in disease." They employed tricks from fruit fly genetics to develop their new mouse screen. The method permits tracking down mutations in a particular region of a particular chromosome. Offspring carrying a mutation sport yellow fur.

Using their strategy, the team spotted a variety of mutations hidden on mouse chromosome 11. They affected skin, nervous system, blood cells, head and faces, plus fertility. An accompanying editorial notes that "the strategy vastly simplifies the breeding and maintenance of mutant strains. No complicated tools, such as molecular genotyping, are required, only the ability to follow coat colors."

"Now that the mouse and human genome sequences are complete," the paper points out, "biologists need systematic approaches to determine the function of each gene. A powerful way to discover gene function is to determine the consequence of mutations in living organisms. Large-scale production of mouse mutations with the point mutagen N-ethyl-N-nitrosurea proved a key strategy for analyzing the human genome because mouse mutants will reveal functions unique to mammals and many may model human diseases."

True To Tradition, Annual Lasker Award Luncheon Ceremony Held At Hotel Pierre In New York City

The 2003 Lasker Awards for Medical Research and Public Service were presented Sept. 19 at a luncheon ceremony in New York City. Guest speakers included Mark McClellan, commissioner of the FDA, and Nicholas Lehmann, new dean of the Columbia School of Journalism. The 2003 Lasker Award for Basic Medical Research was presented to Robert Roeder of the Rockefeller University in New York City for "pioneering studies on eukaryotic RNA polymerases and the general transcription machinery, which opened gene expression in animal cells to biochemical analysis."

The award for Basic Medical Research was shared by Marc Feldmann and Ravinder Maini at the Kennedy Institute of Rheumatology, Imperial College in London. They were cited for their "discovery of anti-[tumor necrosis factor] as an effective treatment for rheumatoid arthritis and other autoimmune diseases."

Often called "America's Nobels," the Lasker Award has been given to 66 scientists who subsequently received the Nobel Prize - including 15 in the last 11 years. Increasingly, the Lasker awardees over the years have come from the biotechnology community.