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

Motor neurons, as the name suggests, are nerve cells that synapse with muscle-movement tissue. Motor neuron disease (MND) attacks motor neurons and causes such fatal neurodegenerative maladies as ALS - amyotrophic lateral sclerosis (Lou Gehrig's disease), as well as Alzheimer's and Parkinson's diseases. No effective therapy exists for any of the motor neuron degenerations. And the underlying defects in more than 98 percent of ALS-type syndromes remain unknown.

A coalition of international research organizations, combining academia and industry, describe a fundamental discovery concerning the genetic and molecular basis for MND. Their report appears in Science dated May 2, 2003, under the title "Mutations in dynein link motor neuron degeneration to defects in retrograde transport." Dynein is a protein involved with mobile structures. It forms "arms" on the outer tubules of cilia and flagella, which propel cells, such as spermatozoa, and functions as a molecular motor.

Of the paper's 38 contributing authors at nine centers, the two principal collaborating institutions are University College in London and Ingenium Pharmaceuticals AG, of Munich, Germany. By identifying two specific mutations in the same gene, the combined research group produced a precise mammalian model of MND and described the pathogenetic link between specific gene mutations and selective progressive degeneration of motor neurons. They began their research with distinct mouse models of MND and traced the genetic cause of their symptoms to point to mutations in a single gene, namely, Dnchc 1.

Based on their discovery, the combined team found that mutations in the Dnchc 1 gene impaired axonal transport in the nerve cell, which specifically caused apoptosis in motor neurons without affecting other cell types. This kind of selective motor neuron degeneration, they noted, is clinically similar on a cellular and organismal level to the human state seen in ALS and other motor neuron diseases.

The co-authors employed N-ethyl-N-nitrosourcea (ENU) as a chemical mutagen to produce random point mutations in the two mouse genomes. They identified a murine phenotype that displayed progressive loss of muscle tone and locomotor ability - in a fashion similar to the ALS progression in humans. Positional cloning located the mutated gene responsible. The findings reported also are important in demonstrating the value of random point mutation research in a model system. Prior studies of this particular gene in knockout animal models produced embryonic lethalities, which carried a targeted disruption of the Dnchc 1 gene. These embryos are not able to sustain post-implantation development, hence no discernible link to MND research.

"The ability to correlate a biological phenotype similar to human disease state with a specific gene mutation," observed Ingenium's CEO and chief scientific officer, Michael Nehls, "is a powerful approach to discovering biological mechanisms that will have real importance in developing new therapeutics."

Gene Chip Spread Plus Human Genome Data Locate 46 Mutations In 182 Colorectal Cancers

An American/Italian set of collaborators identified a family of genes mutated in colorectal cancers. The researchers, at the Johns Hopkins Kimmel Comprehensive Center in Baltimore, state that the discovery is the first of its kind. Their paper is titled "Mutational Analysis of the Tyrosine Kinome [sic] in Colorectal Cancers." It uses microarray technology to profile the genes expressed in a cell, plus data from the human genome, to determine which "tyrosine kinase" genes - hence, "kinome" - were mutated in colorectal cancers.

Tyrosine kinases (TK) are central regulators of signaling pathways that control a wide variety of cellular events, but little has been known about their role in any particular tumor type. The authors discovered 46 mutations in 14 TK genes from a panel of 182 colorectal cancers. Further evidence, they submitted, indicates that these mutations are indeed related to tumor growth, rather than mere coincidence. "This study," the paper stated, "represents the first systematic mutational analysis of any gene family in any human cancer type."

Cultured Adult Human Brain Stem Cells Cured 30 Percent Of Mice Modeling Multiple Sclerosis

Multiple sclerosis (MS) devastates nearly 1 million people worldwide. It subjects them from young adulthood onward to repeated immunological attacks on the brain and spinal cord. MD afflicts twice as many women as men. Its effects vary, depending on where exactly in the nervous system the onslaughts occur. Paralysis, blindness, loss of sensation and a lack of coordination mark the types of MS mayhem wrought by an immune system gone awry.

Injections of cultured adult human brain stem cells helped mice with a form of MS recover from paralysis, as reported in Nature dated April 17, 2003. The paper is titled "Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis."

Its neurological and neurophysiological authors are at the San Raffaele Hospital in Milan, Italy. Their injected stem cells traveled to areas of inflammation in the animals' brains and spinal cords. There they formed new neurons and myelin-producing cells, decreasing the level of inflammatory molecules and cellular scarring in the brain. Up to 30 percent of the mice recovered fully from their hind-leg paralysis and the rest showed considerable improvement. The researchers expressed their hope that, in the future, similar therapies will be used to treat human MS and other autoimmune diseases.

Fewer Calories, Extra Stress And Key Protein Extend Lifespan Of Yeast Cells By 70 Percent

A protein that can lengthen the life of starving, stressed yeast is identified in Nature dated May 8, 2003. The paper is titled "Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae" - baker's yeast. Its authors are pathologists at Harvard Medical School in Boston. Plus their research sheds light on the fundamental mechanisms by which curbing calories can extend the life of many organisms. PNC1 seems to be a key member of a small group of proteins that can fine-tune the lifespan and reproductive capacity of yeast to the quality of the environment.