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Biotechnology

New publications, experiments, and breakthroughs in biotechnology – and what they mean.

Found: A Gene for Diabetes
A common gene variant behind many cases of type 2 diabetes

Source: “Variant of Transcription Factor 7-like 2 (TCF7L2) Gene Confers Risk of Type 2 Diabetes”
S. F. Grant et al.
Nature Genetics 38(3): 320-323

Results: Scientists at deCode Genetics in Iceland identified a gene variant that accounts for more than 20 percent of cases of type 2 diabetes. About 30 percent of Americans carry the gene variant; those who have one copy have a 45 percent greater risk of developing type 2 diabetes, while for those who have two copies (about 7 percent of the U.S. population), the risk is 141 percent greater. The gene, called TCF7L2, regulates the activity of other genes, and the protein it codes for is involved in a biochemical pathway believed to play a role in the maintenance of proper glucose levels.

Why it matters: Scientists have long sought genetic mutations that boost the risk of type 2 diabetes. But the complexity of the disease, which is linked to both environmental and genetic factors, makes the task difficult. The gene identified by deCode is the best genetic predictor of the disease found to date and may point the way to new drug targets.

Methods: DeCode scientists looked at 228 variable genetic markers on a previously identified region of chromosome 10 among 2,000 diabetes patients and controls in Iceland. They identified one version of one marker that correlated with an increased risk of diabetes. They then confirmed the findings in an American and a Danish population.

Next steps: DeCode scientists now plan to develop a genetic test for the variant, which would allow at-risk people to modify their diets and lifestyles long before they develop diabetes. They also plan to search for new drug targets within the biochemical pathway implicated by the gene.

A Curious Clue to Parkinson’s
Drugs that boost protein aggregation could provide a new route to treatment

Source: “Pharmacological Promotion of Inclusion Formation: A Therapeutic Approach for Huntington’s and Parkinson’s Diseases”
Ruth Bodner et al.
Proceedings of the National Academy of Sciences 103(11): 4246-4251

Results: Ruth Bodner, a postdoc at MIT’s Center for Cancer Research, biology professor David Housman, and colleagues have identified a compound that can increase protein aggregation in cellular models of Parkinson’s and Huntington’s disease. When treated with the compound, called B2, Parkinson’s cells that normally would have died survived. And Huntington’s cells treated with the compound had better–functioning proteosomes – the cellular “garbage cans” that are often dysfunctional in the disease.

Why it matters: Abnormal aggregations of protein are a characteristic of many types of neurodegenerative disease, including Huntington’s, Parkinson’s, and Alzheimer’s. However, there is continuing scientific disagreement over the nature of these aggregations. While they correlate with some aspects of the diseases, recent evidence suggests that they may be harmless or even helpful in preventing neuro-toxicity. The MIT study builds on this last possibility by demonstrating that increased protein aggregation can improve the health of cells modeling neurodegenerative disease.

Methods: Scientists conducted a large-scale drug screen, examining how different compounds affected cells that had been engineered to produce mutant proteins implicated in Parkinson’s disease and Huntington’s disease.

Next Step: The MIT researchers conducting the experiments would like to figure out how the B2 compound works. Cells usually get rid of misshapen proteins by breaking them down in proteosomes, but this mechanism may get overloaded in neurodegenerative disease. Housman and Bodner theorize that the compound works by helping the cell sequester into clumps the single proteins or smaller aggregates of proteins that might be harmful to it.

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