Technology and methods

Whitehead Institute researchers have identified a potential dual-pronged approach to treating Niemann-Pick type C (NPC) disease, a rare but devastating genetic disorder. By studying nerve and liver cells grown from NPC patient-derived induced pluripotent stem cells (iPSCs), the scientists determined that although cholesterol does accumulate abnormally in the cells of NPC patients, a more significant problem may be defective autophagy—a basic cellular function that degrades and recycles unneeded or faulty molecules, components, or organelles in a cell. Here, the scientists propose two drugs, one to reduce cholesterol buildup and the other to induce autophagy, as a strategy for treating NPC.

Scientists at Whitehead Institute have pinpointed a major mitochondrial pathway that imbues cancer cells with the ability to survive in low-glucose environments. By identifying cancer cells with defects in this pathway or with impaired glucose utilization, the scientists can predict which tumors will be sensitive to these anti-diabetic drugs known to inhibit this pathway.

Since the completion of the Human Genome Project, which identified nearly 20,000 protein-coding genes, scientists have been trying to decipher the roles of those genes. A new approach developed at MIT, the Broad Institute, and the Whitehead Institute should speed up the process by allowing researchers to study the entire genome at once.

Whitehead Institute researchers have used the gene regulation system CRISPR/Cas (for “clustered regularly interspaced short palindromic repeat/CRISPR-associated) to engineer mouse genomes containing reporter and conditional alleles in one step. Animals containing such sophisticated engineered alleles can now be made in a matter of weeks rather than years and could be used to model diseases and study gene function.

Whitehead Institute and MIT chemical engineers and biologists have now devised a way to dramatically boost isobutanol production in yeast, which naturally make it in small amounts. They engineered yeast so that isobutanol synthesis takes place entirely within mitochondria, cell structures that generate energy and also host many biosynthetic pathways.

Using only a computer, an Internet connection, and publicly accessible online resources, a team of Whitehead Institute researchers has been able to identify nearly 50 individuals who had submitted personal genetic material as participants in genomic studies. 

In an approach with the potential to aid therapeutic vaccine development, Whitehead Institute scientists have shown that enzymatically modified antibodies can be used to generate highly targeted, potent responses from cells of the immune system.

Whitehead Institute researchers report that common assumptions employed in the generation and interpretation of data from global gene expression analyses can lead to seriously flawed conclusions about gene activity and cell behavior in a wide range of current biological research.