Technology and methods

When Whitehead Institute researchers don’t have the tools to answer their questions, they build them.

Whitehead researchers provide insight into a specific gene pathway that appears to regulate the growth, structure, and organization of the human cortex. They also demonstrate that 3D human cerebral organoids--miniature, lab-grown versions of specific brain structures--can be effective in modeling the molecular, cellular, and anatomical processes of human brain development. And they suggest a new path for identifying the cells affected by Zika virus.

Although the genome editing system known as CRISPR/Cas has revolutionized genetic research in cell lines, its overall efficiency has been relatively poor when used to generate genetically altered animals for disease modeling.  Now Whitehead Institute scientists have altered the approach in a manner that could accelerate the production of mice carrying precise mutations of multiple genes.

A team of Whitehead Institute researchers is bringing new levels of efficiency and accuracy to one of the most essential albeit tedious tasks of bench science: pipetting.

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.