Neurobiology

For the first time, Whitehead Institute scientists have documented a direct link between deletions in two genes—fam57ba and doc2a—in zebrafish and certain brain and body traits, such as seizures, hyperactivity, large head size, and increased fat content. Both genes reside in the 16p11.2 region of the genome, which has been linked to multiple brain and body disorders in humans, including autism spectrum disorder, developmental delays, seizures, and obesity.

Using a novel method, Whitehead Institute researchers have determined how mutations that are not located within genes are identified through genome-wide association studies (GWAS) and can contribute to sporadic Parkinson’s disease, the most common form of the condition. The approach could be used to analyze GWAS results for other sporadic diseases with genetic causes, such as multiple sclerosis, diabetes, and cancer.

Whitehead Institute researchers have created a new mouse-human modeling system that could be used to study neural crest development as well as the modeling of a variety of neural crest related diseases, including such cancers as melanoma and neurofibromatosis. 

Until now, it has been difficult to fully characterize the different structures that proteins can take on in their natural environments. However, using a new technique known as sensitivity-enhanced nuclear magnetic resonance (NMR), Whitehead Institute and MIT researchers have shown that they can analyze the structure that a yeast protein forms as it interacts with other proteins in a cell.

Induced neural stem cells (iNSCs) hold promise for therapeutic transplantation, but their potential in this capacity has been limited by failed efforts to maintain such cells in their multi-potent NSC state. Now, Whitehead Institute scientists have created iNSCs that remain in the multi-potent state—without ongoing expression of reprogramming factors. This allows the iNSCs to self-renew repeatedly to generate cells in quantities sufficient for therapy.

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.

Whitehead Institute scientists have used a yeast cell-based drug screen to identify a class of molecules that target the amyloid-β (Aβ) peptide involved in Alzheimer’s disease (AD).  

Whitehead Institute researchers have determined that the lipid storage disorder Niemann-Pick type C1 (NPC1) disease is caused not only by defects in cholesterol processing but also in autophagy—a key cellular degradation pathway that malfunctions in many neurodegenerative diseases.

A team of researchers from Whitehead Institute and Sanford-Burnham Research Institute has brought new clarity to the picture of how gene-environmental interactions can kill nerve cells that make dopamine. The study uses patient-derived stem cells to show that a mutation in the α-synuclein gene causes increased vulnerability to pesticides, leading to Parkinson’s disease.