Protein form and function

Prions are infamous for causing Creutzfeld-Jakob disease, fatal familial insomnia, and bovine spongiform encephalopathy, commonly known as mad cow’s disease. Yet, it’s not likely that’s all they’re good for. Using an unbiased screen in yeast, a team of Whitehead Institute and Stanford University scientists have identified dozens of prion-like proteins that could change the defining characteristics of these unusual proteins. 

Whitehead Institute scientists have developed a method to quickly isolate mitochondria from mammalian cells and systematically measure the concentrations of mitochondrial metabolites. Mitochondrial dysfunction is found in several disorders, including Parkinson’s disease, cardiovascular disease, and mitochondrial diseases. Until now, peering into the inner metabolic workings of these vital organelles has been very challenging.

Using tiny, alpaca-derived, single-domain antibody fragments, Whitehead Institute scientists have developed a method to perturb cellular processes in mammalian cells, allowing them to tease apart the roles that individual proteins play in these pathways. With improved knowledge of protein activity, scientists can better understand not only basic biology but also how disease corrupts cellular function and identify potential therapeutics to rectify these aberrations.

Whitehead Institute researchers have created a map of the DNA loops that comprise the three dimensional (3D) structure of the human genome and contribute to gene regulation in human embryonic stem cells. The location of genes and regulatory elements within this chromosomal framework will help scientists better navigate their genomic research, establishing relationships between mutations and disease development.

The Constitutive Centromere-Associated Network (CCAN) plays a foundational role in the machine that directs chromosome segregation during cell division. On the left is a model of the complete machine (the kinetochore) attached to the microtubule that provides the power for chromosome segregation. The right side depicts the direct interactions between CCAN sub-complexes based on Whitehead scientists’ research as viewed from above the CENP-A nucleosome, either occuring on a single nucleosome (top) or or between two nucleosomes (bottom).”

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.